Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence

Pituitary adenylate cyclase-activating polypeptide ameliorates vascular dysfunction induced by hyperglycaemia

BACKGROUND: Short-lasting hyperglycaemia occurs frequently in prediabetes and poorly controlled diabetes mellitus leading to vascular damage. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play a protective role in vascular complications of diabetes; moreover, antioxidant effects of PACAP were also described. Therefore, we hypothesized that PACAP exerts protective effects in short-term hyperglycaemia-induced vascular dysfunctions. METHODS: After short-term hyperglycaemia, acetylcholine-induced and sodium nitroprusside-induced vascular relaxation of mouse carotid arteries were tested with a myograph with or without the presence of PACAP or superoxide dismutase. Potential direct antioxidant superoxide-scavenging action of pituitary adenylate cyclase-activating peptide was tested with pyrogallol autoxidation assay; furthermore, the effect of pituitary adenylate cyclase-activating peptide or superoxide dismutase was investigated on hyperglycaemia-associated vascular markers. RESULTS: PACAP administration resulted in reduced endothelial dysfunction after a 1-h hyperglycaemic episode. PACAP was able to restore acetylcholine-induced relaxation of the vessels and improved sodium nitroprusside-induced relaxation. This effect was comparable to the protective effect of superoxide dismutase, but PACAP was unable to directly scavenge superoxide produced by autoxidation of pyrogallol. Endothelial dysfunction was associated with elevated levels of fibroblast growth factor basic, matrix metalloproteinase 9 and nephroblastoma overexpressed gene proteins. Their release was reduced by PACAP administration. CONCLUSION: These results suggest a strong protective role of PACAP in the vascular complications of diabetes

VPAC1 receptors play a dominant role in PACAP-induced vasorelaxation in female mice

PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals.We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot.In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries.In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found

Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis

AIM: To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations. METHODS: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31(st), 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1). RESULTS: All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes. CONCLUSION: Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted

Theory of mind disturbances in borderline personality disorder

Impairments of theory of mind (ToM) are widely accepted underlying factors of disturbed relatedness in borderline personality disorder (BPD). The aim of this meta-analysis a was to assess the weighted mean effect sizes of ToM performances in BPD compared to healthy controls (HC), and to investigate the effect of demographic variables and comorbidities on the variability of effect sizes across the studies. Seventeen studies involving 585 BPD patients and 501 HC were selected after literature search. Effect sizes for overall ToM, mental state decoding and reasoning, cognitive and affective ToM, and for task types were calculated. BPD patients significantly underperformed HC in overall ToM, mental state reasoning, and cognitive ToM, but had no deficits in mental state decoding. Affective ToM performance was largely task dependent in BPD. Comorbid anxiety disorders had a positive moderating effect on overall and affective ToM in BPD. Our results support the notion that BPD patients' have specific ToM impairments. Further research is necessary to evaluate the role of confounding factors, especially those of clinical comorbidities, neurocognitive functions, and adverse childhood life events. Complex ToM tasks with high contextual demands seem to be the most appropriate tests to assess ToM in patients with BPD

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency

Therapeutic whole-body hypothermia reduces mortality in severe traumatic brain injury if the cooling index is sufficiently high: meta-analyses of the effect of single cooling parameters and their integrated measure

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the mortality of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure inter-study homogeneity. We extracted data on TBI severity, body temperature, mortality, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but inter-study heterogeneity was high. On the contrary, by meta-analysis of RCTs which were homogenous with regards to statistical, clinical designs and precisely reported the cooling protocol, we showed decreased odds ratio for mortality in therapeutic hypothermia compared to no cooling. As independent factors, milder and longer cooling, and rewarming at < 0.25 degrees C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical inter-study heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index

Fever is associated with reduced, hypothermia with increased mortality in septic patients: a meta-analysis of clinical trials

BACKGROUND: Sepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials. METHODS: We searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently. RESULTS: Forty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2-25.5) mortality rate in septic patients with fever (Tb > 38.0 degrees C), which was higher, 31.2% (CI, 25.7-37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9-55.7), in hypothermic patients (Tb 75%)

Is Heller myotomy better than balloon dilation? A meta-analysis

BACKGROUND AND AIM: Endoscopic balloon dilation (EBD) and laparoscopic Heller myotomy (LHM) are the most commonly performed treatment options for achalasia. Decision between these treatment options is difficult. The aim of this meta-analysis was to evaluate the efficacy of EBD compared to LHM. METHODS: The electronic databases PubMed, Embase and Cochrane Controlled Trials Registry were systematically searched for the period between January 1, 1976 and December 31, 2015. Meta-analysis was performed using the PICOS (problem, intervention, comparison, outcome, study design) format. Efficacy and safety of EBD were compared to LHM. Forest plot analyses were used to illustrate the success rate, perforation rate and post-procedural gastroesophageal reflux. RESULTS: Using the search strategy, eight studies met the selection criteria and were included in the meta-analysis. The total number of patients included was 749 (360 in the EBD group and 389 in the LHM group). The success rate was lower in the EBD group than in the LHM group (OR=0.486; CI: 0.304-0.779; p=0.003). The rate of perforation did not differ significantly between the EBD and LHM group (RR= 0.635, CI: 0.340-1.186, p=0.154). The incidence of post-procedural symptomatic gastroesophageal reflux did not differ between the two treatment groups (RR=0.663, CI: 0.328-1.343, p=0.254). CONCLUSION: Our data suggest that the efficacy of LHM is superior to that of EBD, while there is no difference in safety between the two treatment groups

Steroid but not biological therapy elevates the risk of venous thromboembolic events in inflammatory bowel disease: a meta-analysis

Background and aim: Inflammatory bowel disease [IBD] is associated with 1.5- to 3-fold increased risk of venous thromboembolic events [VTE]. The aim of this study was to determine the risk of VTE in IBD as a complication of systemic corticosteroids and anti-tumor necrosis factor alpha [TNFalpha] therapies. Methods: A systematic review and meta-analysis was conducted, which conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] statement. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for English-language studies published from inception inclusive 15 April 2017. The population-intervention-comparison-outcome [PICO] format and statistically the random-effects and fixed-effect models were used to compare VTE risk during steroid and anti-TNFalpha treatment. Quality of the included studies was assessed using the Newcastle-Ottawa scale. PROSPERO registration number is 42017070084. Results: We identified 817 records, of which eight observational studies, involving 58,518 IBD patients, were eligible for quantitative synthesis. In total, 3,260 thromboembolic events occurred. Systemic corticosteroids were associated with a significantly higher rate of VTE complication in IBD patients as compared to IBD patients without steroid medication [OR: 2.202; 95% CI: 1.698-2.856, p < 0.001]. In contrast, treatment with anti-TNFalpha agents resulted in a 5-fold decreased risk of VTE compared to steroid medication [OR: 0.267; 95% CI: 0.106-0.674, p = 0.005]. Conclusion: VTE risk should be carefully assessed and considered when deciding between anti-TNFalpha and steroids in the management of severe flare-ups. Thromboprophylaxis guidelines should be followed, no matter the therapy choice