Fast hypothermia induced by extracorporeal circuit cooling alleviates renal and intestinal injury after cardiac arrest in swine

BackgroundContinuous renal replacement therapy (CRRT) was currently demonstrated to be an effective way to induce fast hypothermia and had proective effects on cardiac dysfunction and brain damage after cardiac pulmonary resuscitation (CPR). In the present study, we aimed to investigate the influence of extracorporeal circuit cooling using CRRT on renal and intestinal damage after CPR based on a porcine model.Methods32 pigs were subjected to ventricular fibrillation for 8 min, followed by CPR for 5 min before defibrillation. All were randomized to receive extracorporeal circuit cooling using CRRT (CRRT, n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (n = 5) at 5 min post resuscitation. Pigs in the CRRT group were cooled by 8-h CRRT cooling with the infusion line initially submerged in 4 °C of ice water and 16-h SC, while in the SC group by a 24-h SC. Temperatures were maintained at a normal range in the other two groups. Biomarkers in serum were measured at baseline and 1, 3, 6, 12, 24 and 30 h post resuscitation to assess organ functions. Additionally, tissues of kidney and intestine were harvested, from which the degree of tissue inflammation, oxidative stress, and apoptosis levels were analyzed.ResultsThe blood temperature decreased faster by extracorporeal circuit cooling using CRRT than SC (9.8 ± 1.6 vs. 1.5 ± 0.4 °C/h, P < 0.01). Post-resuscitation renal and intestinal injury were significantly improved in the 2 hypothermic groups compared to the NT group. And the improvement was significantly greater in animals received extracorporeal circuit cooling than those received surface cooling, from both the results of biomarkers in serum and pathological evidence.ConclusionFast hypothermia induced by extracorporeal circuit cooling was superior to.surface cooling in mitigating renal and intestinal injury post resuscitation.     

富硒当归治疗慢性肾衰竭的疗效及对患者微炎症状态的影响

目的研究富硒当归治疗慢性肾衰竭的疗效及对患者微炎症状态的影响。方法选取2014年3月至2015年3月该院接诊的80例慢性肾衰竭患者作为研究对象。按照随机数表法分为观察组和对照组,每组各40例。对照组采用常规治疗,观察组采用常规加富硒当归治疗,观察2组患者治疗前后肾功能指标血尿素氮(BUN)、血肌酐(SCr)、血红蛋白(Hb)的水平变化,微炎症状态中C反应蛋白(CRP)、白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α水平变化,中医证候积分,治疗疗效情况。结果治疗后,观察组BUN、SCr均小于对照组[(16.08±3.29)mmol/L与(21.50±3.68)mmol/L,(330.21±81.96)μmol/L与(390.86±84.24)μmol/L],Hb高于对照组[(107.38±7.37)g/L与(98.27±6.36)g/L](P0.05);观察组CRP、IL-6、TNF-α均小于对照组[(5.92±1.14)mg/L与(7.26±2.02)mg/L,(24.75±7.12)pg/mL与(41.08±9.07)pg/mL,(112.16±20.16)ng/L与(134.46±22.16)ng/L],差异有统计学意义(P0.05)。治疗后观察组中医证候积分小于对照组[(5.01±1.21)分与(9.36±2.43)分],差异有统计学意义(P0.05)。观察组总有效率优于对照组[95.00%(38/40)与75.00%(30/40)],差异有统计学意义(P0.05)。结论富硒当归治疗慢性肾衰竭的疗效显著,能够有效地改善患者微炎症状态,能够提高疗效。     

Prevalence of different forms of infarct-atypical late gadolinium enhancement in patients early and late after heart transplantation

Background

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) enables high-resolution myocardial tissue characterization, showing the results of different injuries, especially in the early period after heart transplantation (HTX).

Objectives

We sought to apply LGE-CMR to investigate the prevalence and patterns of infarct-atypical myocardial involvement and associated mechanisms in patients early and late after HTX.

Methods

LGE-CMR was performed on a 1.5-T MRI scanner (Philips, Best, the Netherlands) in 89 patients: group 1 (48 patients) less than 2.5 years after operation (1.2 ± 0.5 years) and group 2 (41 patients) later this period (8.2 ± 4.2 years). Following LGE-CMR, the presence, distribution, patterns of infarct-atypical LGE and possible associated mechanisms were assessed.

