Evaluation of Serum Interleukin-17 (IL-17) Levels as a Diagnostic Marker in Pancreatic Adenocarcinoma

Abstract

Background

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression. The role of interleukin (IL-17) in cancer is currently under debate. This study was conducted to investigate the serum levels of IL-17 in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters.

Material and Methods

Thirty-five patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum IL-17 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 35 healthy controls were included in the analysis.

Results

The median age at diagnosis was 61 years, range 38–84 years; 21 (60 %) patients were men. The tumor was located in the head of pancreas in 24 (69 %) patients. The most common metastatic site was liver in 20 patients with metastasis (n = 18, 90 %). The median follow-up time was 24.0 weeks (range 1.0–191.0 weeks). At the end of the observation period, 12 (34 %) patients experienced disease progression and 23 patients (66 %) were dead. Forty-four percent of 18 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. Median progression-free survival and overall survival of the whole group were 13.7 ± 2.3 weeks [95 % confidence interval (CI) = 9–18 weeks] and 48.0 ± 12.8 weeks (95 % CI = 23–73 weeks), respectively. The baseline serum IL-17 levels were significantly higher in patients with PA than in the control group (p = 0.001). Moreover, serum IL-17 levels were significantly higher in the patients with large pathologic tumor status and low albumin levels (p = 0.04 and p = 0.03, respectively). However, serum IL-17 assays had no prognostic roles on outcome.

Conclusion

Although serum levels of IL-17 assays were found to be diagnostic value, no predictive and prognostic value was determined in PA patients.

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GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice

Publication date: 15 February 2016
Source:Behavioural Brain Research, Volume 299
Author(s): Lakshmi Rajagopal, Jeffrey S. Burgdorf, Joseph R. Moskal, Herbert Y. Meltzer
GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-d-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30mg/kg.i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0mg/kg, but not 0.3mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications.



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Abdel El Manira elected in the Royal Swedish Academy of Sciences

KI Professor Abdel El Manira has been elected member of The Royal Swedish Academy of Sciences in the Academy's Class for biosciences. Abdel El Manira is a professor at the Department of Neuroscience at Karolinska Institutet since 2005. At the Academy's general meeting on 11 November El Manira was one of three new elected members. Read more on the KVA website.

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Social Media and Scientific Meetings:

Publication date: Available online 4 December 2015
Source:Academic Radiology
Author(s): Paul M. Bunch, Jeremy R. Wortman, Katherine P. Andriole
Rationale and ObjectivesViewers of electronic education exhibits at the 2013 and 2014 Radiological Society of North America meetings had the opportunity to "like" exhibits, as one might "like" a Facebook or an Instagram post. The purposes of this study were (1) to evaluate for a relationship between exhibit popularity and receiving an award or RadioGraphics invitation, (2) to evaluate for a relationship between exhibit recognition and subsequent popularity, and (3) to quantify and compare the electronic education exhibit likes at the 2013 and the 2014 meetings.Materials and MethodsExhibit likes were recorded at the midpoints and ends of both meetings. Data analyses were performed by means of one-way analysis of variance and chi-square tests.ResultsThere were similar numbers of electronic education exhibits at the 2013 (1856) and 2014 (1793) meetings with no significant difference between meeting years in the number of exhibits chosen for awards (423 vs. 404, P = 0.88) or for RadioGraphics solicitation (190 vs. 169, P = 0.46). In both meeting years, there were statistically significant associations between initial and overall exhibit popularity and exhibit recognition, as well as between exhibit recognition and subsequent popularity. A 152% increase in total likes recorded was observed at the 2014 meeting as compared to the 2013 meeting (11074 vs. 4391, P < 0.0001).ConclusionsPopular exhibits were significantly more likely to receive awards and RadioGraphics invitations. Receiving an award or RadioGraphics invitation was associated with subsequent increased exhibit popularity. Significantly more likes were recorded at the 2014 Radiological Society of North America meeting than at the 2013 meeting.



