Autonomous Motility of Polymer Films

Abstract

Adaptive soft materials exhibit a diverse set of behaviors including reconfiguration, actuation, and locomotion. These responses however, are typically optimized in isolation. Here, the interrelation between these behaviors is established through a state space framework, using Nylon 6 thin films in a humidity gradient as an experimental testbed. It is determined that the dynamic behaviors are a result of not only a response to but also an interaction with the applied stimulus, which can be tuned via control of the environment and film characteristics, including size, permeability, and coefficient of hygroscopic expansion to target a desired behavior such as multimodal locomotion. Using these insights, it is demonstrated that films simultaneously harvest energy and information from the environment to autonomously move down a stimulus gradient. Improved understanding of the coupling between an adaptive material and its environment aids the development of materials that integrate closed loop autonomous sensing, actuation, and locomotion.

Autonomous multimodal locomotion, oscillation, and reconfiguration are demonstrated in commodity polymer films. A behavioral state space is developed that connects these behaviors to the common underlying mechanism. Films are shown to harvest not only energy but also information from their environment, resulting in directed locomotion down a humidity gradient.

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Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans

Abstract

African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that cutaneous hyperemic response to local heating is reduced in young AA relative to CA and this is due to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibers received (1) lactated Ringer's (Control), (2) 10 mm Ascorbic Acid, or (3) 10 μm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) at a rate of 2.0 μl min⁻¹. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux/mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23 ± 4 yrs) subjects participated. During 39°C heating %CVCmax was lower in AA at Control (CA: 65 ± 20 % vs. AA: 47 ± 15 %; P < 0.05) and Ascorbic Acid (CA: 73 ± 14 % vs. AA: 49 ± 17 %; P < 0.01). At Tempol site, there were no differences between groups. This was followed by infusion of 10 mm Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) at all sites to assess nitric oxide (NO) contribution to vasodilation during local heating. The NO contribution was lower in AA relative to CA at 39°C; however, this was restored with Tempol. These data suggest that: (1) cutaneous vasodilation to local heating is blunted in AA relative to CA. (2) elevated O₂⁻ generation attenuates NO-mediated cutaneous vasodilation in AA.

This article is protected by copyright. All rights reserved

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Myeloid neoplasms with t(12;22)(p13;q12)/MN1-EVT6: a systematic review of 12 cases

Abstract

t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2). There were five men and seven women with a median age of 43 years (range, 15–63 years) at initial diagnosis. Cytogenetics revealed t(12;22) as the sole abnormality in five patients, with the remaining seven patients harboring additional chromosomal aberrations. Of the five patients who received known therapy regimens, all of them had poor response to the idarubicin/mitoxantrone + cytarabine regimen. Of the seven patients with follow-up information, six patients died with a median overall survival time of only 5 months (range, 1–12 months) after the emergence of t(12;22). In summary, patients with t(12;22) are frequently associated with myeloid neoplasms, poor response to chemotherapy, and inferior outcome.

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HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease

Summary

Background

Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis.

Aim

To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles.

Methods

A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype.

Results

The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients.

Conclusions

The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD.

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Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor

Summary

Background

The combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low- to middle-income countries in the future.

Aim

To identify key predictors of response that can be used to tailor treatment decisions.

Methods

A cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV.

Results

The overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low-level viraemia at the end of treatment. The model-based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance-associated substitutions [position 28 (OR = 70.3, P<.001) and/or 31 (OR = 61.6, P = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on-treatment viral kinetics.

Conclusion

This real-world study confirms the excellent results of clinical trials with therapies based on a combination of SOF plus an NS5A inhibitor. It suggests that a personalized approach including baseline NS5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients.

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Bone microarchitecture and bone mineral density in multiple sclerosis

Background

Multiple sclerosis (MS) patients are at increased risk of reduced bone mineral density (BMD) and fractures. The aetiology of bone loss in MS is unclear. Trabecular bone score (TBS) is a novel analytical tool that provides a measurement of the bone microarchitecture. Decreased TBS predicts increased fracture risk independently of BMD. To date, no studies have investigated TBS in MS patients.

