Prevalence and Significance of Autoantibodies in Children with Acute Liver Failure.

Objectives: The purpose of this study is to estimate autoantibody (autoAB) frequency, clinical characteristics and 21 day outcome of participants in the Pediatric Acute Liver Failure Study Group (PALFSG) by ANA, SMA and LKM antibody status. Methods: AutoAB were determined at local and/or central laboratories. Subjects were assigned to autoimmune hepatitis (AIH), indeterminate and other diagnoses groups. Results: Between 1999 and 2010, 986 subjects were enrolled in the PALFSG. At least one autoAB result was available for 722 (73.2%). At least one autoAB was positive for 202 (28.0%). Diagnoses for autoAB+ subjects were: AIH (63), indeterminate (75) and other (64). AutoAB were more common in Wilson disease (12/32, 37.5%) vs other known diagnoses (52/253, 20.6%, p = 0.03). LKM+ subjects were younger (median 2.4 vs 9.1 yrs, p

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Factors Associated with Bleeding Secondary to Rupture of Esophageal Varices in Children and Adolescents With Cirrhosis.

Objective: Bleeding of esophageal varices is the main cause of morbidity and mortality in children with portal hypertension. It is important to understand the factors related with a bleeding episode to evaluate more effective primary prophylaxis. This study aims to describe the endoscopic and laboratory findings associated with upper gastrointestinal bleeding (UGIB) secondary to esophageal varices. Method: A cross-sectional study with 103 children and adolescents with cirrhosis, divided into a group that had experienced an episode of upper UGIB (35 patients) and a group without a history of UGIB (68 patients), was carried out. The esophageal and gastric varices were classified, and the portal hypertensive gastropathy, laboratory findings, and Child-Pugh classification were measured. Results: Factors observed in univariate analysis to be associated with UGIB were the presence of esophageal varices of medium caliber or larger, portal hypertensive gastropathy, presence of red spots on esophageal varices, Child-Pugh class B or C, and hypoalbuminemia (p

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There is No Iron in Human Milk.

No abstract available

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Incidence of Primary Mitochondrial Disease in Children Presenting With Acute Liver Failure Under 2 Years of Age.

Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important since liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF. Objective: To determine the incidence of MLD in children under two with ALF and the utility of routine investigations to detect MLD. Methods: Thirty-nine consecutive infants with ALF were admitted to a single unit from 2009-11. All were extensively investigated using an established protocol. Genes implicated in MDS were sequenced in all cases and tissue mtDNA copy number measured where available. Results: Five infants (17%) had genetically proven MLD: DGUOK (n = 2), POLG (n = 2) and MPV17 (1). Four of these died whilst one recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease following LT while five who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD. Conclusions: Low liver mtDNA copy number may be a secondary phenomenon in ALF. Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first two years of life. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Keeping an Eye on Noisy Movements: On Different Approaches to Perceptual-Motor Skill Research and Training

Abstract

Contemporary theorizing on the complementary nature of perception and action in expert performance has led to different emphases in the study of movement coordination and gaze behavior. On the one hand, coordination research has examined the role of variability in movement control, evidencing that variability facilitates individualized adaptations during both learning and performance. On the other hand, and at odds with this principle, the majority of gaze behavior studies have tended to average data over participants and trials, proposing the importance of universal 'optimal' gaze patterns in a given task, for all performers, irrespective of stage of learning. In this article, we discuss new lines of inquiry with the aim of reconciling these two distinct approaches. We consider the role of inter- and intra-individual variability in gaze behaviors and suggest directions for future research.

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Explosive Training and Heavy Weight Training are Effective for Improving Running Economy in Endurance Athletes: A Systematic Review and Meta-Analysis

Abstract

Background

Several strategies have been used to improve running economy (RE). Defined as the oxygen uptake required at a given submaximal running velocity, it has been considered a key aerobic parameter related to endurance running performance. In this context, concurrent strength and endurance training has been considered an effective method, although conclusions on the optimal concurrent training cannot yet be drawn.

Objective

To evaluate the effect of concurrent training on RE in endurance running athletes and identify the effects of subject characteristics and concurrent training variables on the magnitude of RE improvement.

Methods

We conducted a computerized search of the PubMed and Web of Science databases, and references of original studies were searched for further relevant studies. The analysis comprised 20 effects in 16 relevant studies published up to August 2015. The outcomes were calculated as the difference in percentage change between control and experimental groups (% change) and data were presented as mean ± 95 % confidence limit. Meta-analyses were performed using a random-effects model and, in addition, simple and multiple meta-regression analyses were used to identify effects of age, training status, number of sessions per week, training duration, type of strength training, and neuromuscular performance on % change in RE.

Results

The concurrent training program had a small beneficial effect on RE (% change = −3.93 ± 1.19 %; p < 0.001). In addition, explosive (% change = −4.83 ± 1.53; p < 0.001) and heavy weight (% change = −3.65 ± 2.74; p = 0.009) training programs produced similar improvements in RE, while isometric training (% change = −2.20 ± 4.37; p = 0.324) in selected studies did not induce a significant effect. The multiple linear meta-regression analysis showed that all the differences between % changes could be explained by including the above-mentioned characteristics of subjects and weight training program elements. This model showed that the magnitude of the % change in RE was larger for longer training duration (β = −0.83 ± 0.72, p = 0.02).

Conclusion

Explosive training and heavy weight training are effective concurrent training methods aiming to improve RE within a few weeks. However, long-term training programs seem to be necessary when the largest possible improvement in RE is desired.

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Influence of chronic endurance exercise training on conduit artery retrograde and oscillatory shear in older adults

Abstract

Purpose

With aging, there tends to be an increase in retrograde and oscillatory shear in peripheral conduit arteries of humans. Whether the increase in shear rate is due to the aging process or an effect of a less active lifestyle that often accompanies aging is unknown. Therefore, we examined whether chronic endurance exercise training attenuates conduit artery retrograde and oscillatory shear in older adults.

Methods

Brachial and common femoral artery mean blood velocities and diameter were determined via Doppler ultrasound under resting conditions, and shear rate was calculated in 13 young (24 ± 2 years), 17 older untrained (66 ± 3 years), and 16 older endurance exercise-trained adults (66 ± 7 years).

Results

Brachial artery retrograde (−9.1 ± 6.4 vs. −12.6 ± 9.4 s⁻¹; P = 0.35) and oscillatory (0.14 ± 0.08 vs. 0.14 ± 0.08 arbitrary units; P = 0.99) shear were similar between the older trained and untrained groups, whereas brachial artery retrograde and oscillatory shear were greater in older untrained compared to young adults (−5.0 ± 3.4, 0.08 ± 0.05 s⁻¹ arbitrary units, P = 0.017 and 0.048, respectively). There was no difference between the young and older trained brachial retrograde (P = 0.29) and oscillatory (P = 0.07) shear. Common femoral artery retrograde (−6.3 ± 2.9 s⁻¹) and oscillatory (0.21 ± 0.08 arbitrary units) shear were reduced in older trained compared to the older untrained group (−10.4 ± 4.1 and 0.30 ± 0.09 s⁻¹ arbitrary units, both P = 0.005 and 0.006, respectively), yet similar to young adults (−7.1 ± 3.5 and 0.19 ± 0.06 s⁻¹ arbitrary units, P = 0.81 and 0.87, respectively).

Conclusion

Our results suggest that chronic endurance exercise training in older adults ameliorates retrograde and oscillatory shear rate patterns, particularly in the common femoral artery.

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EP 16. Nucleus accumbens stimulation in severe obsessive compulsive disorder

Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and often bears a high level of suffering and a great impact on psychosocial functioning and quality of life. International guidelines agree on cognitive behavioural therapy and pharmacological interventions as first line treatments. Only 70% of patients with OCD respond to these treatments, a substantial proportion of patients remain severely affected, for these patients deep brain stimulation of the nucleus accumbens (NAcc-DBS) might be a useful neuromodulative therapy approach.