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PLCζ disruption with complete fertilization failure in normozoospermia

Purpose: Intracytoplasmic sperm injection (ICSI) is widely used to achieve fertilization in the presence of severe male factor, resulting in high fertilization rates. Nevertheless, 1–3 % of couples experience complete fertilization failure after ICSI.When a male factor is identified, assisted oocyte activation (AOA) can help overcome fertilization failures. The objective of this study is to describe a case of repeated complete fertilization failures after ICSI with donor oocytes, and to investigate the molecular and functional aspects of phospholipase C zeta (PLCζ) protein in the patient semen. Methods: The patient was a normozoospermic male who had previously fathered, through natural conception, four children by a different partner. Molecular and functional analysis of sperm-specific PLCζ in the patient and control samples by means of gene sequencing, immunocytochemistry, Western blot, mouse oocyte activation test (MOAT), and mouse oocyte calcium analysis (MOCA) were used. Results: PLCζ expression levels and distribution were significantly disrupted, although MOAT and MOCA did not indicate a decrease in activation ability. Conclusions: Normozoospermic males can have disrupted expression and distribution of PLCζ, and reduced activation ability after ICSI in human oocytes, despite their normal activation potential in functional testing using mouse oocytes. Discrepancy among molecular and functional data might exist, as mutations in the gene sequence may not be the only cause of alteration in PLCζ protein related to activation failures.

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Between compliance and resistance: exploring discourses on family planning in Community Health Committees in Mozambique

Objectives: Although the Mozambican government has implemented a community-based approach to family planning (FP), little is known about the appropriateness of this process. We explore how members of Community Health Committees (CHCs) address and act regarding FP. Methods/settings: An in-depth qualitative study of CHCs was conducted at two sites in Maputo province -Ndlavela and Boane-using focus group discussions (n=6), informal conversations (n=4) and observation. The analysis followed a phenomenological approach. Results: CHCs in Ndlavela appeared to transfer more of the expected information than those in Boane. However, in the CHCs at both study sites, we found heterogeneity in CHCs' perspectives leading to conflicting views among committee members (CMs). Arising issues included contraceptive type, target groups, the desirable number of children per family as well as the way FP was to be represented. Moreover, weak communication between CMs and health workers, and lack of payment for CMs' activities influenced promotion of FP. Conclusions: The two CHCs framed FP in different ways leading to inconsistent participation of CHC members in promoting FP. Policymakers should consider the diversity of discourses and aspirations of these committees when delivering information to them.

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Induction for intrahepatic cholestasis of pregnancy: why we'll never know

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Nutrition-dependent phenotypes affect sexual selection in a ladybird

Environmental factors play a crucial role in influencing sexual selection in insects and the evolution of their mating systems. Although it has been reported that sexual selection in insects may change in response to varying environments, the reason for these changes remains poorly understood. Here, we focus on the mate selection process of a ladybird, Cryptolaemus montrouzieri, when experiencing low-and high-nutrition diet regimes both in its larval and adult stages. We found that female ladybirds preferred to mate with males reared under high-nutrition diet regimes, regardless of the nutritional conditions they experienced during their own larval stages, indicating that mate choice of female C. montrouzieri is non-random and phenotype-dependent. Such mate choice may depend on visual cues (body or genitalia size) and/or chemical cues (pheromones). Further, females from high-nutrition larval diet regimes produced more eggs than those from low-nutrition larval diet regimes. In addition, diet regimes during adulthood also exerted strong effects on egg production. In summary, our study provides new insight into the mate choice of C. montrouzieri as affected by seasonal changes in resources, and suggests that food availability may be a driving force in mate choice.

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Prey consumption by phytoseiid spider mite predators as affected by diurnal temperature variations

The consumption rate of an ectothermic predator is highly temperature-dependent and is a key driver of pest-predator population interactions. Not only average daily temperature, but also diurnal temperature variations may affect prey consumption and life history traits of ectotherms. In the present study, we evaluated the impact of temperature alternations on body size, predation capacity and oviposition rate of the predatory mites Phytoseiulus persimilis Athias-Henriot and Neoseiulus californicus McGregor (Acari: Phytoseiidae) when presented with eggs of their natural prey, the two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae). For both predators, mean daily temperature as well as temperature alternation had a substantial impact on the number of prey consumed. At lower average temperatures, more eggs were killed under an alternating temperature regime (20 A degrees C/5 A degrees C and 25 A degrees C/10 A degrees C) than at the corresponding mean constant temperatures (15 and 20 A degrees C). At higher average temperatures (> 25 A degrees C), however, the opposite was observed with higher numbers of prey killed at constant temperatures than at alternating temperatures. At 25 A degrees C, temperature variation had no effect on the predation capacity. A similar trend as for the predation rates was observed for the oviposition rates of the phytoseiids. Body size of N. californicus was affected both by average daily temperature and temperature variation, with smaller adult females emerging at alternating temperatures than at constant temperatures, whereas for P. persimilis, temperature variation had no impact on its body size. Our results demonstrate that temperature variations are likely to affect biological control of T. urticae by the studied phytoseiid predators.

