Acute kidney injury following the concurrent administration of antipseudomonal ß-lactams and vancomycin: a network meta-analysis.

BACKGROUND: Acute kidney injury is a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. OBJECTIVES: This meta-analysis aims to comparatively assess the nephrotoxicity of antipseudomonal ß-lactams when combined with vancomycin. DATA SOURCES: Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. STUDY ELIGIBILITY CRITERIA: Studies evaluating acute kidney injury risk following the concurrent use of antipseudomonal ß-lactams and vancomycin were selected. PARTICIPANTS: Adult and paediatric patients treated in hospital or intensive care unit. INTERVENTIONS: Administration of vancomycin combined with any antipseudomonal ß-lactam. METHODS: Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. RESULTS: Forty-seven cohort studies were included, with a total of 56 984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates than vancomycin monotherapy (odds ratio (OR) 2.05, 95% confidence intervals (CI) 1.17-3.46) and its concurrent use with meropenem (OR 1.84, 95% CI 1.02-3.10) or cefepime (OR 1.80, 95% CI 1.13-2.77). In paediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR 4.18, 95% CI 1.01-17.29) or vancomycin plus cefepime OR 3.71, 95% CI 1.08-11.24). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. CONCLUSIONS: The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.

Serum levels of adipokines in gestational diabetes: a systematic review.

OBJECTIVE: To determine the difference of serum levels of 10 adipokines (apelin, chemerin, fatty acid-binding protein-4, fibroblast growth factor-21, monocyte chemoattractant protein-1, nesfatin-1, omentin-1, resistin, vaspin, and visfatin) among women with gestational diabetes and healthy pregnant controls. MATERIALS AND METHODS: Literature search was conducted using the 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, along with the reference list of the included studies. RESULTS: Ninety-one studies were included in the present review, with a total number of 11,074 pregnant women. A meta-analysis was not conducted due to the high inter-study heterogeneity. Current evidence suggests that fatty acid-binding protein-4 levels are significantly increased in pregnancies complicated with gestational diabetes, while no association of serum apelin and monocyte chemoattractant protein-1 with the disease can be supported. Data regarding the rest adipokines are conflicting, since the available studies did not unanimously indicate a significant change of their levels in gestational diabetes. CONCLUSIONS: The findings of the present systematic review suggest the promising role of fatty acid-binding protein-4 in the prediction of gestational diabetes, while inconsistent evidence exists regarding the rest novel adipokines. Future cohorts are needed to assess their predictive efficacy and fully elucidate their contribution in the disease.

The impact of subcutaneous tissue suturing at caesarean section on wound complications: a meta-analysis.

BACKGROUND: Caesarean wound complications are frequently observed in everyday practice. OBJECTIVES: To study whether subcutaneous tissue closure following caesarean section results in decreased wound complications. SEARCH STRATEGY: 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. SELECTION CRITERIA: Randomised and quasi-randomised trials that investigated the impact of subcutaneous tissue suturing on wound complications following caesarean section were held eligible for inclusion. Retrospective studies and prospective nonrandomised studies were excluded from the present meta-analysis. DATA COLLECTION AND ANALYSIS: The methodological quality of studies was assessed with the Jadad scale. Statistical meta-analysis was performed with the RevMan 5.3 software. MAIN RESULTS: Ten studies were finally included in our meta-analysis, which involved 3696 women delivered by caesarean section. Re-approximation of the subcutaneous tissue significantly reduced the odds of developing any type of wound complication [3811 women, random effects model (REM), odds ratio (OR) 0.66, 95% CI 0.47-0.93]. The incidence of seroma was also decreased (1979 women, REM, OR 0.53, 95% CI 0.33-0.84). On the other hand, the incidence of haematoma remained unaffected by subcutaneous closure (1663 women, REM, OR 0.74, 95% CI 0.22-2.42) as well as the likelihood of developing a wound infection (1971 women, REM, OR 0.99, 95% CI 0.70-1.41). CONCLUSIONS: The results of our meta-analysis suggest that subcutaneous tissue closure may benefit women undergoing caesarean section. Current data in women with high body mass index remain very limited; hence, definitive conclusions are precluded for this specific group. TWEETABLE ABSTRACT: Subcutaneous tissue closure may benefit women undergoing caesarean section.