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7. Thalamic mechanisms in the generation and modulation of the cortical slow oscillation in mice

It is well established that thalamus plays a crucial role in the generation of the synchronous slow oscillation in the cortex during non-REM sleep. The slow/delta power (0.2–4Hz) is the main measured factor of the quality of sleep. However, the contribution of different thalamic nuclei to the inception of the slow wave activities and its synchronization is not known. We hypothesized that the first-order (specific) thalamic nuclei provide a control of slow waves in primary cortical areas, while higher-order (non-specific) thalamic nuclei may synchronize the slow-wave activities across wide cortical regions.

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31. Intraoperative monitoring of motor cranial nerves and cranial nerve nuclei

Intraoperative neurophysiologic monitoring of cranial nerve function is primarily performed in those cranial nerves whose function has a motor component. The rationale, as well as the stimulation and recording techniques employed, is similar to that used in assessing the functional integrity of motor peripheral nerves. The primary difference is in the placement of the recording electrodes and the neural structures that are at risk for injury. In addition, cranial nerve dysfunction is not solely confined to a cranial nerve but can also involve the nucleus of the specific nerve.

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EP 44. Treatment perspectives using deep brain stimulation in patients with Parkinson’s Disease in the Republic of Moldova

Given the large number of patients with Parkinson's Disease (PD), high rate of failure of modern medical treatment and the lack of this method of treatment in Republic of Moldova at present, we proposed to analyse the treatment perspectives using Deep Brain Stimulation (DBS) in patients with PD and determine candidates for it based on the patients database of the national Institute of Neurology and Neurosurgery.

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15. Aortic IOM for thoraco-abdominal aneurysm surgery

In this presentation, I will give an overview of why and how intraoperative neurophysiologic techniques help reducing post-operative neurologic deficit in Aortic surgery. I will start by briefly presenting the vascular anatomy of the spinal cord as well as of the main types of Aortic aneurysms, surgical repair procedures (i.e., open TAA repair with distal aortic perfusion and endovascular repair/TEVAR) and their associated neurological risks. I will continue with integrating the intraoperative neurophysiologic techniques within the main methods used for intraoperative neuroprotection that allow reaching the balance between metabolic demand of the spinal cord and its oxygen supply.

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EP 65. DBS-induced alpha desynchronization in the subthalamic nucleus of PD patients

Deep brain stimulation of the subthalamic nucleus (STN DBS) has developed into a standard therapy for treatment refractory stages of Parkinson's disease (PD). Oscillatory components play an important role in the functioning of the brain through the control of neuronal firing (Engel and Fries, 2010). The power of the beta-band (12–30Hz) in the STN is an informative biomarker for PD. It is reduced under L-Dopa medication and DBS (Kühn et al., 2008; Bronte-Stewart et al., 2009). However, the impact of DBS onto other oscillatory components and their relevance as PD biomarkers is less explored (Rosa et al., 2014; Beudel and Brown, 2016).

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23. Transcranial magnetic stimulation (TMS) in neurological diseases

The use transcranial magnetic stimulation (TMS) in clinical settings has grown over the last three decades. Since its introduction by Barker in 1985, TMS has been used to assess central motor pathways, as well as cortical function and intrinsic circuitry. Single-pulse TMS can map motor cortical outputs, and with cervical, thoracic and lumbar spinal cord stimulation, one can study the central motor conduction time. In addition, TMS document cortical hyperexcitability, as in early phases of sporadic ALS, or hypo excitability as in ischemic infarcts or central demyelinating diseases.

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7. Evidence-based guideline of intraoperative spinal monitoring with SSEP & TcMEP

Evidence-based guidelines assist patients, physicians and carriers to determine which techniques are of established value to improve outcome. The Institute of Medicine recommends processes by which literature is assessed as evidence of effectiveness on achieving improved outcome. Following such guidance, assessment of spinal cord monitoring demonstrates an established value to alert the surgical team to adverse changes. Based on those alerts, the guidelines recommend that the surgical team take action to identify and reverse the cause of adverse changes.

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EP 78. Probabilistic imaging of motor projections of dentate nucleus as target structure for deep brain stimulation in tremor

As previously described (Coenen et al., 2014; Coenen et al., 2011), deep brain stimulation of dentate-rubro-thalamo-(cortical) (DRT(C)) pathway, efferent motor projection of dentate nucleus, leads to improvement of tremor symptoms. Visualization of DRT (C), as proposed by several authors (Coenen et al., 2011; Keser et al., 2015), reconstructs connections between dentate nucleus (DN) and ruber nucleus (RN) using deterministic diffusion tensor tractography. However tracer primate studies show that motor projections read spread more than classically described pathway in ruber nucleus (Dum and Strick, 2003).

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EP 54. Modeling the effects of current steering with directional leads

Deep brain stimulation (DBS) systems differ in designs and stimulation abilities. New developments in DBS are focusing on enabling directional stimulation capabilities that may possibly activate targets with greater specificity. We sought to use computational modeling to demonstrate that combining directional leads with Multiple Independent Current Control (MICC) may offer additional control over the shape of the Volume of Tissue Activated (VTA) using proposed lead designs from three different manufacturers.

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27. Selective dorsal rhizotomy: Fixed or flexible criteria?

Spasticity in cerebral palsy results from decreased descending influence on segmental spinal synapses. Since most descending effects are inhibitory, the net result is loss of inhibition and hyperactive reflexes, leading to spasticity and abnormal gait. The aim of selective dorsal rhizotomy is to spare all motor rootlets and to section only the sensory rootlets showing the most evidence of lack of inhibition. Ideally, this results in a decrease in reflex hyperactivity while avoiding gross sensory or motor deficits, leading to improved functional status.

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19. Transcraneal magnetic stimulation

Transcranial magnetic stimulation (TMS) a relatively young technique, described 30years ago as a non-invasive means of stimulating the cerebral cortex, and has proved to be a unique tool for probing brain-behavior relationships. First described as a diagnostic resource, therapeutic role for rTMS in neuropsychiatry has been demonstrated in diverse neuroscience areas. We review studies on the mechanisms of action of rTMS, and present a summary of the news applications of TMS in basic neuroscience.

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11. Intraoperative electrocorticography (ECOG) For seizure focus localization

In this lecture, I will give an overview of different uses of Intraoperative ECoG. I will start with presenting examples of epilepsy surgery cases and clinical scenarios where ECoG recordings help delineating the epileptic focus/foci, such as in: 1 – intractable epilepsy from suspected highly epileptogenic lesion( e.g., cortical dysplasia) in patients at high risk of complications from phase II invasive recordings; 2 – use of ECoG in anterior temporal lobectomies; 3– differentiating between a temporal versus orbitofrontal focus; 4 – surgical management of status epilepticus; 5 – determining unifocal versus multifocal epilepsy in widespread pathology; 6 – use of ECoG in tuberous sclerosis epilepsy.

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2. Communication in the OR between surgeon, neurophysiologists, and anesthesiologists

The operating room can be a high stress environment in which even minor mistakes may have major consequences. A key to successful management of the patient and their disease is excellent, timely communication involving all the caregivers in the room. One area that highlights this need is during intraoperative neurophysiological monitoring. Knowledge of anesthetic and surgical effects on neurophysiology is imperative, as is the understanding of the strengths and limitations of the various monitoring techniques.

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3. Daily dynamics of states of vigilance in mice

Previous studies demonstrated that (a) mice preferentially sleep during light hours and they are preferentially awake during dark hours; (b) mice have fragmented sleep. Despite multiple investigations involving sleep-wake transitions in mice, the exact patterns of sleep-wake alternations are not known. Here we studied sleep-wake pattern distribution in 5 young adult C57BL/6 mice over 5 days using continuous LFP and EMG recordings with a resolution of 5s. The states were automatically detected based on LFP delta power, theta power and EMG power.