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Application of small molecules favoring naive pluripotency during human embryonic stem cell derivation

In mice, inhibition of both the fibroblast growth factor (FGF) mitogen-activated protein kinase kinase/extracellular-signal regulated kinase (MEK/Erk) and the Wnt signaling inhibitor glycogen synthase-3 (GSK3) enables the derivation of mouse embryonic stem cells (mESCs) from nonpermissive strains in the presence of leukemia inhibitory factor (LIF). Whereas mESCs are in an uncommitted naive state, human embryonic stem cells (hESCs) represent a more advanced state, denoted as primed pluripotency. This burdens hESCs with a series of characteristics, which, in contrast to naive ESCs, makes them not ideal for key applications such as cell-based clinical therapies and human disease modeling. In this study, different small molecule combinations were applied during human ESC derivation. Hereby, we aimed to sustain the naive pluripotent state, by interfering with various key signaling pathways. First, we tested several combinations on existing, 2i (PD0325901 and CHIR99021)-derived mESCs. All combinations were shown to be equally adequate to sustain the expression of naive pluripotency markers. Second, these conditions were tested during hESC derivation. Overall, the best results were observed in the presence of medium supplemented with 2i, LIF, and the noncanonical Wnt signaling agonist Wnt5A, alone and combined with epinephrine. In these conditions, outgrowths repeatedly showed an ESC progenitor-like morphology, starting from day 3. Culturing these "progenitor cells" did not result in stable, naive hESC lines in the current conditions. Although Wnt5A could not promote naive hESC derivation, we found that it was sustaining the conversion of established hESCs toward a more naive state. Future work should aim to distinct the effects of the various culture formulations, including our Wnt5A-supplemented medium, reported to promote stable naive pluripotency in hESCs.

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Genetic differentiation in native and introduced populations of Cryptolaemus montrouzieri (Coleoptera: Coccinellidae) and its implications for biological control programs

Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae) is an effective biological control agent of Australian origin, which has been introduced worldwide to control mealybugs. Although successfully used for > 100 yr, its introduction in a new area may cause environmental risks should the populations become invasive. In the present study, a population genetics method was used to make predictions of the invasive potential of C. montrouzieri. Our results showed a similar level of genetic diversity among all populations. No significant genetic differentiation between native and introduced populations was observed, while three populations from the native region were significantly divergent. The fact that genetic diversity was not reduced in introduced areas suggests that no bottleneck effect has occurred during introduction. To avoid rapid evolution of the introduced C. montrouzieri, the introduction records of each population should be clearly traced and introductions from multiple sources into the same area should be avoided.

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Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution

The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.

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Nanocomposite versus Mesocomposite for Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Injectable inorganic/organic composite systems consisting of well-defined mesocrystals (4–8 μm) of calcium phosphate and polypeptide thermogel significantly enhance the osteogenic differentiation of the tonsil derived mesenchymal stem cells (TMSCs). Compared to composite systems incorporating nanoparticles (10–100 nm) or pure hydrogel systems, osteogenic biomarkers including alkaline phosphatase (ALP), bone morphogenetic protein 2, and osteocalcin are highly expressed at both the mRNA level and the protein level in the mesocrystal composite systems. ALP activity of differentiated cells is also significantly higher in the mesocomposite systems compared to the nanocomposite systems or the pure hydrogel systems. The mesocomposite systems provide not only hard surfaces for binding the cells/proteins by the inorganic mesocrystals but also a soft matrix for holding the cells by the hydrogel. Through the current research, (1) a novel method of preparing mesocrystals is developed, (2) TMSCs are proved as a new resource of stem cells, and (3) the mesocomposite systems are proved to be a promising tool in controlling stem cell differentiation. (4) Finally, the research emphasizes the significance of mesoscience as a new perspective of science in controlling cell and material interfaces.

Calcium phosphate mesocrystals and polypeptide thermogel composite systems provide an effective 3D scaffold for osteogenic differentiation of incorporated stem cells. The mesocrystals provide appropriate surfaces not only for binding of proteins but also for adhesion of cells, emphasizing the significance of mesoscience covering 100 nm–10 μm in the interactions between materials and cells.