Results

71 % of group 1 patients (34/48) showed infarct-atypical LGE whereas 57 % of group 2 patients (22/41) were affected (p = 0.25). Fewer segments/patients were involved later after HTX (1.6 ± 2.0 vs. 2.9 ± 3.1 segments/patient; p = 0.03), but only diffuse LGE-CMR pattern decreased significantly (11.5 % of affected segments in group 1 vs. 6.5 % in group 2; p < 0.001). Group 2 had lower ischemic time (181 ± 53 vs. 208 ± 61 min; p = 0.03), the donors were younger (33 ± 13 vs. 41 ± 13 years; p = 0.01) and fewer donors were Toxoplasma gondii seropositive (4 vs. 22pts; p < 0.001).

Conclusion

Infarct-atypical LGE was found in a significant number of patients early post-HTX, however, fewer patients and myocardial segments per patient were affected later after HTX. Many potential factors seem to be involved, but the exact mechanisms are still unclear. Future studies are necessary to test prognostic implications associated with LGE-CMR patterns.     

Anemia Control in Renal Transplant Recipients Receiving Continuous Erythropoietin Receptor Activator (C.E.R.A.) Treatment: The AnemiaTrans Study

Introduction

Continuous erythropoietin receptor activator (C.E.R.A.) effectively enables anemia control in patients with chronic kidney disease, but little information is available in renal transplant recipients. The authors aimed to evaluate the effect of C.E.R.A. under clinical practice conditions on anemia control in renal transplant recipients.

Methods

This was a multicenter, retrospective, observational study carried out in adult renal transplant patients in the immediate posttransplant period and at late posttransplant period receiving C.E.R.A. in clinical practice. Patients?? data were retrieved from their medical charts at baseline and months 1, 3, and 6.

Results

A total of 318 evaluable patients were enrolled into the study: 32 in the immediate posttransplant period and 286 at late posttransplant period (erythropoiesisstimulating agent [ESA]-na?ve, n = 44; converting from other ESAs, n = 242). Patients in the immediate posttransplant period experienced a significant increase in hemoglobin (Hb) levels from baseline to month 1 (9.9±1.5 g/dL vs. 11.5±1.4 g/dL; P< 0.001). ESA-na?ve patients showed increasing mean Hb levels from baseline to month 6 (10.1±0.7 g/dL vs. 11.7±1.0 g/dL; P < 0.001) and 94.7% achieved Hb ??11 g/dL during the study. In patients converted from other ESAs, the percentage of patients with Hb between 11?C13 g/dL was maintained from baseline to month 6 with no significant differences (61.0% vs. 62.4%). Mean monthly doses of C.E.R.A. at baseline were 134.4±56.4 ??g, 81.3±28.1 ??g, and 93.0±44.2 ??g in immediate posttransplant, ESA-na?ve, and converted patients, respectively. C.E.R.A. was well tolerated.

Conclusion

C.E.R.A. enables anemia control in renal transplant recipients, allowing target Hb levels to be achieved and maintained with doses even below those described in the Summary of Product Characteristics.     

Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis in rats

The purposes of this study were to determine the tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on cytokine production. Methods: acute pancreatitis was induced by the retrograde injection of 200 βl taurocholic acid into the pancreatic duct in male Wistar rats. The serum amylase activity, the wet pancreatic weight/body weight ratio, and the TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed 6, 24, 48 or 72 h after the operation. Results: the TNF bioassay revealed high levels of TNF (30.2±5.4 U/ml, 35.0±5.0 U/ml and 36.6±6.0 U/ml) in the control group at 6, 24 and 48 h and (54.1±20U/ml and 10.9±4.2 U/ml) in the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased levels in the pentoxifylline-treated group at 48 h (7083±2844 pg/ml, 6463±1307 pg/ml, 10329±5571 pg/ml vs 137.5±85.5 pg/ml, respectively, P <0.05). The high mortality observed in the pancreatitis group (43%) was decreased by pentoxifylline administration to 11%. Conclusion: these results demonstrate that pentoxifylline very effectively inhibits cytokine production in acute pancreatitis.     

