Adherence to Surgical Antibiotic Prophylaxis in the Field of Vascular Surgery.

Background: Insufficient surgical antibiotic prophylaxis (SAP) can lead to prolonged hospitalization, hospital re-admissions, increased morbidity and mortality, and higher healthcare costs. Overdoing prophylaxis can result in antimicrobial resistance, Clostridium difficile infections, and acute kidney failure. Patients and Methods: To investigate the adherence to local SAP guidelines for vascular surgery, a retrospective observational single center intervention study was performed in a Dutch hospital. Results: Antibiotic choice, dose, interval, timing, and duration were adherent to the guidelines in 96%, 97%, 96%, 85%, and 41% of the surgeries, respectively. Adherence to all five aspects was achieved in only 37% of all procedures. Conclusions: Further interventions are necessary to improve specific parameters such as duration and timing.

Recovery of circadian melatonin rhythm after a melatonin holiday in daytime haemodialysis patients on long-term exogenous melatonin.

The effects of exogenous melatonin on sleep diminish after its long-term use in haemodialysis patients. Our aim was to determine whether melatonin levels accumulate after chronic (at least three months) use of exogenous melatonin, 5 mg daily, and whether discontinuation of this treatment improves endogenous melatonin production and improves the circadian sleep-wake rhythm. In this case series, stable haemodialysis patients discontinued their chronic exogenous melatonin usage for seven days and melatonin concentrations in saliva were analysed. The primary endpoint was recovery of a normal circadian melatonin rhythm. Secondary endpoints were the effects on melatonin pharmacokinetics and sleep parameters. At day three after discontinuation the normal circadian melatonin rhythm recovered in the two patients who discontinued the treatment for the full week. They also had an effective maximum trough level of melatonin. Discontinuing melatonin seems to result in recovery of the circadian rhythm, based on achievement of effective melatonin thresholds. Further research is necessary to investigate whether sleep parameters improve after a drug holiday.most appropriate treatment.

Melatonin and renal protection: novel perspectives from animal experiments and human studies (review).

Chronic kidney disease (CKD) is a serious public health problem. Current therapies are designed to slow down progression of the disease and avoid the necessity of dialysis or kidney transplantation. CKD is characterized by chronic inflammation and progressive cell death resulting in fibrotic rebuilding of renal tissue. Melatonin, the primary product of the pineal gland, has been shown to have pluripotent protective effects in many organs and tissues. It exerts anti-hypertensive, anti-inflammatory, anti-apoptotic, and antiremodelling actions. A principal mechanism of these numerous melatonin benefits resides in its extraordinary high efficacy as an antioxidant and scavenger protecting cells both extracellularly and in all subcellular structures. In addition to these receptor-independent actions, the effects of melatonin via specific MT-receptors may be beneficial. In several animal models of CKD, involving experimental hypertension, diabetes mellitus and various models of nephrotoxicity, melatonin reduced the oxidative burden, attenuated the chronic inflammation and limited apoptosis. These effects were associated with the reduction of proteinuria, damage of parenchymal cells and fibrosis. In humans, melatonin's chronobiological action attenuates sleep disturbances in hemodialyzed patients suffering from a relative melatonin deficiency. Moreover, melatonin reduces the oxidative burden and improves iron metabolism in hemodialyzed patients. In conclusion, the pleiotropic physiological actions of melatonin induce beneficial effects at numerous pathophysiological levels related to CKD both under experimental and clinical conditions. It is hoped that this review will prompt a large clinical trial to determine the efficacy of this nontoxic indoleamine as a potential treatment for this debilitating disease.

The role of melatonin treatment in chronic kidney disease.

The pineal hormone melatonin plays a major role in circadian sleep-wake rhythm. Patients with Chronic Kidney Disease (CKD), especially those who are on hemodialysis, frequently suffer from sleep disturbances. In this review an overview is given of the classification of stages of chronic kidney disease, followed by a presentation of the circadian rhythm disorders in renal disease involving sleep disturbances in relation to melatonin deficiency. The therapeutic benefit of melatonin treatment in sleep disorders related to chronic kidney disease including the controlled trials solving this topic, is described. Furthermore, the beneficial effect of melatonin on blood pressure alterations in CKD states and the protection of melatonin in oxidative stress and inflammation in renal disorders are explored. Finally a hypothetic model is described for the relation between circadian rhythm disorders and CKD.

The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.

OBJECTIVE: Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function. METHODS: The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations. RESULTS: Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found. CONCLUSION: The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.

Improving melatonin circadian phase estimates.

The quality and quantity of sleep is to a large extent determined by whether the sleep period is in alignment with the most favorable circadian time window for sleep. Misalignment results in compromised sleep. In order to determine this circadian time window, the 24-h profile of melatonin secretion is generally considered to provide the most optimal estimate. Melatonin secretion occurs only during the night, and several methods to determine its onset and offset markers have been proposed. In spite of the usefulness of determining circadian phase estimates from melatonin, its feasibility is somewhat restricted because the required number of repeated measurements comes at a high cost for compliance and laboratory assays. In addition, the complexity of some of the previously proposed methods to analyze data and obtain phase estimates may require a statistician. We here propose a set of novel functions to better describe the typical melatonin profile, which usually has a rather fixed baseline level during the day, has differences in the steepness of its rising and falling limbs, and may have a nocturnal plateau or even two peaks instead of one during the night. The functions can easily be fitted, even to incomplete or noisy melatonin data, with the most common statistical software packages, and the resulting parameters give direct information on the mentioned characteristics, which provide important additions to complete the usual restricted information on phase and amplitude. We show that the proposed curves fit better than single- to three-harmonic cosine curves to the typical melatonin profiles of both healthy subjects (n=13) and subjects diagnosed with Delayed Sleep Phase Syndrome (DSPS, n=27), Disorders of Initiating and Maintaining Sleep (DIMS, n=9), or sleep complaints not otherwise specified (n=7). Of note, because the functions provide a parsimonious description of the melatonin profile, phase estimates derived from them are more reliable (i.e., robust for noise and data loss). We illustrate that phase estimates deviate on average only by about 10 min in case of the loss of some of the data points and in case of the addition of noise. Finally, we introduce a sparse-sampling schedule tailored to capture the most important aspects of the melatonin curve. It is shown that such schedule - reducing the number of samples by more than 50% - in combination with the proposed functions results in reliable melatonin onset phase estimates, deviating only about 10 min from estimates based on 24 samples. The proposed methods strongly contribute to the feasibility, in terms of both cost and analysis availability, for researchers and clinicians to include the most reliable marker of the circadian timing system in their diagnosis and treatment evaluations.