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EP 71. Single cell firing patterns in the anterior nucleus of the thalamus relate to therapy response in deep brain stimulation for refractory epilepsy

Patients with medically refractory epilepsy treated with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) vary highly in their therapy response. Proper positioning of the DBS lead is crucial to maximize efficacy and minimize side effects. For a correct implantation, the ANT is anatomically located using pre-operative 3T MRI and perioperative microelectrode recordings (MER). Neurons in the ANT have highly variable, yet characteristic patterns of firing in bursts. During DBS lead implantation, we noted differences among patients' characteristic burst patterns along the electrode trajectory.

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EP 60. Bicycling suppresses beta power more strongly than walking in the subthalamic nucleus of Parkinsonian patients

Walking abilities are severely affected in patients suffering from Freezing of Gait (FOG), a common phenomenon in advanced Parkinson's disease (PD). Despite the high occurrence of the symptom in the progression of the disease, little is known about the underlying mechanisms. Remarkably, it was recently reported that patients with FOG are still able to ride a bike (Snijders et al., 2011; Snijders et al., 2012). While similar brain networks are involved in walking and bicycling (Fukuyama et al., 1997; Christensen et al., 2002), it is not understood why both types of movement are differently affected in patients with FOG.

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EP 48. Effects of thalamic deep brain stimulation on spontaneous language production

The thalamus is thought to contribute to language-related functions, but specifications of this notion remain vague.

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33. Special characteristics of cortical motor mapping in children

Direct Cortical Stimulation (DCS) for motor mapping and monitoring has special characteristics in children. Several physiological, pathological, and pharmacological factors determine higher cortical motor thresholds (CMT) in this population. It is known that physiological CMT to electrical or magnetic stimulation progressively decrease from the first months of life reaching adult values at about the age of 18years. Certain pathological conditions such as errors in neuronal migration, dysembryoplastic neuroepithelial tumor, cortical dysplasia, and retro-rolandic low grade glioma may further increase CMT.

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29. Physiopathogenic mechanisms in attention deficit disorder (ADD)

Diagnosing and treating ADD are major challenges nowadays, as much as when introduced in the DSMIII and after two centuries studying inattention, its core symptom, as a brain dysfunction. Such relentless could result from neglecting the high complexity of dynamically interacting mechanisms. Aside cultural and environmental factors, the complexity becomes obvious at the neurophysiology lab. We wanted to investigate differences in neurophysiological patterns that could help our understanding of physiopathogenic mechanisms, and to use that understanding while planning therapeutic interventions.

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The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals

Objectives: We examined whether a functional variant of the ADRA1A gene moderated cocaine-induced subjective effects in a group of cocaine-dependent individuals. Methods: This study was a within-participant, double-blind, placebo-controlled inpatient human laboratory evaluation of 65 nontreatment-seeking, cocaine-dependent [Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)] individuals aged 18–55 years. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min before receiving an infusion and at 5 min intervals for the subsequent 20 min. The rs1048101 variant of the α1A-adrenoceptor (ADRA1A) gene was genotyped and it was evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) moderated the magnitude of the subjective effects produced by cocaine. Results: Thirty (46%) participants were found to have the major allele CC genotype and 35 (44%) carried at least one minor T-allele of rs1048101 (TT or TC genotype). Individuals with the CC genotype showed greater responses for 'desire' (P

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Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles

Objectives: Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (−) AAB titres and in AIH patients. Methods: High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Results: Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P=3.7E−13/corrected P-value (Pc)=1.0E−11], C*07:01 (46 vs. 24%, P=6.4E−04/Pc=0.012), DRB1*03:01 (58 vs. 21.5%, P=5.0E−09/Pc=1.0E−07) and DQB1*02:01 (56 vs. 22%, P=6.8E−08/Pc=9.0E−07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P=0.02/Pc=0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB+ compared with DILI AAB− (13.8 vs. 4.0%, P=0.02/Pc=0.5; 13.8 vs. 4.7%, P=0.04/Pc=0.5). Conclusion: The presence of HLA alleles B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 and possibly A*01:01 enhances the risk of AIH (type 1) in Spanish patients. These alleles form part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05:03 could potentially increase the risk of positive AAB (particularly antinuclear antibody) in Spanish DILI patients.

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Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis

Objective: Although the reduced function of the cytochrome P450 2D6*10 (CYP2D6*10) allele is common among Asian populations, existing evidence does not support paroxetine therapy adjustments for patients who have the CYP2D6*10 allele. In this study, we attempted to evaluate the degree of the impact of different CYP2D6 genotypes on the pharmacokinetic (PK) variability of paroxetine in a Japanese population using a population PK approach. Methods: This retrospective study included 179 Japanese patients with major depressive disorder who were being treated with paroxetine. CYP2D6*1, *2, *5, *10, and *41 polymorphisms were observed. A total of 306 steady-state concentrations for paroxetine were collected from the patients. A nonlinear mixed-effects model identified the apparent Michaelis–Menten constant (Km) and the maximum velocity (Vmax) of paroxetine; the covariates included CYP2D6 genotypes, patient age, body weight, sex, and daily paroxetine dose. Results: The allele frequencies of CYP2D6*1, *2, *5, *10, and *41 were 39.4, 14.5, 4.5, 41.1, and 0.6%, respectively. There was no poor metabolizer who had two nonfunctional CYP2D6*5 alleles. A one-compartment model showed that the apparent Km value was decreased by 20.6% in patients with the CYP2D6*10/*10 genotype in comparison with the other CYP2D6 genotypes. Female sex also influenced the apparent Km values. No PK parameters were affected by the presence of one CYP2D6*5 allele. Conclusion: Unexpectedly, elimination was accelerated in individuals with the CYP2D6*10/*10 genotype. Our results show that the presence of one CYP2D6*5 allele or that of any CYP2D6*10 allele may have no major effect on paroxetine PKs in the steady state.

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HLA-Cw6 allele, NFkB1 and NFkBIA polymorphisms play no role in predicting response to etanercept in psoriatic patients

Objective: This retrospective study aimed to evaluate the role of NFKB1-94 insertion/deletion ATTG (rs28362491) and NFkBIA 2758 A>G (rs696) polymorphisms and HLA-Cw6 allele in predicting the response to etanercept, a TNF-α blocker, in a population of psoriatic patients naive to biologics. Methods: Genomic DNA was extracted from whole blood in a series of 96 psoriatic patients who received etanercept for at least 3 months. Patients were classified as responders if they achieved a Psoriasis Area and Severity Index improvement of at least 75% after 12 weeks of etanercept treatment and as nonresponders if Psoriasis Area and Severity Index improvement was less than 75%. Genotyping was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Results: We did not find any significant role of NFKB1-94 insertion/deletion ATTG (rs28362491) and NFkBIA 2758 A>G (rs696) polymorphisms and the HLA-Cw6 allele in predicting the response to etanercept. Conclusion: Our findings suggest that NFKB1 and NFkBIA polymorphisms are not related to the response to etanercept. They also indicate that the therapeutic response to etanercept is not influenced by the presence of the HLA-Cw6 allele, in contrast with previous evidence on ustekinumab, suggesting that such an association is related more to drug than to disease characteristics.

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PharmGKB summary: isoniazid pathway, pharmacokinetics

No abstract available

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Man struck by car treated by paramedic he stole from

By Nassim Benchaabane
The St. Louis Post-Dispatch

ST. LOUIS — A paramedic with the St. Louis Fire Department reported his car broken into and possessions stolen Thursday night — only to find them minutes later as he helped a man who had been hit by car.

Firefighters at a station in the Central West End had noticed the lights were on in a car in the parking lot, fire Capt. Gregg Favre said. After investigating, they found the car had been broken into. The paramedic who owned the car filed a report with police about the break-in and the theft of possessions that has been inside.

