In vivo evaluation of the effects of moisturisers on transepidermal water loss using factorial designs

The effect of topical applications of pyrrolidone carboxylic acid (PCA), sodium lactate (NaL) and urea on in vivo transepidermal water loss (TEWL) in healthy volunteers was studied. The moisturizing compounds were applied both singly and as mixtures using a 2² factorial design. It is shown that all three compounds increased TEWL and that moreover, urea and PCA exerted synergism. No such interaction was observed between urea and sodium lactate. The study provides a rational basis for the co-formulation of urea and PCA in moisturising products for topical use.     

Reduction in endotoxin-induced organ dysfunction and cytokine secretion by a cyclic nitrone antioxidant

Multiple organ dysfunction (MOD) is the leading cause of mortality in septic patients with circulatory shock. Recent evidence suggests that the overproduction of the cytokine, tumor necrosis factor-α (TNF), and oxygen free radical molecules may mediate the progression of sepsis to MOD and death. In this study, we have examined the ability of MDL 101,002, a free radical scavenger, to reduce organ dysfunction and cytokine secretion induced by lipopolysaccharide (LPS) administration in rats. Treatment with MDL 101,002 (10–60 mg/kg, i.p.) 30 min prior to an LPS challenge resulted in a dose-dependent reduction in several markers indicative of organ dysfunction and mortality. MDL 101,002 markedly decreased LPS-induced liver and kidney damage as indicated by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) or urea and creatinine, respectively. MDL 101,002 also prevented LPS-induced pulmonary edema, but did not prevent leukopenia and only partially reduced thrombocytopenia. Associated with these improvements in organ dysfunction and survival was a modest decrease in LPS-stimulated interleukin-1α (IL-1α) and interleukin-1β (IL-1β) secretion and a marked (>90%) inhibition of TNF secretion by MDL 101,002. The data are consistent with a role for oxygen free radicals in the development of endotoxin-induced organ dysfunction and shock and suggest that free radical scavengers could reduce the mortality consequent to sepsis by decreasing organ dysfunction, at least in part, through a reduction in free radical stimulated cytokine secretion.     

Early hypothermia as risk factor in severely burned patients: A retrospective outcome study

IntroductionBurn trauma-related hypothermia is a frequent observation but risk factors and impact on patient related outcome are ambiguously reported. It is expected that hypothermia is associated with increased mortality and reduced overall outcome in severely burned patients, but available evidence is limited.MethodsThis retrospective single-center-study reviewed preclinical service protocols and medical records of patients sustaining a burn with a total body surface area (TBSA) ≥15% from 2008 to 2012. General patient and burn specific characteristics, outcome parameters as well as body temperature at admission measured via urine catheter or nasal temperature probe were recorded and statistically analyzed comparing normothermic (≥36 °C), mild hypothermic (<36 °C) and severely hypothermic (<34.5 °C) patients. Chi-square test was performed to demonstrate impact of hypothermia on primary outcome parameters and to reveal risk factors for developing hypothermia. To assess independent influences on mortality, a multivariate logistic regression analysis was performed.ResultsOut of 300 patients matching inclusion criteria, a sufficient record of temperature was found in 144 patients (48%). Out of 141 eligible patients with an average burn extent (SD) of 33.38% (24.5%) TBSA, 31.9% (n = 45) suffered from severe hypothermia (<34.5 °C) and 28.4% (n = 40) showed mild hypothermia. Total burn extent, presence of full thickness burns, presence of inhalation injury, preclinical mechanical ventilation and administration of sedative drugs were risk factors for developing hypothermia. Patients’ age, total burn extent and presence of full thickness burns could be identified as independent factor for mortality. Although a trend towards an independent positive influence of normothermia at admission on mortality was seen, it was not statistically significant.ConclusionIncidental hypothermia of burned patients is associated with an increased mortality and needs to be addressed by emergency health care providers and immediately at the burn center. Especially patients with extensive burns, full-thickness burns, inhalation injury or patients undergoing preclinical intubation are at risk for hypothermia and benefit from any measures for temperature preserving.     

High on-clopidogrel platelet reactivity and chronic kidney disease: a meta-analysis of literature studies

Background. The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD). Methods. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Results. Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23–1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p?p?=?0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p?=?0.004). Conclusions. Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.     

Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

Aims/hypothesis

Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes.

Methods

Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 307 controls).

Results

Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA_1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude.

Conclusions/interpretation

Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications.

     

Salvage irrigation-suction in gracilis muscle repair of complex rectovaginal and rectourethral fistulas

AIM:To evaluate the efficacy of gracilis muscle transposition and postoperative salvage irrigation-suction in the treatment of complex rectovaginal fistulas(RVFs)and rectourethral fistulas(RUFs).METHODS:Between May 2009 and March 2012,11female patients with complex RVFs and 8 male patients with RUFs were prospectively enrolled.Gracilis muscle transposition was undertaken in all patients and postoperative wound irrigation-suction was performed in patients with early leakage.Efficacy was assessed in terms of the success rate and surgical complications.SF-36 quality of life(QOL)scores and Wexner fecal incontinence scores were compared before and after surgery.RESULTS:The fistulas healed in 14 patients after gracilis muscle transposition;the initial healing rate was73.7%.Postoperative leakage occurred and continuous irrigation-suction of wounds was undertaken in 5patients:4 healed and 1 failed,and postoperative fecal diversions were performed for the patient whose treatment failed.At a median follow-up of 17 mo,the overall healing rate was 94.7%.Postoperative complications occurred in 4 cases.Significant improvement was observed in the quality outcomes framework scores(P<0.001)and Wexner fecal incontinence scores(P=0.002)after the successful healing of complex RVFs or RUFs.There was no significant difference in SF-36 QOL scores between the initial healing group and irrigationsuction-assisted healing group.CONCLUSION:Gracilis muscle transposition and postoperative salvage wound irrigation-suction gained a high success rate in the treatment of complex RVFs and RUFs.QOL and fecal incontinence were significantly improved after the successful healing of RVFs and RUFs.