The potential effect of biological sealants on colorectal anastomosis healing in experimental research involving severe diabetes.

Colorectal anastomoses continuous to pose a significant challenge in current surgical practice. Anastomotic leakage remains one of the most frequent and dramatic complications of colorectal surgery, even in centres of high specialisation. Diabetes is a well-established independent factor which results in higher anastomotic leakage rates. Fibrin sealants have been applied in experimental and clinical studies for the prevention of anastomotic dehiscence. However, little is known regarding their impact on diabetic patients. Several fibrin sealants have been proposed as adjunct to standard surgical techniques to prevent leakage from colonic anastomoses following the reversal of temporary colostomies, approved for general haemostasis. This review summarises current advances in colorectal anastomoses and provides evidence that may strengthen the need for tissue sealants in colorectal anastomoses of diabetic patients. We searched Medline (1966-2016) and Scopus (2004-2016) for current evidence in the field. To date, there is no evidence to support the use of fibrin sealants as an adjunct in diabetic patients who undergo colorectal surgery. Experimental animal models with extreme diabetes could be of significant use in the present field and further research is needed prior to application of fibrin sealants in a clinical setting.

Atherosclerosis regression study in rabbits upon olive pomace polar lipid extract administration.

BACKGROUND AND AIMS: Virgin olive oil polar lipid extract (OOPL) and olive pomace polar lipid extract (PPL) have similar antiatherosclerotic effects in cholesterol-fed rabbits. Our aim was to compare the effect of PPL with that of simvastatin on the progression of atherogenesis. METHODS AND RESULTS: Rabbits were fed an atherogenic diet for 6 weeks in order to develop dyslipidemia and atheromatous lesions. Following documentation of these events in random animals (group A, n=6), the remaining were fed for 3 weeks with: standard chow alone (group B, n=6), chow supplemented with PPL (group C, n=6), and chow supplemented with simvastatin (group D, n=6). Blood was collected at 0, 6 and 9 weeks, to determine plasma lipid levels, plasma PAF-AH activity, platelet aggregation (PAF-EC(50)), resistance of plasma to oxidation (RPO) and extent of atheromatous lesions in aortas. The atherogenic diet induced dyslipidemia and increased PAF-AH activity. Dyslipidemia and PAF-activity reduced more effectively in groups C and D. RPO decreased in group B only. PAF-EC(50) values decreased in group C only. Atherogenesis progression in group C was prevented to an extent indistinguishable from that in group D. PAF-AH activity was positively correlated, whereas RPO was negatively correlated with the extent of atheromatous lesions. CONCLUSION: PPL, as a dietary supplement, is equipotent to simvastatin in preventing the progression of atherogenesis.

The effect of lead intoxication on endocrine functions.

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Laparoscopic bowel injury: role of the site and the instrument type: study with an animal model.

BACKGROUND: Unrecognized laparoscopic bowel injuries are complications that can occur during any laparoscopic procedure. These complications have variable morbidity and mortality rates, and their early clinical signs of inflammation are not typical. Therefore, a study was planned to predict the mechanical behavior of the injured bowel, taking into consideration two parameters: the size of the instrument and the site of the injury. METHODS: For this study, 78 Wistar rats were divided into eight study groups and one control group with two subgroups. Bowel injury was created using different sizes of needles and electrocautery on two different bowel sites: the jejunum and the terminal ileum. The animals were killed 48 h after surgery, followed by harvesting of the injured part of the bowel and measurement of the intraluminal pressure at which the bowel ruptured. RESULTS: The mean jejunum and terminal ileum rupture pressures on the injured bowel were significantly lower than on the intact bowel. The mean terminal ileum rupture pressures were significantly lower than those of the jejunum. CONCLUSIONS: The terminal ileum appears to be more fragile than the jejunum regardless of the size of the instrument that caused the injury. However, wider instrument tips cause more serious consequences.

sRANKL/osteoprotegerin complex and biochemical markers in a cohort of male and female hemodialysis patients.