25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment

Background

Vitamin D deficiency is nowadays considered as a potential cardiovascular and renal risk factor. We tested the hypotheses that vitamin D deficiency impairs the endothelial function of renal vasculature and whether vitamin D levels and endothelial function can be improved by the treatment with statins.

Methods

In a double-blind, randomized study of 31 hypercholesterolemic patients with vitamin D insufficiency (<30 ng/ml) were randomly assigned to rosuvastatin (10 mg/d) and placebo for 6 weeks. Basal nitric oxide (NO) activity of the renal vasculature was assessed both before and after the blockade of NO synthases with systemic infusion of N(G)-monomethyl-l-arginine (l-NMMA). In parallel, 25(OH)D was measured.

Results

Multiple regression analysis revealed that at baseline 25(OH)D is an independent determinant of basal NO activity as assessed by the decrease in RPF, in response to l-NMMA (β = ?0.446, r = 0.015). Compared to placebo treatment, rosuvastatin increased 25(OH)D levels (21.6 ± 4.0 vs. 24.1 ± 8.1 ng/ml, p = 0.039). Basal NO activity was significantly more increased after 6-week therapy with rosuvastatin than with placebo (?94.8 ± 70 vs. ?68.2 ± 32 ml/min, p = 0.044), indicating increased basal NOS activity after 6 weeks of rosuvastatin treatment. Basal NO activity in the placebo phase was correlated inversely with 25(OH)D (r = ?0.385; p = 0.027).

Conclusions

Thus, vitamin D insufficiency is associated with impaired endothelial function in the renal vasculature and both were beneficially influenced by the treatment with rosuvastatin.     

The nitura study — effect of nitroglycerin or urapidil on hemodynamic, metabolic and respiratory parameters in hypertensive patients with pulmonary edema

Objective: To assess the effects of nitroglycerin or urapidil on hemodynamic, respiratory and metabolic parameters in hypertensive patients with pulmonary edema. Design: Open, randomized and prospective clinical study. Setting: Out-of-hospital setting and Emergency Department in a 2000-bed hospital. Patients: Hundred twelve patients with evidence of hypertensive crises with pulmonary edema (systolic blood pressure (SBP) >200 mmHg and/or diastolic blood pressure (DBP) >100 mmHg and rales over both lungs) at the time when the emergency physician arrived. Interventions: The out-of-hospital treatment consisted of oxygen via face mask, 80 mg furosemide i. v., 10 mg morphium s. c., and either nitroglycerin sublingually (initial dose: 0.8 mg; repetitive administration of 0.8 mg every 10 min to a cumulative dose of 3.2 mg) or urapidil (initial dose: 12.5 mg i.v.; repetitive administration every 15 min to a cumulative dose of 50 mg). If SBP was more than 180 mmHg and/or DBP more than 90 mmHg on admission, antihypertensive treatment was continued with nitroglycerin (0.3–3 mg/h) or urapidil (5–50 mg/h). Measurements and results: Blood pressure (BP) was measured every 5 min with the use of an automatic oscillometric device. Serum lactate, PO₂, pH value, and base excess (BE) were evaluated on admission and 6 h later. Blood pressure, serum lactate and BE on admission were significantly lower (SBP: 155±30 vs 179±33 mmHg; p=0.0002; DBP: 82±17 vs 93±19 mmHg; p=0.001; lactate: 2.2±1.6 vs 3.9±2.7; p=0.0001; BE: ?1.9±3.9 vs ?4.4±1.7; p=0.0005) and PO₂ and pH values were significantly higher in the urapidil group compared to the nitroglycerin group (PO₂: 75±25 vs 66±17; p=0.036; pH: 7.33±0.08 vs 7.29±0.09; p=0.042). After 6 h no differences between the two groups were observed. Conclusion: The more pronounced BP reduction in the urapidil group was associated with an improved respiratory and metabolic situation in hypertensive patients with pulmonary edema. Therefore, urapidil is a valuable alternative to nitroglycerin in patients with pulmonary edema and systemic hypertension.     

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2±1.5 pg/ml) was significantly higher (P<0.05) than in pretransplantation samples (3.2±0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8±5.9 mg/dl, which was significantly higher than before transplantation (6.4±2.2 mg/dl). There was a positive correlation between the serum BUn and ET-1 (r=0.62,P<0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9±32.4%) than with those obtained before transplantation (18.3±9.2%) when compared to a standard contractility rate of 100% with 40 mM KCl. Moreover, these contractility response rates were significantly reduced (32.8±21.0%) with the addition of the ET-1 receptor antagonist FR139 317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.     

Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs

We previously showed a beneficial effect of hemofiltration on hemodynamics of endotoxic shock pigs. To test the hypothesis that this effect of hemofiltration is caused by convective removal of factors that adversely effect hemodynamics during endotoxemia, we infused ultrafiltrate from endotoxic shock pigs into healthy pigs. Their hemodynamics were compared with those of pigs who were infused with ultrafiltrate from healthy pigs. Twelve anesthetized and ventilated pigs were hemodynamically monitored for 150 minutes following the infusion of 2 L of ultrafiltrate from 12 donor pigs. The acceptor pigs were randomly divided into two groups; group 1 received ultrafiltrate from pigs who were hemofiltered after the infusion of 0.5 mg/kg endotoxin over 30 minutes; group 2 served as a control group, receiving ultrafiltrate from healthy donor pigs. Group 1 showed a decrease in mean arterial pressure of 28 ± 7 mm Hg (mean ± SEM) versus an increase of 17 ± 3 mm Hg in group 2 (P < .04). Mean pulmonary artery pressure increased more in group 1 than in group 2 (9 ± 2 mm Hg versus 1 ± 1 mm Hg, P < .04). The decrease in cardiac output in group 1 was greater than in group 2 (3.3 ± 0.2 L/ min v 0.3 ± 0.3 L /min, P < .02) and was due to a decrease in stroke volume. The decrease in right ventricular ejection fraction was also greater (0.15 ± 0.02 v 0.01 ± 0.00, P < .01). Systemic vascular resistance, right atrial pressure, right ventricular end-diastolic volume, pulmonary wedge pressure and heart rate did not differ between groups. In contrast to ultrafiltrate from healthy pigs, ultrafiltrate from endotoxic shock pigs contains soluble, filtrable factors that increase pulmonary artery pressure and depress cardiac performance.     

Urine activity of cathepsin B,collagenase and urine excretion of TGF-β 1 and fibronectin in membranous glomerulonephritis

In 30% of cases nephrotic syndrome is caused by membranous glomerulonephritis (MG). Protein accumulation in glomeruli leads to progressive loss of kidney function and damage of structure in MG. The role of tissue proteolytic systems and growth factors in this process is not known. The purpose of the study was to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-β ₁ and fibronectin in MG. Cathepsin B activity was greater in the urine of MG patients than in the control group (10.58±8.73 pmol AMC/mg creatinine per min^?1 vs control 7.11±2.05 pmol AMC/mg creatinine per min^?1; P<0.05). Urine collagenase activity was higher in the group of patients than in the control group (8.59±4.26 pmol AMC/ mg creatinine per min^?1 vs control 3.84±2.09 pmol AMC/ mg creatinine per min^?1 P<0.02). Urine excretion of fibronectin (45.60 ng/mg creatinine vs control 10.30 ng/mg creatinine; P<0.04) and TGF-β ₁ levels in the urine were higher than in controls (283.55±248.13 pg/ml vs 36.11±48.01 pg/ml; P<0.01). Results suggest glomerular overproduction of TGF-β ₁ and urinary leak of proteolytic enzymes (PE). This may result in decreased glomerular PE activity in MG and, with time, may lead to protein accumulation in renal glomeruli and to progressive loss of kidney function and damage of structures as the course of MG progresses. PE urine composition as well as ECM protein and cytokine urine excretion may alow noninvasive glomerulopathy course monitoring in humans in the future.     