Fifteen minutes later, the paramedic was among the first responders to a call about a pedestrian struck by a car in the 5500 block of Page Avenue in north St. Louis.

At that scene, the paramedic saw something that looked familiar — his gym bag and other personal possessions — laying next to the man who had been hit.

The paramedic eventually filed a second report with police — but only after he provided medical treatment to the man, whose condition was stable after the incident, Favre said.

"He made sure this was not a life-threatening situation first," Favre said. "He put his duty as a paramedic before anything else."

Police on Friday night did not have any details about whether charges were filed in the car break-in or about the accident in which the man was struck.

Copyright 2016 the St. Louis Post-Dispatch

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Effect of endovenous lidocaine on analgesia and serum cytokines: double-blinded and randomized trial

This trial aimed to compare postoperative analgesia, opioid consumption, duration of ileus and hospital stay, and cytokine levels in patients undergoing laparoscopic cholecystectomies who received intravenous lidocaine in comparison with a control group.

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Microglial role in the development of chronic pain.

Purpose of review: The review aims to present the latest research into microglia and their role in pain. Recent findings: Microglia affect sex and age-dependent differences in pain. The various microglial phenotypes make their involvement in pain more complex but provide more potential as pain modulators. Summary: Glial cells, composed of microglia, astrocytes, and oligodendrocytes, outnumber neurons in the central nervous system. The crosstalk between these cells and neurons is now established as participating in the development of chronic pain. There has been a great advance in the description of microglia reactivity from pro to anti-inflammatory phenotypes. The modulation of these phenotypes could be a potential target for pain therapy. Recently, different microglial reactivity between man and woman and between neonates and adults, in response to nerve injury were described, which could explain some of the sex differences in pain sensitivity and the absence of neuropathic pain development in neonates. Clinical trials using microglia as a target have been carried out in various neurological diseases and pain, with limited efficacy in the latter, but there are nonetheless, indications that with some improvement in study strategies microglia could be a future target for pain control. Copyright (C) 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The Importance of Having Sulfur

Publication date: Available online 5 August 2016
Source:Journal of Genetics and Genomics
Author(s): Anna Koprivova, Stanislav Kopriva
Sulfur is an essential nutrient for all living organisms. Plants take up inorganic sulfate from soil, reduce it, and incorporate into cysteine which is a source of reduced sulfur for other cellular components. Among them the amino acid methionine is of great importance as it is essential for animal and human nutrition. Sulfate assimilation pathway and its control are well understood on the physiological level. The bulk of knowledge on the regulation of the pathway, however, has been derived from the model plant Arabidopsis. Given the importance of sulfur for crop yield and quality, this review will summarize the knowledge of sulfur metabolism in crop plants and will discuss how manipulation of sulfur metabolism can help to improve crop productivity.



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Molecular insights of organochlorine biocide-induced toxicity in zebrafish: Whole-adult-organism toxicogenomics, targeted gene expression and histological analyses

Publication date: Available online 5 August 2016
Source:Journal of Genetics and Genomics
Author(s): Eei Yin Lui, Caixia Li, Zhi-Hua Li, Zhiyuan Gong, Siew Hong Lam




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Examining the Washington State Breastfeeding-Friendly Policy Development Process Using the Advocacy Coalition Framework

Abstract

Objectives Breastfeeding promotion is increasingly recognized as a key public health strategy. Policies can promote breastfeeding by creating supportive environments and addressing challenges. In 2014, the Washington State legislature considered bills to create a voluntary recognition system for breastfeeding-friendly hospitals, clinics, worksites and childcare settings. These Breastfeeding-Friendly Washington (BFW) bills (SB 6298 and HB 2329) did not pass. Methods The purpose of this case study was to analyze the policy development process for the BFW bills using the Advocacy Coalition Framework. Data were collected through semi-structured interviews with key stakeholders in the state policy process, and document review. We used thematic analysis to identify deductive and inductive themes. Results Though all policy actors indicated general support for breastfeeding, two main coalitions (proponents and opponents) diverged in their support of the BFW bills as policy solutions to address barriers to breastfeeding. We conducted 29 interviews with mainly bill proponents, and 54 documents confirmed data about bill opponents. Proponents supported the bills given increasingly strong evidence of breastfeeding's benefits and that public policy could address environmental challenges to breastfeeding. Opponents saw the bills as government overreach into the private matter of choosing to breastfeed. Opposition to the bills came late in the session, and proponents felt opponents' messaging misconstrued the intent of the legislation. Conclusions for Practice Key learnings for developing breastfeeding-friendly state policies include analyzing differences between proponents' and opponents' beliefs, framing advocacy messages beyond individuals and health, expanding the coalition outside of traditional health entities, and anticipating the opposition.

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IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome

Publication date: Available online 5 August 2016
Source:Mutation Research/Reviews in Mutation Research
Author(s): Zvi Laron, Rivka Kauli, Lena Lapkina, Haim Werner
Laron syndrome (LS) is a unique model of congenital IGF-I deficiency. It is characterized by dwarfism and obesity, and is caused by deletion or mutations of the growth hormone receptor (GH-R) gene. It is hypothesized that LS is an old disease originating in Indonesia and that the mutated gene spread to South Asia, the Middle East, the Mediterranean region and South America.



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Molecular mechanisms underlying human papillomavirus E6 and E7 oncoprotein-induced cell transformation

Publication date: Available online 5 August 2016
Source:Mutation Research/Reviews in Mutation Research
Author(s): Suruchi Mittal, Lawrence Banks
Human papillomaviruses (HPVs) are the causative agents of 5% of all



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Biomarkers of acute appendicitis: systematic review and cost–benefit trade-off analysis

Abstract

Background

Acute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed to evaluate the clinical utility of individual biomarkers in the diagnosis of appendicitis and appraise the quality of these studies.

Methods

A systematic review of the literature between January 2000 and September 2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted. Studies in which the diagnostic accuracy, statistical heterogeneity and predictive ability for severity of several biomarkers could be elicited were included. Information regarding costs and process times was retrieved from the regional laboratory. European surgeons blinded to these reviews were independently asked to rank which characteristics of biomarkers were most important in acute appendicitis to inform a cost–benefit trade-off. Sensitivity testing and the QUADAS-2 tool were used to assess the robustness of the analysis and study quality, respectively.

Results

Sixty-two studies met the inclusion criteria and were assessed. Traditional biomarkers (such as white cell count) were found to have a moderate diagnostic accuracy (0.75) but lower costs in the diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6 and urinary 5-HIAA) were found to have high process-related costs including analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed significant potential biases in the literature.

Conclusion

When assessing biomarkers, an appreciation of the trade-offs between the costs and benefits of individual biomarkers is needed. Further studies should seek to investigate new biomarkers and address concerns over bias, in order to improve the diagnosis of acute appendicitis.

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Increasing resident utilization and recognition of the critical view of safety during laparoscopic cholecystectomy: a pilot study from an academic medical center

Abstract

Background

Laparoscopic cholecystectomy (LC) is a commonly performed surgical procedure; however, it is associated with an increased rate of bile duct injury (BDI) when compared to the open approach. The critical view of safety (CVS) provides a secure method of ductal identification to help avoid BDI. CVS is not universally utilized by practicing surgeons and/or taught to surgical residents. We aimed to pilot a safe cholecystectomy curriculum to demonstrate that educational interventions could improve resident adherence to and recognition of the CVS during LC.

Methods

Forty-three general surgery residents at Thomas Jefferson University Hospital were prospectively studied. Fifty-one consecutive LC cases were recorded during the pre-intervention period, while the residents were blinded to the outcome measured (CVS score). As an intervention, a comprehensive lecture on safe cholecystectomy was given to all residents. Fifty consecutive LC cases were recorded post-intervention, while the residents were empowered to "time-out" and document the CVS with a doublet photograph. Two independent surgeons scored the videos and photographs using a 6-point scale. Residents were surveyed pre- and post-intervention to determine objective knowledge and self-reported comfort using a 5-point Likert scale.