OBJECTIVE: The processes involved in bone remodeling are under the control of a multitude of systemic and local factors. Receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) complex seems to be one of the major modulators of bone remodeling. In chronic renal failure, the cytokine systems involved in the regulation of bone turnover may be influenced, and are therefore likely to contribute to the pathogenesis of renal bone disease. The aim of the present study was the evaluation of RANKL/OPG complex in concert with other biochemical parameters in hemodialysis (HD) patients and the investigation of possible correlations between the serum levels of its components and several clinical parameters of these patients. METHODS: We measured serum levels of intact PTH (iPTH), total serum RANKL (sRANKL), osteoprotegerin (OPG), alkaline phosphatase, osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) in 104 HD patients and in 40 healthy controls. RESULTS: The average serum OPG level was significantly higher, whereas the average serum concentration of RANKL was nonsignificantly lower in patients on HD therapy than in age-matched healthy controls. Consequently, the mean sRANKL/OPG ratio was significantly lower in patients. Among HD patients, serum level of OPG increased significantly with aging and with a longer duration of hemodialysis. RANKL levels were inversely correlated with age nonsignificantly in the whole group of patients and significantly in the female subgroup (r=-0.322, p=0.035), whereas RANKL/OPG ratio declined significantly with age in the entire cohort of patients (r=-0.259, p=0.008). In addition, iPTH, OC, TRAP were significantly higher in female, whereas RANKL/OPG ratio was significantly higher in male than female patients. CONCLUSIONS: Lower values of sRANKL/OPG ratio in HD patients, as well as the age and duration of HD dependent increase of serum OPG and the age-dependent decrease of sRANKL concentration especially in women cannot be explained by the elimination of renal clearance only. Alterations in sRANKL/OPG ratio might reflect a compensatory mechanism to modulate bone remodeling in these patients.

Dietary L-aspartate and L-glutamate inhibit fatty streak initiation in cholesterol-fed rabbit.

BACKGROUND AND AIM: Low-density lipoprotein (LDL) oxidation is a potential atherogenic agent, and protecting LDL from oxidation prevents atherogenesis. It has been shown that L-aspartate and L-glutamate decrease lipid peroxidation after reoxygenation by means of the initiation of the cardiopulmonary bypass circuit (CPB), when supplemented to the CPB prime, and so they may protect against atherogenesis. The aim of this study was to evaluate the effect of the dietary administration of L-aspartate and L-glutamate on fatty streak onset in cholesterol-fed rabbit. METHODS AND RESULTS: Male New Zealand white rabbits were fed for four weeks with either a high-cholesterol plus corn oil diet (control group) or the same diet supplemented with 12.5 mM L-aspartate and 12.5 mM L-glutamate in drinking water (Asp + Glu group). The mononuclear cells adhering to the endothelium and the intimal foam cells of the thoracic aorta were used to quantify the extent of atherosclerosis. Total serum cholesterol and lipid peroxidation activity, measured as thiobarbituric acid reactive substances (TBARS), were determined 0, 1 and 4 weeks after a 2-week adaptation period. There were no between-group differences in body weight or food intake during the intervention. Serum TBARS were significantly increased in both groups during the experimental period but without any statistical difference between groups. At the end of the dietary intervention, there was a ten-fold increase in total serum cholesterol concentration in both groups vs baseline. The numbers of adherent mononuclear cells and intimal foam cells were both significantly lower in the Asp + Glu group. CONCLUSIONS: Our results suggest that dietary supplementation with L-aspartate and L-glutamate seems to protect the arterial wall from atherogenesis in an experimental animal.