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Paediatric anaesthesia emergency data manual

No abstract available

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Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A randomised experimental study

BACKGROUND: Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. OBJECTIVES: The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. DESIGN: A randomised, experimental study. SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg−1) with or without ketamine (10 mg kg−1), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. RESULTS: Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P  0.05). CONCLUSION: Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.

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The kalaemic and neuromuscular effects of succinylcholine in centronuclear myopathy: A pilot investigation in a canine model

BACKGROUND: Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine. OBJECTIVES: We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM. DESIGN: A prospective, experimental study. SETTING: Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA. PATIENTS: Six dogs with autosomal-recessive CNM and six control dogs. INTERVENTIONS: Dogs received succinylcholine 0.3 mg kg−1 during isoflurane anaesthesia. MAIN OUTCOME MEASURES: Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation. RESULTS: All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l−1 and control 0.7 (0.4) mmol l−1 (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P 

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Persistent posthysterectomy pain: A prospective, observational study

BACKGROUND: There is a large variation in the prevalence of persistent postsurgical pain depending on the type of surgery. It is unclear how common persistent postsurgical pain is after vaginal or laparoscopic hysterectomy. OBJECTIVES: The objective of this study was to define the prevalence of persistent postsurgical pain 6 months after laparoscopic or vaginal hysterectomy for benign causes and to ascertain the intensity of the pain and its possible predictors. DESING: A prospective, observational study. SETTING: Pirkanmaa Hospital District between October 2008 and September 2013. PATIENTS: Two hundred and forty-two women who underwent laparoscopic (150) or vaginal (92) hysterectomy for benign causes and who also participated in our earlier studies concerning acute pain. INTERVENTIONS: A pain questionnaire and a prestamped return envelope were mailed to all women 6 months after surgery. If the questionnaire had not been returned within 4 weeks, a reminder was sent. Data regarding preoperative pain and acute postoperative pain were collected from the records of our earlier studies concerning acute pain. The patient characteristics and surgical outcomes were collected from the patients' medical records. MAIN OUTCOME MEASURE: The prevalence of persistent postsurgical pain 6 months after hysterectomy. RESULTS: The response rate was 94% (227 respondents). Twenty-seven (18.9%) of 143 patients who had no pain preoperatively had persistent pain after surgery. Overall, 26.0% of patients had persistent pelvic pain 6 months after surgery. On an 11-point numeric rating scale (NRS), most of the patients rated their average pain as mild (NRS 0 to 3) and only 6.9% rated their worst pain as severe (NRS 7 to 10). Smoking, acute postoperative pain at 4 h after surgery and a laparoscopic approach were significantly associated with persistent pain in a multivariable analysis. CONCLUSION: Persistent posthysterectomy pain is common, but pain is mild and does not interfere with daily activities for most of the patients 6 months after surgery. Smoking is the strongest predictor for persistent pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01537731.

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Response to rocuronium and its determinants in patients with myasthenia gravis: A case–control study

BACKGROUND: Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. OBJECTIVES: To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. DESIGN: Case control study. SETTING: Kumamoto University Hospital, November 2010 to September 2013. PATIENTS: Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95

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Failure of sugammadex to reverse rocuronium-induced neuromuscular blockade: Simply an outlier or are we missing something?

No abstract available

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Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial

BACKGROUND: Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. OBJECTIVE: The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. DESIGN: A prospective clinical trial. SETTING: Two university hospitals, from 1 October 2011 to 31 January 2012. PATIENTS: Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) 90 ml min−1). INTERVENTION: Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg−1 was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. MAIN OUTCOME MEASURES: The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. RESULTS: After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. CONCLUSION: In patients with renal failure, sugammadex (4 mg kg−1) effectively and safely reversed profound rocuronium induced neuromuscular block, but the recovery was slower than healthy patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01785758.