Results

In the 18-week study period, 101 consecutive LCs were adequately captured and included (51 pre-intervention, 50 post-intervention). Patient demographics and clinical data were similar. The mean CVS score improved from 2.3 to 4.3 (p < 0.001). The number of videos with CVS score >4 increased from 15.7 to 52 % (p < 0.001). There was strong inter-observer agreement between reviewers. The pre- and post-intervention questionnaire response rates were 90.7 and 83.7 %, respectively. A greater number of residents correctly identified all criteria of the CVS post-intervention (41–93 %, p < 0.001) and offered appropriate bailout techniques (77–94 %, p < 0.001). Residents strongly agreed that the CVS education should be included in general surgery residency curriculum (mean Likert score = 4.71, SD = 0.54). Residents also agreed that they are more comfortable with their LC skills after the intervention (4.27, σ = 0.83).

Conclusion

The combination of focused education along with intraoperative time-out significantly improved CVS scores and knowledge during LC in our institution.

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Preventing anastomotic complications: early results of laparoscopic gastric devascularization two weeks prior to minimally invasive esophagectomy

Abstract

Background:

Laparoscopic gastric devascularization (LGD) is an innovative method to improve gastric conduit perfusion and improve anastomotic healing following esophagectomy. This study reports our early experience with LGD performed two weeks prior to minimally invasive esophagectomy (MIE) with intrathoracic anastomosis.

Methods:

We performed a retrospective review of all patients who underwent LGD prior to minimally invasive Ivor Lewis esophagectomy between August 2014 and July 2015 at a large academic medical center. LGD included staging laparoscopy with division of the short gastric vessels, left gastric artery and coronary vein, and posterior gastric attachments. Patient demographics, comorbid conditions, clinical stage, use of neoadjuvant chemoradiation, perioperative events, length of hospital stay, 60-day readmission, and complications were collected and analyzed.

Results:

Thirty patients underwent LGD prior to minimally invasive Ivor Lewis esophagectomy, and 21 (70 %) received neoadjuvant chemoradiation. LGD was performed a median of 14.5 (9–42) days prior to esophagectomy. Median operative time was 39 (18–56) minutes, and median length of stay was 0 (0–1) days. There were no complications or readmissions following LGD. MIE was completed laparoscopically in 93 % of patients; two patients required conversion to an open procedure due to mediastinal inflammation following neoadjuvant chemoradiation. Five patients (17 %) were readmitted within 60 days of surgery: one (3 %) patient with an anastomotic leak, two (7 %) with pneumonia, and two (7 %) with post-operative nausea and vomiting. One patient (3 %) expired following an anastomotic leak that required reoperation, and no patients developed an anastomotic stricture during the study period.

Conclusions:

LGD with delayed esophageal resection and reconstruction can be safely performed two weeks prior to MIE with minimal morbidity. The low rate of anastomotic leak (3 %) and absence of anastomotic strictures in this series suggest that this approach may successfully improve gastroesophageal anastomotic healing and reduce the rate of anastomotic complications reported with single-stage approaches.

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Risk factors associated with difficult gastric endoscopic submucosal dissection: predicting difficult ESD

Abstract

Background and study aim

Endoscopic submucosal dissection (ESD) is a widely accepted treatment for superficial gastric neoplasms. Difficult ESD can lead to complications, such as bleeding and perforation. To predict difficult ESD procedures, we analyzed the factors associated with difficult ESD.

Patients and methods

The medical records of 1052 ESD procedures were retrospectively reviewed. Difficult ESD was defined by any one of three end points: longer procedure time (≥60 min), piecemeal resection, incomplete (R1) resection, or gastric wall perforation. To determine the factors associated with difficult ESD, clinical and pathologic features and endoscopic findings were analyzed.

Results

The rates of en bloc resection and curative (R0) resection were 93.3 and 92.4 %, respectively. The mean procedure time was 27.7 ± 16.7 min. After multivariate analysis, larger tumor size (≥20 mm) was an independent risk factor for longer procedure time (OR 4.1, P < 0.001), for piecemeal resection (OR 2.3, P = 0.003) and incomplete (R1) resection (OR 2.1, P = 0.005). Location of the lesion (upper third) was an independent risk factor for longer procedure time (OR 5.8, P < 0.001), for piecemeal resection (OR 4.1, P < 0.001) and incomplete (R1) resection (OR 4.5, P < 0.001). Submucosal fibrosis was an independent risk factor for longer procedure time (OR 9.7, P < 0.001), for piecemeal resection (OR 2.4, P < 0.001) and incomplete (R1) resection (OR 2.6, P < 0.001). Finally, submucosal invasive gastric cancer was an independent risk factor for piecemeal resection (OR 2.6, P = 0.008), for perforation (OR 19.3, P = 0.001) and for incomplete (R1) resection (OR 2.7, P = 0.001).

Conclusions

Difficult ESD procedures are a function of the lesion size and location, submucosal fibrosis, and submucosal invasive cancer. When a difficult ESD procedure is expected, appropriate preparations should be considered, including consultation with more experienced endoscopists.

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A new experimental model of calculous cholecystitis suitable for the evaluation and training of minimally invasive approaches to cholecystectomy

Abstract

Background

Novel, less invasive approaches such as single-incision laparoscopic cholecystectomy or natural orifice transluminal endoscopic surgery require preclinical evaluation and training. Therefore, there is a need for an experimental model closely mimicking the clinical situation. The aim of our study was to create an experimental model of calculous cholecystitis in a large laboratory animal and test its feasibility for the evaluation of different techniques of cholecystectomy.

Methods

In 11 laboratory pigs, gallstones were placed inside the gallbladder laparoscopically. Levels of inflammatory markers—leucocytes (WBC), C-reactive protein (CRP) and interleukin 6 (IL-6)—were monitored on the postoperative days (POD) 1, 2, 3, 7 and 30. Abdominal ultrasound was performed 2 and 4 weeks after the operation. Four weeks after the lithiasis induction, laparoscopic cholecystectomy was performed. The control group consisted of ten healthy animals in which a cholecystectomy was performed. The pigs were monitored for 30 days after surgery. All removed gallbladders were assessed histologically.

Results

The induction of lithiasis took 42 (35–52) min with no morbidity and mortality. The values of WBC, CRP and IL-6 increased significantly (vs. baseline) on POD 1, 2 and 3 (p < 0.05) and then normalised. Ultrasonography confirmed the presence of chronic calculous cholecystitis in all cases after 4 weeks. Laparoscopic cholecystectomy was significantly longer in animals with lithiasis, 63 (42–91) versus 46 (31–62) min (p = 0.018). Perioperative gallbladder wall perforation was significantly more frequent in the model group (8/11 vs. 1/10; p = 0.04). In contrast to healthy animals, all gallbladders with stones showed histological signs of chronic inflammation.

Conclusions

A new animal model of calculous cholecystitis was created. Laparoscopic cholecystectomy was more technically difficult compared to operating on a healthy gallbladder. This model may be a suitable tool for effective preclinical training and also for the evaluation of different techniques of cholecystectomy.

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Outcomes of concomitant ventral hernia repair performed during bariatric surgery

Abstract

Background

Currently there is no consensus on management of ventral hernias encountered during bariatric surgery (BS). This study aims to evaluate the incidence and outcomes of concomitant ventral hernia repair (VHR) during BS at our institution.

Methods

Patients who had concomitant VHR during BS from 2004 to 2015 were identified. Data collected included baseline demographics, comorbidities, perioperative parameters, surgical approach and postoperative outcomes.