Induced brain hypothermia in asphyxiated human newborn infants: a retrospective chart analysis of physiological and adverse effects

Objective: To assess the physiological effects and adverse side-effects of induced hypothermia in asphyxiated newborn infants as a base for future controlled, randomized trials.¶Design: Retrospective chart analysis with historical controls.¶Setting: Tertiary neonatal intensive care unit of the University of Cape Town, South Africa.¶Patients: Twenty-one asphyxiated newborns treated with induced hypothermia between September 1997 and February 1998 were compared to 15 asphyxiated newborn infants admitted during March to August 1997. The two groups of infants did not differ in patient characteristics or severity of asphyxia (comparison group vs hypothermia group: Apgar at 5 min 5.3 ± 3.1 vs 5.2 ± 2.3; base deficit 15.6 ± 6.3 vs 11.5 ± 7.2 and Thompson neurological score 10.1 ± 4.0 vs 9.1 ± 3.6).¶Interventions: Hypothermia was induced by placing a cap formed from coolpacks, at a temperature of about 10 °C, around the head of asphyxiated newborn infants to maintain the nasopharyngeal temperature between 34 and 35 °C. Hypothermia was maintained for 3 days.¶Measurements and results: In the comparison group 4/15 infants died and in the hypothermia group 4/21 died. Hypothermia was induced at a median of 6.0 h (range 45 min to 53 h) post-partum, maintained for an average of 80 h (median 77.5 h, range 22 to 185 h) and resulted in an average nasopharyngeal temperature of 34.6 ± 0.5 °C. Hypothermia reduced abdominal skin temperature from 36.3 ± 0.5 °C to 35.1 ± 0.35 °C (p = 0.0001), heart rate from 139 ± 21 to 121 ± 13 beats/min (p < 0.0001) and respiratory rate from 67 ± 11 to 56 ± 9 breaths/min (p = 0.005). Neither episodes of bradycardia nor dysrhythmias, apnea, clinical signs of bleeding diathesis in the hypothermia group nor differences in the frequency of hypoglycaemia and urinary output, blood in urine or tracheal secretion between the two groups were observed. In the survivors the neurological score, assessed at day 2 and day 5, fell from 10.9 ± 3.5 to 8.1 ± 4.5 in the hypothermia group and rose from 8.1 ± 2.5 to 9.0 ± 3.1 in the comparison group (p = 0.003).¶Conclusions: Adverse effects of mild hypothermia induced for 3 days in asphyxiated newborns were significantly less than expected from previous reports on neonates with accidental hypothermia.     

Can Viscoelasticity Measurements Obtained Through Shear-Wave US Elastography be used to Monitor Hepatic Ischemia-Reperfusion Injury and Treatment Response? An Animal Study

This study aimed to investigate whether viscoelasticity measurements can be used to quantitatively analyze and monitor therapy response in hepatic ischemia-reperfusion injury (HIRI). All animals were divided into three groups: a sham operation group (n = 12), an ischemia-reperfusion injury (IRI) group (n = 12) and an andrographolide pre-treatment group (n = 6). To assess the feasibility of using shear-wave velocity (SWV) and shear-wave dispersion (SWD), shear-wave ultrasound elastography was applied onto IRI rats after 4 and 24 h of reperfusion or sham operation (each time point subgroup n = 6). For the verification experiments, six additional rats received andrographolide injection 2 h before IRI and were examined 24 h after reperfusion. The rats were sacrificed for biochemical and histopathological analyses after ultrasound scanning was performed. Compared with the sham group, the IRI group exhibited significantly higher SWD after both 4 and 24 h of reperfusion（10.69 ± 0.69 vs. 15.20 ± 3.23 and 9.01 ± 0.46 vs. 19.35 ± 0.86; p < 0.05). A positive correlation was found between SWD values and Suzuki’s score (r = 0.621; p < 0.05). No correlation was found between SWV and Suzuki’s score (r = 0.283; p > 0.05), although significant differences were found between the two groups after 24 h of reperfusion. Andrographolide treatment resulted in a significantly decreased SWD (15.24 ± 0.45 vs. 19.35 ± 0.86; p < 0.05), whereas SWV showed no statistically significant difference. This study demonstrated the potential of using viscoelasticity measurements for the diagnosis and therapeutic monitoring of HIRI, and that the use of SWD was significantly more advantageous than SWV.     