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Can residual paralysis be avoided?: A critical appraisal of the use of sugammadex

No abstract available

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Predictors of the variability in neuromuscular block duration following succinylcholine: A prospective, observational study

BACKGROUND: The duration of neuromuscular block (NMB) following succinylcholine administration is characterised by a high interindividual variability. However, this has not yet been quantified in a large sample of surgical patients. The significance of underlying clinical factors is unknown. OBJECTIVE: The objective of this study was to profile the variability in NMB duration following a standard dose of succinylcholine and to investigate contributing clinical and genetic factors. DESIGN: A prospective, observational study. SETTING: Tertiary referral centre. PATIENTS: In a total of 1630 surgical patients undergoing a rapid sequence induction and intubation, clinical risk factors for a prolongation in NMB duration following succinylcholine were assessed. In a subset of 202 patients, additional biochemical and molecular genetic investigations of butyrylcholinesterase were performed. INTERVENTION: A standard 1 mg kg−1 dose of succinylcholine after administration of an induction drug and an opioid. MAIN OUTCOME: NMB duration measured as the time between administration of succinylcholine until reappearance of palpable muscular response to supramaximal transcutaneous ulnar nerve stimulation. RESULTS: NMB varied from 80 s to 44 min with a median duration of 7.3 min. Sixteen percent of patients had NMB duration in excess of 10 min. A multivariable survival model identified physical status, sex, age, hepatic disease, pregnancy, history of cancer and use of etomidate or metoclopramide as independent risk factors for a prolonged NMB. Three novel butyrylcholinesterase variants were identified: p.Ile5Thr; p.Val178Ile; and p.Try231Ser. CONCLUSION: Neuromuscular blockade duration in excess of 10 min occurred in 16% of a general surgical population following a single dose of succinylcholine. The multivariable model of clinical risk factors for prolonged NMB revealed a negative predictive value of 87%, thereby indicating that absence of such risk factors may reliably predict a shorter duration of NMB. In patients with clinical risk factors for a prolonged NMB or with butyrylcholinesterase mutations, an alternative to succinylcholine should be considered.

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Chronic postsurgical pain in Europe: An observational study

BACKGROUND: Chronic postsurgical pain (CPSP) is an important clinical problem. Prospective studies of the incidence, characteristics and risk factors of CPSP are needed. OBJECTIVES: The objective of this study is to evaluate the incidence and risk factors of CPSP. DESIGN: A multicentre, prospective, observational trial. SETTING: Twenty-one hospitals in 11 European countries. PATIENTS: Three thousand one hundred and twenty patients undergoing surgery and enrolled in the European registry PAIN OUT. MAIN OUTCOME MEASURES: Pain-related outcome was evaluated on the first postoperative day (D1) using a standardised pain outcome questionnaire. Review at 6 and 12 months via e-mail or telephonic interview used the Brief Pain Inventory (BPI) and the DN4 (Douleur Neuropathique four questions). Primary endpoint was the incidence of moderate to severe CPSP (numeric rating scale, NRS ≥3/10) at 12 months. RESULTS: For 1044 and 889 patients, complete data were available at 6 and 12 months. At 12 months, the incidence of moderate to severe CPSP was 11.8% (95% CI 9.7 to 13.9) and of severe pain (NRS ≥6) 2.2% (95% CI 1.2 to 3.3). Signs of neuropathic pain were recorded in 35.4% (95% CI 23.9 to 48.3) and 57.1% (95% CI 30.7 to 83.4) of patients with moderate and severe CPSP, respectively. Functional impairment (BPI) at 6 and 12 months increased with the severity of CPSP (P 

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General anaesthetic agents do not influence persistent pain after breast cancer surgery: A prospective nationwide cohort study

BACKGROUND: It has recently been suggested that propofol exerts a protective effect on the occurrence of persistent pain after breast cancer surgery. We analysed data from a subcohort taken from a multicentre study to validate this information. OBJECTIVE: The objective of this article is to study the role of the agent used for maintenance of general anaesthesia on the occurrence of persistent pain, with adjustment for multiple pre and peri-operative variables using the generalised linear model. DESIGN: A prospective cohort study. SETTING: Four French university hospitals. PATIENTS: Three hundred and twenty-eight and 362 patients with full dataset, depending on the studied outcome. INTERVENTION: Questionnaires sent at the third and the sixth month after surgery. MAIN OUTCOME MEASURES: The risk of persistent postsurgical neuropathic pain (defined by the DN4 questionnaire) within 6 months after surgery, and the intensity of persistent pain at the sixth month. RESULTS: Axillary lymph node harvesting and previous history of peripheral neuropathy were independent risk factors of persistent postsurgical neuropathic pain, although older age was protective. The same independent risk factors, but not age, explained the intensity of persistent postsurgical pain at the sixth month after surgery. We did not find any effect of the general anaesthetic, whether halogenated agent or propofol, using either unadjusted or adjusted analyses based on covariates or propensity score. CONCLUSION: There does not appear to be a role for the anaesthetic protocol in the occurrence of persistent postsurgical pain. Other already well established hypotheses were confirmed. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT00812734).