Results

A total of 159 patients underwent concomitant VHR during the study period at the time of BS. One hundred and one (64 %) patients were female; median age was 53 years (IQR 45.0–60.3) and median BMI was 48.2 kg/m² (IQR 41.6–54.1). Comorbidities included: hypertension (n = 124, 78 %), type 2 diabetes (n = 103, 65 %), hyperlipidemia (n = 100, 63 %), obstructive sleep apnea (n = 98, 62 %) and reflux disease (n = 54, 34 %). Out of 159 patients, 41 patients (26 %) had a prior VHR. Out of 103 patients, 69 patients (67 %) had a previous abdominal surgery. Of the concomitant VHR, 144 (91 %) were completed laparoscopically, 12 (7 %) patients were converted to open surgery and 3 (2 %) patients underwent primary open procedures. Technique included primary suture closure in 115 (72 %) and mesh repair in 44. Early postoperative complications (<30 days) were reported in 16 (10 %) patients, with superficial wound infection (n = 9), bowel obstruction (n = 2), marginal ulcer (n = 2), DVT (n = 1) and pneumonia (n = 1). Hernia recurrence was reported in 3 patients (2 %) in the early post-op period and in 40 patients (25 %) as a late (>30 days) complication. Surgery for recurrent hernia was performed in 31/42 patients during follow-up. At 12-month follow-up, median BMI and % excess weight loss were 34.2 kg/m² (IQR 29.5–40.9) and 59.6 % (IQR 44.9–74.8 %), respectively.

Conclusion

Ventral hernia is a common finding in patients undergoing BS. Both primary suture repair and mesh repair result in acceptable results, both in terms of recurrence and perioperative complications.

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Robotic-assisted ventral hernia repair: a multicenter evaluation of clinical outcomes

Abstract

Background

The open approach continues to be widely performed for ventral hernia repair, while the minimally invasive laparoscopic approach has grown adoption over the last decade. Recently, robotic operation was described as a new modality due to the ease for performing intracorporeal closure of the hernia defect. This study is one of the first multi-institutional case series evaluating robotic-assisted laparoscopic ventral hernia repairs, with the goal of describing robotic-assisted surgical techniques for ventral and incisional hernia repair and the outcomes in teaching and community hospital settings.

Methods

Medical records of consecutive patients (including surgeon's learning curve cases) who underwent ventral or incisional hernia repair utilizing the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA) were retrospectively reviewed. Data collected included preoperative history and perioperative outcomes.

Results

Data for a total of 368 patients from four institutions involving five surgeons were analyzed. They were predominantly females (60.3 %), and the mean age was 51 years. The majority of the patients were obese or morbidly obese (47.8 and 20.9 %), and 83.2 % of the patients had a history of prior abdominal operation. Conversion rate was 0.8 %, and mean length of stay was 1 day. Total postoperative complications rate up to 30 days was 8.4 %, of which incidence of paralytic ileus was 2.4 %.

Conclusion

This large case series of 368 patients demonstrates reproducibility of safety and performance associated with robotic-assisted ventral hernia repairs performed by five surgeons at four institutions. In addition, the results of short term perioperative outcomes for surgeons during their early experience for robotic-assisted cases are in the range of what is reported in the existing published data on laparoscopic and open ventral hernia repairs. Further comparative evidence initiatives are being pursued to determine the benefits of robotic-assisted technique and technology for long-term and patient-reported outcomes.

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Risk factors for lymph node metastasis and long-term outcomes of patients with early gastric cancer after non-curative endoscopic submucosal dissection

Abstract

Background

The long-term outcomes after non-curative gastric endoscopic submucosal dissection (ESD) are still unknown. We aimed to clarify the pathological risk factors for lymph node metastasis (LNM) of early gastric cancer (EGC) and the long-term outcomes among patients who were judged to have had non-curative ESD.

Methods

From September 2002 to December 2012, 506 patients who were judged to have had non-curative gastric ESD were enrolled and classified into two groups: (1) those who subsequently underwent additional surgical resection (surgical group, n = 323) and (2) those followed up without additional surgical resection (nonsurgical group, n = 183). We analyzed pathological risk factors for LNM of EGC in the surgical group. Additionally, we compared long-term outcomes in the two groups.

Results

LNM was found pathologically in 9.3 % of the surgical group (30/323) at the additional surgical resection after non-curative ESD. In the multivariate logistic regression analysis, lymphovascular invasion (LVI) was an independent risk factor for LNM in the surgical group (odds ratio 8.57, 95 % confidence interval 2.76–38.14, P < 0.0001). The 5-year cause-specific survival rate was similar in the surgical and nonsurgical groups (98.7 and 96.5 %, respectively; log-rank test, P = 0.07). In contrast, the 5-year cause-specific survival rate of patients with LVI in the surgical group was better than that in the nonsurgical group (98.2 and 79.1 %, respectively; log-rank test, P < 0.0001).

Conclusions

A detailed assessment of LVI is essential to the pathological evaluation of endoscopically resected specimens. An additional surgical resection should be strongly recommended for patients with LVI.

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Learning curves and surgical outcomes for proctored adoption of laparoscopic ventral mesh rectopexy: cumulative sum curve analysis

Abstract

Background

Laparoscopic ventral mesh rectopexy (VMR) is an effective and well-recognised treatment for symptoms of obstructive defecation in the context of rectal prolapse and recto-rectal intussusception. However, due to the technical complexity of VMR, a significant learning curve has been previously described. This paper examines the effect of proctored adoption of VMR on learning curves, operative times, and outcomes.

Methods

A retrospective database analysis of two district general hospitals was conducted, with inclusion of all cases performed by two surgeons since first adoption of the procedure in 2007–2015. Operative time, length of stay, and in-hospital complications were evaluated, with learning curves assessed using cumulative sum curves.

Results

Three hundred and eleven patients underwent VMR during the study period and were included for analysis. Patients were near-equally distributed between surgeons (surgeon A: n = 151, surgeon B, n = 160) with no significant differences between gender, age, or ASA grade. In-hospital morbidity was 3.2 %, with 0 % mortality. Cumulative sum curve analysis suggested a change point of between 25 and 30 cases based on operative times and length of stay and was similar between both surgeons. No significant change point was seen for morbidity or mortality.

Conclusion

VMR is an effective and safe treatment for rectal prolapse. Surgeons in this study were proctored during the adoption process by another surgeon experienced in VMR; this may contribute to increased safety and abbreviated learning curve. In the context of proctored adoption, this study estimates a learning curve of 25–30 cases, without detrimental impact on patient outcomes.

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A retrospective comparison of robotic cholecystectomy versus laparoscopic cholecystectomy: operative outcomes and cost analysis

Abstract

Introduction

Robotic-assisted surgery is gaining popularity in general surgery. Our objective was to evaluate and compare operative outcomes and total costs for robotic cholecystectomy (RC) and laparoscopic cholecystectomy (LC).

Methods and Procedures

A retrospective review was performed for all patients who underwent single-procedure RC and LC from January 2011 to July 2015 by a single surgeon at a large academic medical center. Demographics, diagnosis, perioperative variables, postoperative complications, 30-day readmissions, and operative and hospital costs were collected and analyzed between those patient groups.

Results

A total of 237 patients underwent RC or LC, and comprised the study population. Ninety-seven patients (40.9 %) underwent LC, and 140 patients (50.1 %) underwent RC. Patients who underwent RC had a higher body mass index (p = 0.03), lower rates of coronary artery disease (p < 0.01), and higher rates of chronic cholecystitis (p < 0.01). There were lower rates of intraoperative cholangiography (p < 0.01) and conversion to an open procedure (p < 0.01), however longer operative times (p < 0.01) for patients in the RC group. There were no bile duct injuries in either group, no difference in bile leak rates (p = 0.65), or need for reoperation (p = 1.000). Cost analysis of outpatient-only procedures, excluding cases with conversion to open or use of intraoperative cholangiography, demonstrated higher total charges (p < 0.01) and cost (p < 0.01) and lower revenue (p < 0.01) for RC compared to LC, with no difference in total payments (p = 0.34).