Incidence and characterization of acute kidney injury after acetaminophen overdose

PurposeAcute kidney injury (AKI) occurs in 2–10% of patients with acetaminophen (APAP) overdose. Elevation in creatinine (SCr) typically occurs 2 to 5 days after ingestion, with a mean peak on day 7, and normalization over a month. However, it remains unclear whether renal impairment occurs without hepatotoxicity. We hypothesized that APAP-associated acute renal failure occurs in patients with and without severe liver dysfunction after APAP overdose.Materials and methodsWe retrospectively evaluated all patients admitted to the Medical Intensive Care Unit at a tertiary hospital and received acetylcysteine between June 2009 and December 2014. Of the 303 patients meeting these criteria, 139 of these patients received acetylcysteine for APAP overdose. Of these patients, 138 had Model for End-Stage Liver Disease (MELD) Scores on Day 1 of admission. Using a modified MELD (m-MELD) score, only containing total bilirubin and international normalized ratio not the SCr, the median m-MELD score was calculated. Patients with m-MELD scores below the median were compared to those with scores above the median (low m-MELD score <2.9 or high m-MELD score >2.9).ResultsBaseline demographics were similar in the two groups with the exception of more hypertension in the low m-MELD group (24 vs 7%; P= .02). Time to admission was shorter in the low m-MELD group (7.9 ± 9.3 vs. 25.7 ± 29.2 hours; P= .001). The mean admission APAP level was 96.9 (±119) μg/mL in the low compared to 52.3 (±85.3) μg/mL in the high m-MELD group (P= .012). Day one SCr (1.2 ± 0.9 vs 2.7 ± 2.2 mg/dL; P< .0001) and change from baseline to highest SCr (0.2 ± 0.3 vs. 2.7 ± 3.3 mg/dL; P< .0001) were both lower in the low m-MELD group compared to the high m-MELD group. In addition, renal failure resolved upon discharge in all 2 patients (3%) with AKI in the low m-MELD group as compared to only 19 patients (44%) in the high m-MELD group.ConclusionsMean day one SCr, maximum change in SCr, and lack of renal failure resolution were higher in patients with higher m-MELD scores. However, patients with low m-MELD scores presented much earlier than patients with high m-MELD scores and 26% developed AKI.     

Effects of a 12-week home-based exercise program on the level of physical activity, insulin, and cytokines in colorectal cancer survivors: a pilot study

Purpose

The purposes of this study are to examine (1) the feasibility and efficacy of two different home-based exercise protocols on the level of physical activity (PA), and (2) the effect of increased PA via home-based exercise program on biomarkers of colorectal cancer.

Methods

Seventeen patients (age 55.18 ± 13.3 years) with stage II–III colorectal cancer completed the 12-week home-based exercise program. Subjects were randomized into either casually intervened home-based exercise group (CIHE) or intensely intervened home-based exercise group (IIHE). The primary outcome was the level of PA. Furthermore, insulin, homeostasis model assessment of insulin resistance, insulin-like growth factor axis, and adipocytokines were measured.

Results

Both CIHE and IIHE program significantly increased the level of PA at 12 weeks compared to its level at baseline (CIHE, 10.00?±?8.49 vs. 46.07?±?45.59; IIHE, 12.08?±?11.04 vs. 35.42?±?27.42 MET hours per week). Since there was no difference in PA change between groups (p?=?0.511), the data was combined in analyzing the effects of increased PA on biomarkers. Increase in PA significantly reduced insulin (6.66?±?4.58 vs. 4.86?±?3.48 μU/ml, p?=?0.006), HOMA-IR (1.66?±?1.23 vs. 1.25?±?1.04, p?=?0.017), and tumor necrosis alpha-α (TNF-α 4.85?±?7.88 vs. 2.95?±?5.38 pg/ml, p?=?0.004), and significantly increased IGF-1 (135.39?±?60.15 vs. 159.53 ng/ml, p?=?0.007), IGF binding protein (IGFBP)-3 (2.67?±?1.48 vs. 3.48?±?1.00 ng/ml, p?=?0.013), and adiponectin (6.73?±?3.07 vs. 7.54?±?3.96 μg/ml, p?=?0.015).

Conclusion

CIHE program was as effective as IIHE program in increasing the level of PA, and the increase in PA resulted in significant change in HOMA-IR, IGF-1 axis, TNF-α, and adiponectin levels in stage II–III colorectal cancer survivors.     