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Neostigmine dose: Comparison between theory and practice

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Preoperative glycosylated haemoglobin as a predictor of postoperative analgesic requirements in diabetic patients: A prospective observational study

BACKGROUND: In diabetic individuals undergoing surgery, the analgesic effect of opioids on postoperative pain may be different from normal. Although the ability of glycosylated haemoglobin (HbA1c) to predict adverse events and outcomes after major surgery has recently been assessed, the ability of HbA1c to predict the need for postoperative analgesia has not been determined. OBJECTIVES: The objective of this study is to evaluate the relationship between preoperative glycaemic control in diabetic individuals and the opioid requirement for postoperative pain treatment. DESIGN: A prospective observational study. SETTING: Single university hospital. PATIENTS: Fifty-two diabetic patients undergoing open nephrectomy surgery. MAIN OUTCOME MEASURES: To evaluate the effect of long-term glucose control on postoperative analgesia requirements, the patients were divided into those with good glycaemic control (HbA1c

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Shoulder pain after hepatectomy occurs more frequently on the right side: A retrospective observational analysis

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Prevalence, characteristics and risk factors of chronic postsurgical pain after laparoscopic colorectal surgery: Retrospective analysis

BACKGROUND: The prevalence of chronic postsurgical pain (CPSP) is a critical medical problem with economic implications. Its prevalence after gastrointestinal surgery is not well documented, particularly when a laparoscopic approach is used. OBJECTIVE: The aim of the study was to determine the prevalence, the characteristics and the risk factors for CPSP after laparoscopic colorectal surgery. DESIGN: A retrospective analysis using a postal questionnaire. SETTING: The study was conducted at a university teaching hospital. PATIENTS: Patients who underwent laparoscopic colorectal surgery from April 2008 until December 2011 (n = 260). No epidural analgesia was used. MAIN OUTCOME MEASURES: Postoperative pain intensity, incidence and characteristics of CPSP, and impact on quality of life and sleep. RESULTS: Of 199 responses, 33 patients (17%) reported chronic pain at a median [interquartile range, IQR] of 38 [27 to 55] months after laparoscopic surgery with a median intensity of 4 [3 to 5]. CPSP had a negative impact on the quality of life in 84% of patients and on sleep in 43%. CPSP required regular analgesic(s) intake in 54% patients. Using a backward stepwise multivariate logistic regression model, the following variables were determined as independent risk factors for CPSP: redo surgery for anastomotic leakage (P = 0.01), inflammatory bowel disease (IBD) as the indication for surgery (P = 0.01) and preoperative pain (P = 0.05). CONCLUSION: The incidence of CPSP after laparoscopic colorectal surgery (17%) is similar to those reported in the literature after laparotomy. Risk factors are redo surgery for postoperative peritonitis, IBD and preoperative pain. TRIAL REGISTRATION: EudraCT 2012-005712-25.

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Intraoperative temperature monitoring with zero heat flux technology (3 M SpotOn sensor) in comparison with sublingual and nasopharyngeal temperature: An observational study: Erratum

No abstract available

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Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants

Objective: Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. Methods: We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All of the infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 8,87,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events (AEs). Results: Metoclopramide use increased from 1997 to 2005 and decreased from 2005 to 2012, whereas erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), whereas metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory AE during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs 76/19,001, 0.4%; P = 0.01), but odds were not significantly increased after adjusting for covariates (odds ratio 0.52, 95% confidence interval [CI] 0.26–1.02, P = 0.06). More infants experienced an AE while treated with metoclopramide than with erythromycin (odds ratio 1.21, 95% CI 1.03–1.43). Conclusions: Metoclopramide was associated with increased risk of AEs compared with erythromycin. Studies are needed to confirm safety and effectiveness of both the drugs in infants.

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Overuse of the Emergency Department and CT Scans in Pediatric IBD: Time for Hot Spotting?

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Infliximab More Effective in Therapy-Naïve Than in Therapy-Refractory Patients

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Portopulmonary Hypertension: Opportunities for Precision Pediatrics

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