Conclusions

Robotic cholecystectomy appears to be safe although costlier in comparison with laparoscopic cholecystectomy. Further studies are needed to understand the long-term implications of robotic technology, the cost to the health care system, and its role in minimally invasive surgery.

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Robotic partial nephrectomy performed with Airseal versus a standard CO 2 pressure pneumoperitoneum insufflator: a prospective comparative study

Abstract

Background

Airseal represents a new generation of valveless and barrier-free surgical trocars that enable a stable pneumoperitoneum with continuous smoke evacuation and carbon dioxide (CO₂) recirculation during surgery. The aim of the current study was to evaluate the potential advantages of the Airseal compared to a standard CO₂ insufflator in the field of robotic partial nephrectomy (RPN).

Methods

Between October 2012 and April 2015, two cohorts of 122 consecutive patients with clinically localized renal cell carcinoma underwent RPN by a single surgeon, with the use of a standard CO₂ pressure insufflator (Group A, 55 patients) or Airseal (Group B, 67 patients) and were prospectively compared.

Results

The two groups were similar in baseline, preoperative characteristics. The mean dimension of the lesion, as evaluated by contrast-enhanced CT scan, was 30 (median 28; IQR 2) and 39 mm (median 40; IQR 2) for Groups A and B, respectively (p < 0.05). The complexity of the treated tumors was similar, as indicated by the mean RENAL nephrometry score. Positive surgical margins rate was similar in both groups (3.6 vs 4.5 %, p = 0.8) as well as the need for postoperative blood transfusion (9.1 vs 4.5 %, p = 0.3) and the development of postoperative acute kidney injury (16.4 vs 10.4 %, p = 0.3). Mean operative time and warm ischemia time were significantly shorter in Group B. Moreover, a significant increase in the cases performed as "zero ischemia" was observed in Group B (7.3 vs 30 %, p < 0.01).

Conclusions

This is the first study comparing the Airseal with a standard CO₂ insufflator system in the field of the RPN. The preliminary outcomes in terms of overall operative time, warm ischemia time and cases performed as "zero ischemia" are better with respect to standard insufflators. The feasibility, safety and efficacy of combining laser tumor enucleation with the valve-free insufflation systems should be evaluated.

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Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept

Abstract

Background

Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG).

Materials and methods

Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego^®, multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1).

Results

Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting.

Conclusions

Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

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A prospective randomized comparison of testicular functions, sexual functions and quality of life following laparoscopic totally extra-peritoneal (TEP) and trans-abdominal pre-peritoneal (TAPP) inguinal hernia repairs

Abstract

Background

There is very scant literature on the impact of inguinal hernia mesh repair on testicular functions and sexual functions following open and laparoscopic repair. The present randomized study compares TAPP and TEP repairs in terms of testicular functions, sexual functions, quality of life and chronic groin pain.

Methods

This study was conducted from April 2012 to October 2014. A total of 160 patients with uncomplicated groin hernia were randomized to either trans-abdominal pre-peritoneal (TAPP) repair or totally extra-peritoneal (TEP) repair. Testicular functions were assessed by measuring testicular volume, testicular hormone levels preoperatively and at 3 months postoperatively. Sexual functions were assessed using BMSFI, and quality of life was assessed using WHO-QOL BREF scale preoperatively and at 3 and 6 months postoperatively. Chronic groin pain was evaluated using the VAS scale at 3 months, 6 months and at 1 year.

Results

The median duration of follow-up was 13 months (range 6–18 months). The mean preoperative pain scores (p value 0.35) as well as the chronic groin pain were similar between TEP and TAPP repairs at 3 months (p value 0.06) and 6 months (p value 0.86). The testicular resistive index and testicular volume did not show any significant change at follow-up of 3 months (p value 0.9) in the study population. No significant difference was observed in testicular resistive index and testicular volume when comparing TEP and TAPP groups at at follow-up of 3 months (p value >0.05). There was a statistically significant improvement in the sexual drive score, erectile function and overall satisfaction over the follow-up period following laparoscopic inguinal hernia repair. However, sexual function improvement was similar in patients undergoing both TEP and TAPP repairs. All the domains of quality of life in the study population showed a significant improvement at a follow-up of 3 and 6 months. Subgroup analysis of all the domains of quality of life in both TAPP and TEP groups showed a similar increment as in the study population (p value <0.001); however, the mean scores of all the domains were comparable between the two subgroups (p value >0.05), preoperatively and 3 and 6 months follow-up.

Conclusions

Laparoscopic groin hernia repair improves the testicular functions, sexual functions and quality of life, but TEP and TAPP repairs are comparable in terms of these long-term outcomes.

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Intraoperative workload in robotic surgery assessed by wearable motion tracking sensors and questionnaires

Abstract

Background

The introduction of robotic technology has revolutionized radical prostatectomy surgery. However, the potential benefits of robotic techniques may have trade-offs in increased mental demand for the surgeon and the physical demand for the assisting surgeon. This study employed an innovative motion tracking tool along with validated workload questionnaire to assess the ergonomics and workload for both assisting and console surgeons intraoperatively.

Methods

Fifteen RARP cases were collected in this study. Cases were performed by 10 different participants, six primarily performed console tasks and four primarily performed assisting tasks. Participants had a median 12 (min—3, max—25) years of surgical experience. Both console and assisting surgeons performed robotic prostatectomy cases while wearing inertial measurement units (IMUs) that continuously track neck, shoulder, and torso motion without interfering with the sterile environment. Postoperatively, participants completed a workload questionnaire (SURG-TLX) and a body part discomfort questionnaire.

Results

Twenty-six questionnaires were completed from 13 assisting and 13 console surgeons over the 15 cases. Postoperative pain was reported highest for the right shoulder and neck. Mental demands were 41 % higher for surgeons at the console than assisting (p < 0.05), while physical demands were not significantly different. Assisting surgeons worked in demanding neck postures for 58 % of the procedure compared to 24 % for the console surgeon (p < 0.01). Surgeons at the console were primarily static and showed 2–5 times fewer movements than assisting surgeons (p < 0.01).

Conclusions

Postures were more ergonomic during console tasks than when assisting by the bedside; however, the console may constrain postures leading to static loads that have been associated with musculoskeletal symptoms for the neck, torso, and shoulders. The IMU sensors were effective at quantifying ergonomics in robotic prostatectomies, and these methods and findings have broad applications to other robotic procedures.

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Clinical impact of laparoscopic hepatectomy: technical and oncological viewpoints

Abstract

The objective of this study was to assess the clinical impact of laparoscopic hepatectomy from technical and oncological viewpoints through the consecutive 5-year experience of an expert team. The subjects consisted of 491 consecutive hepatectomies performed over the course of 5 years. A total of 190 hepatectomies (38.6 %) were performed laparoscopically, and the remaining 301 (61.4 %) were open hepatectomies. Chronological trends of operative procedures and their indications were evaluated, and patients with hepatocellular carcinoma (HCC) were analyzed from an oncological viewpoint. The proportion of laparoscopic hepatectomies performed increased significantly during the study period (from 17.6 to 49.5 %). According to chronological trends, right hepatectomy was standardized using consecutive steps after minor hepatectomy, left lateral sectionectomy, and left hepatectomy were standardized. The proportion of laparoscopic hepatectomies performed for HCC increased from 21.4 to 71.0 %. No significant difference was observed in the proportion of major hepatectomies performed for HCC between the open and laparoscopy groups (50.6 vs. 48.6 %, p = 0.8053), whereas that of anatomical segmentectomy for HCC was significantly lower in the laparoscopy group (28.7 vs. 11.1 %, p = 0.0064). All laparoscopic anatomical segmentectomies were of segments 5 and 6, and there was no segmentectomy of posterosuperior lesions. The present study shows the consecutive technical developmental processes for minor hepatectomy, left lateral sectionectomy, left hepatectomy, and right hepatectomy without compromising oncological principles. Laparoscopic anatomical segmentectomy for posterosuperior lesions may be the most technically demanding procedure, requiring individualized standardization.