Anti‐inflammatory effect of 4‐methylcyclopentadecanone in rats submitted to ischemic stroke

This study aimed to investigate the anti‐inflammatory effect of 4‐methylcyclopentadecanone (4‐MCPC) in rats suffering from a cerebral ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4‐MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF‐α and IL‐1β levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF‐κB p65 subunit and expression of p‐IκBα were investigated by Western blotting. Our results showed that 4‐MCPC treatment decreased infarct volume significantly, compared with I/R group (16.8%±7.5% vs. 39.7%±10.9%); it reduced MPO activity (0.43 ± 0.10 vs. 1.00 ± 0.51 U/g) and expression levels of TNF‐α (18.90 ± 3.65 vs. 35.87 ± 4.87 ng/g) and IL‐1β (1.68 ± 0.23 vs. 2.67 ± 0.38 ng/g) in ischemic brain tissues of rats. Further study revealed that 4‐MCPC treatment markedly reduced nuclear translocation of NF‐κB p65 subunit and expression of p‐IκBα in ischemic cerebral cortex. Taken together, our results suggest that 4‐MCPC protects against cerebral I/R injury and displays anti‐inflammatory actions through inhibition of the NF‐κB signal pathway.     

Feasibility of dynamic CT-based adenosine stress myocardial perfusion imaging to detect and differentiate ischemic and infarcted myocardium in an large experimental porcine animal model

The purpose of the study is feasibility of dynamic CT perfusion imaging to detect and differentiate ischemic and infarcted myocardium in a large porcine model. 12 Country pigs completed either implantation of a 75 % luminal coronary stenosis in the left anterior descending coronary artery simulating ischemia or balloon-occlusion inducing infarction. Dynamic CT-perfusion imaging (100 kV, 300 mAs), fluorescent microspheres, and histopathology were performed in all models. CT based myocardial blood flow (MBF_CT), blood volume (MBV_CT) and transit constant (K_trans), as well as microsphere’s based myocardial blood flow (MBF_Mic) were derived for each myocardial segment. According to histopathology or microsphere measurements, 20 myocardial segments were classified as infarcted and 23 were ischemic (12 and 14 %, respectively). Across all perfusion states, MBF_CT strongly predicted MBF_Mic (β 0.88 ± 0.12, p < 0.0001). MBF_CT, MBV_CT, and K_trans were significantly lower in ischemic/infarcted when compared to reference myocardium (all p < 0.01). Relative differences of all CT parameters between affected and non-affected myocardium were higher for infarcted when compared to ischemic segments under rest (48.4 vs. 22.6 % and 46.1 vs. 22.9 % for MBF_CT, MBV_CT, respectively). Under stress, MBF_CT was significantly lower in infarcted than in ischemic myocardium (67.8 ± 26 vs. 88.2 ± 22 ml/100 ml/min, p = 0.002). In a large animal model, CT-derived parameters of myocardial perfusion may enable detection and differentiation of ischemic and infarcted myocardium.     

Vancomycin assay performance in patients with acute renal failure

Objective: Fluorescence polarization immunoassays (FPIA) have been reported to overestimate vancomycin serum concentrations compared to high-performance liquid chromatography (HPLC) or enzyme multiplied immunoassay technique (EMIT) in patients with chronic renal disease. The assay manufacturer has modified the FPIA to remedy this overestimation. The purpose of this study was to compare the assay performance of two FPIAs to EMIT in acute renal failure patients receiving vancomycin and continuous venovenous hemofiltration.¶Design: Open-label trial.¶Setting: Intensive care unit in a university affiliated hospital.¶Patients and participants: 15 serum and ultrafiltrate samples were obtained from 14 critically ill patients (mean ± SD; 57 ± 12 years; 8 males/6 females).¶Measurements and results: Vancomycin concentrations were determined by a polyclonal FPIA (pFPIA) performed on the TDx system, a monoclonal FPIA (mFPIA) performed on the AxSYM system and EMIT. The coefficient of variation for all assays was < 5 %. The mean difference ± SD_d between mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: –0.08 ± 1.55 and 1.24 ± 2.11 mg/l, respectively. The limits of agreement between the mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: –3.18 to 3.03 and –2.99 to 5.46 mg/l, respectively.¶Conclusions: Our data demonstrate that the manufacturer's changes to the pFPIA have reduced overestimation. The mFPIA appears to be an acceptable assay for measuring vancomycin serum concentrations in acute renal failure patients and does not significantly overestimate these concentrations.     