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Efficacy of transoral incisionless fundoplication (TIF) for the treatment of GERD: a systematic review with meta-analysis

Abstract

Background

The efficacy of transoral incisionless fundoplication (TIF) performed with the EsophyX device (Redmond, Washington, USA) and its long-term outcomes in gastresophageal reflux disease (GERD) are debated. We, therefore, performed a systematic review with meta-analysis of studies evaluating the role of TIF in GERD.

Methods

A systematic search of EMBASE, SCOPUS, PubMed, and the Cochrane Library Central was performed. All original studies reporting outcomes in GERD patients who underwent TIF were identified. Only randomized controlled trials (RCTs) evaluating the efficacy of TIF, and prospective observational studies reporting outcomes after TIF were included.

Results

A total of 18 studies (963 patients) published between 2007 and 2015 were identified, including five RCTs and 13 prospective observational studies. The pooled relative risk of response rate to TIF versus PPIs/sham was 2.44 (95 % CI 1.25–4.79, p = 0.0009) in RCTs in the intention-to-treat analysis. The total number of refluxes was reduced after TIF compared with the PPIs/sham group. The esophageal acid exposure time and acid reflux episodes after TIF were not significantly improved. Proton-pump inhibitors (PPIs) usage increased with time and most of the patients resumed PPIs treatment at reduced dosage during the long-term follow-up. The total satisfaction rate after TIF was about 69.15 % in 6 months. The incidence of severe adverse events consisting of gastrointestinal perforation and bleeding was 2.4 %.

Conclusions

TIF is an alternative intervention in controlling GERD-related symptoms with comparable short-term patient satisfaction. Long-term results showed decreased efficacy with time. Patients often resume PPIs at reduced doses in the near future.

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Twenty-year experience with laparoscopic inguinal hernia repair in infants and children: considerations and results on 1833 hernia repairs

Abstract

Background

The role of laparoscopy in pediatric inguinal hernia (IH) is still controversial. The authors reported their twenty-year experience in laparoscopic IH repair in children.

Methods

In a twenty-year period (1995–2015), we operated 1300 infants and children (935 boys–365 girls) with IH using laparoscopy. The average age at surgery was 18 months (range 7 days–14 years). Body weight ranged between 1.9 and 50 kg (average 9.3). Preoperatively all patients presented a monolateral IH, right-sided in 781 cases (60.1 %) and left-sided in 519 (39.9 %). We excluded patients with bilateral IH and unstable patients in which laparoscopy was contraindicated. If the inguinal orifice diameter was ≥10 mm, we performed a modified purse string suture on peri-orificial peritoneum, in orifices ≤5 mm, we performed a N-shaped suture.

Results

No conversion to open surgery was reported. In 533 cases (41 %), we found a contralateral patency of internal inguinal ring that was always closed in laparoscopy. In 1273 cases (97.9 %), we found an oblique external hernia; in 21 cases (1.6 %), a direct hernia; and in 6 cases (0.5 %), a double hernia on the same side (hernia en pantaloon). We found an incarcerated hernia in 27 patients (2 %). Average operative time was 18 min (range 7–65). We recorded 5/1300 recurrences (0.3 %), but in the last 950 patients, we had no recurrence (0 %). We recorded 20 complications (1.5 %): 18 umbilical granulomas and two trocars scar infections, treated in outpatient setting.

Conclusions

On the basis of our twenty-year experience, we prefer to perform IH repair in children using laparoscopy rather than inguinal approach. Laparoscopy is as fast as inguinal approach, and it has the advantage to treat during the same anesthesia a contralateral patency occured in about 40 % of our cases and to treat also rare hernias in about 3 % of cases.

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Postoperative complications as an independent risk factor for recurrence after laparoscopic ventral hernia repair: a prospective study of 417 patients with long-term follow-up

Abstract

Background

Laparoscopic ventral hernia repair (LVHR) has become widely used. This study evaluates outcomes of LVHR, with particular reference to complications, seromas, and long-term recurrence.

Methods

A review of a prospective database of consecutive patients undergoing LVHR with intraperitoneal onlay mesh (IPOM) was performed at a single institution. Patient's characteristics, surgical procedures, and postoperative outcomes were analyzed and related to long-term recurrence.

Results

From 2005 to 2014, 417 patients underwent LVHR. Mean age and body mass index (BMI) were 54 years and 31 kg/m². Mesh fixation was carried out with transfascial sutures, completed with absorbable tacks (72 %), metal tacks (24 %), or intraperitoneal sutures (4 %). Intraoperative complications occurred in three patients. Overall morbidity included 8.25 % of minor complications and 2.5 % of major complications without mortality. The overall recurrence rate was 9.8 %. Median time for recurrence was 15.3 months (3–72) and median follow-up was 31.6 months (8–119). In a multivariate analysis, previous interventions (OR 1.44; CI 1.15–1.79; p = 0.01), postoperative complications (OR 2.57; CI 1.09–6.03; p = 0.03), and Clavien–Dindo score >2 (OR 1.43; CI 1.031–1.876; p = 0.02) appeared as independent prognostic factors of recurrence. Minor complications were associated with 14.7 % of recurrence and major complications with 30 % of recurrence. Emergency LVHR (6 %) did not increase the rate of complications. Overall seroma rate was 18.7 %, with 1.4 % of persisting or complicated seroma. BMI (OR 1.05; CI 1.01–1.08; p = 0.026) and vascular surgery history (OR 5.74; CI 2.11–15.58; p < 0.001) were independent predictive factors for seroma. Recurrence did not appear to be related to seroma.

Conclusion

LVHR combines the benefits of laparoscopy with those of mesh repair. Seroma formation should no longer be considered as a complication. It is spontaneously regressive in most cases. Postoperative complications and their degree of severity appear to be independent prognostic factors for recurrence, which can be limited with a standardized technique and may make IPOM–LVHR a reference procedure.

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Esophageal stent fixation with endoscopic suturing device improves clinical outcomes and reduces complications in patients with locally advanced esophageal cancer prior to neoadjuvant therapy: a large multicenter experience

Abstract

Background

Endoscopic placement of fully covered self-expanding metal stents (FCSEMS) to treat malignant dysphagia in patients with esophageal cancer significantly improves dysphagia; however, these stents have a high migration rate.

Aim

To determine whether FCSEMS fixation using an endoscopic suturing device treated malignant dysphagia and prevented stent migration in patients with locally advanced esophageal cancer receiving neoadjuvant therapy when compared to patients with FCSEMS placement alone.

Method

A review of patients with locally advanced esophageal cancer who underwent FCSEMS placement at 3 centers was performed. Patients were divided into two groups: Group A (n = 26) was composed of patients who underwent FCSEMS placement with suture placement, and Group B (n = 67) was composed of patients with FCSEMS placement alone.

Results

There were no significant differences between Groups A and B in demographics, and tumor characteristics. The technical success rate for stent placement was 100 %. There was no difference between Groups A and B in the median stent diameter and stent lengths. Mean dysphagia score obtained at 1 week after stent placement had improved significantly from baseline (2.4 and 1, respectively, p < 0.001). Patients had a median follow-up of 4 months. Immediate adverse events were mild chest discomfort in 4 patients in Group A and 2 patients in Group B (p = 0.05), and significant acid reflux in 3 patient in Group A compared to 2 patients in Group B (p = 0.1). The stent migration rate was significantly lower in Group A compared to compared to Group B (7.7 vs 26.9 %, respectively, p = 0.004). There was a delayed perforation in 1 patient and 1 death due to aspiration pneumonia in Group B.

Conclusion

Fixation of esophageal FCSEMSs by using an endoscopic suturing device in patients receiving neoadjuvant therapy was shown to be feasible, safe, and relatively effective at preventing stent migration compared to those who had stent placed alone.

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