Mri quantification of left ventricular function in microinfarct versus large infarct in swine model

To quantify, using MRI, the acute impacts of defined volume and sizes of coronary microemboli on myocardial viability and left ventricular (LV) function and to use LAD occlusion/reperfusion, as a reference. A total of 28 farm pigs were used in this study. Eight animals were used as controls. Successful coronary interventions were performed under X-ray fluoroscopy in 16 pigs to induce microinfarct (delivery of 16 mm³ of 40–120 μm) and large infarct (90 min LAD occlusion/reperfusion). On day 3, animals were imaged using contrast enhanced (in beating and non-beating hearts) and cine MRI for evaluating LV viability and function, respectively. Microscopy and cardiac injury enzymes were used to confirm the presence of necrosis. Myocardial damage was smaller after microembolization than occlusion/reperfusion (6.5 ± 0.6 %LV mass vs. 12.6 ± 1.2 %, P < 0.001). The increase in LV end-systolic volume and decreases in ejection fraction, cardiac output and regional systolic wall thickening, however, were comparable between groups, but significantly differed from controls. MRI also demonstrated microvascular obstruction after microembolization and occlusion/reperfusion as hyperenhanced and hypoenhanced regions, respectively. Microscopic examination revealed patchy necrosis, inflammatory cell infiltration, but no intramyocardial hemorrhage after microembolization and extensive intramyocardial hemorrhage and transmural damage in the occlusion/reperfusion group. Cardiac injury enzymes confirmed presence of myocardial damage in animals with interventions. Coronary microemboli have acute impact on LV function compared to control animals. Despite the difference in myocardial damage, global and regional LV dysfunction after microembolization was comparable to occlusion/reperfusion. This MR study suggests that the pattern of myocardial damage plays a role in LV dysfunction.     

Meal Ingestion and Hemodynamic Interactions Regarding Renal Blood Flow on Duplex Sonography: Potential Diagnostic Implications

Splanchnic blood flow changes dramatically after meal ingestion. The present study evaluated physiologic interactions between meal ingestion and hemodynamics with respect to renal blood flow on duplex sonography, assessing the possible influence on Doppler parameters used as diagnostic criteria for renal artery stenosis. Subjects comprised 26 healthy young men (mean age: 22 ± 2 y). Sonographic measurements were made shortly after breakfast and every 1 h thereafter and were compared with values measured before the meal. Peak systolic velocity in the renal artery was elevated post-prandially, peaking at 1 h (90 ± 12 cm/s), compared with pre-prandially (73 ± 10 cm/s, p < 0.01). Similarly, acceleration time at the intra-renal segmental artery shortened to a minimum at 1 h (45 ± 5 ms) compared with baseline (51 ± 6 ms, p < 0.01). The present study indicates that renal blood flow is altered for a few hours after meal ingestion. Attention should be paid to the interpretation of data measured after meals on duplex sonography for diagnosis of renal artery stenosis.     

Knee area tissue oxygen saturation is predictive of 14-day mortality in septic shock

Purpose

Thenar eminence tissue oxygen saturation (StO₂) was developed to assess organ perfusion. However, mottling, a strong predictor of mortality in septic shock, develops preferentially around the knee. We aimed to evaluate the prognostic value of StO₂ measured around the knee in septic shock patients and compare it to thenar StO₂.

Methods

This was a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included. Parameters were recorded when vasopressors were started (H0) and every 6?h during 24?h. Their predictive value was assessed on 14-day mortality.

Results

Fifty-two patients were included. SOFA score was 11 (9–15) and SAPS II was 56 (40–72). At 6?h after ICU admission (H6), mean arterial pressure, cardiac index, and central venous pressure were not different between non-survivors and survivors; but non-survivors had higher arterial lactate level (8.8?±?5.0 vs. 2.2?±?1.5?mmol/l, P?P?2 (62?±?20 vs. 72?±?9?%, P?=?0.03). At H6, StO₂ was lower in non-survivors; this difference was not significant for thenar StO₂ (70?±?15 vs. 77?±?12?%, P?=?0.10) but was very pronounced for knee StO₂ (39?±?23 vs. 71?±?12?%, P?2 was associated with a higher mottling score (P?P?R ²?=?0.2), and a lower urinary output (P?=?0.02, R ²?=?0.12).

Conclusion

After initial septic shock resuscitation, StO₂ measured around the knee is a strong predictive factor of 14-day mortality.