Objectives

To assess bone quality in MS patients by TBS and to evaluate potential risk factors that may affect BMD and TBS in patients with MS.

Methods

Two hundred sixty MS patients were included. TBS was calculated using TBS iNsight software (MediMaps^®). Multivariable regression analyses were performed with information on smoking, alcohol, glucocorticoid (GC) treatment, sun exposure, physical activity, vitamin D and BMI.

Results

Trabecular bone score was not significantly different from an age-matched reference population. Low TBS was associated with high age (P = .014) and smoking (P = .03). Smoking and physical inactivity were associated with low BMD in spine (P = .034, P = .032). GC treatment was not associated with TBS.

Conclusion

We could not find altered TBS values among MS patients, suggesting that BMD alone, and not the bone microarchitecture, is affected in MS. However, larger studies are needed to verify these findings and to establish the role of TBS in MS. As in the background population, physical activity and non-smoking habits are associated with better bone health in MS.

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Biochemical characterization of a fibrinolytic enzyme composed of multiple fragments

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Ectopic expression of BdCIPK31 confers enhanced low-temperature tolerance in transgenic tobacco plants

Abstract

Calcineurin B-like protein (CBL), the Ca²⁺ sensor, and its interacting protein kinases (CIPKs) play essential roles in plants' response to stress. However, few studies have focused on the functions of CIPKs in low-temperature response. In the present study, BdCIPK31, a cold-responsive CIPK in Brachypodium distachyon, was found to participate in low-temperature response. Ectopic expression of BdCIPK31 conferred cold tolerance in transgenic tobaccos. Further analyses indicated that expression of BdCIPK31 improved ROS detoxication and omsoprotectant biosynthesis in transgenic plants under low-temperature treatment, suggesting that the BdCIPK31 functions positively in plant adaption to the cold-induced oxidative and osmotic stresses. Moreover, BdCIPK31 could upregulate the expressions of some representative stress-related genes under cold stress. In conclusion, these findings suggest that BdCIPK31 functions positively in plant cold response.

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Tumor side as model of integrative molecular classification of colorectal cancer

It has long since been recognized that colorectal cancer is molecularly heterogeneous and its clinical behavior differs if primary tumor was located in the right or left side of the colon. Recent studies have shown that part of this heterogeneity is captured by the anatomical location of the tumor.

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Alteration of the tumor stroma using a consensus DNA vaccine targeting Fibroblast Activation Protein (FAP) synergizes with anti-tumor vaccine therapy in mice

Purpose: Fibroblast activation protein (FAP) is over-expressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to impact the tumor stroma. Our aim was to extend this earlier work through development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and anti-tumor activity of this novel FAP vaccine in pre-clinical studies, and correlated these findings to patient data. Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8+ and CD4+ immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared to a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor-antigen specific DNA vaccines to enhance anti-tumor immunity. Evaluation of the tumor microenvironment showed increased CD8+ T cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from the Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8+ T cell infiltration. Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a micro-consensus FAP vaccine provides a two fisted punch inducing responses that target both the tumor microenvironment and tumor cells directly.

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Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?

Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the number of trials in mid to late-stage with integrated biomarkers. Additionally, blood based biomarkers that provide a measure of disease activity and allow for minimally invasive tumor analyses are emerging, including circulating tumor DNA, exosomes and circulating tumor cells. In this article, we will review potential biomarkers for currently approved therapies as well as emerging biomarkers for therapeutics under development.

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R-2HG Targets FTO to Increase m6A Levels and Suppress Tumor Growth [Research Watch]

R-2HG, thought to be an oncometabolite in IDH-mutant tumors, has antitumor activity in leukemia and glioma.

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mTORC2-Driven Lipid Synthesis Promotes Liver Tumorigenesis [Research Watch]

mTORC2-induced lipid metabolism promotes hepatosteatosis progression to hepatocellular carcinoma.

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Targeting JAG1 Sensitizes Bone Metastases to Chemotherapy [Research Watch]

Chemotherapy induces JAG1 expression in osteoblasts, promoting chemoresistance in bone metastases.

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PEGPH20 May Improve Standard-of-Care Therapy in Pancreatic Cancer [Research Watch]

The HA-degrading drug PEGPH20 plus standard therapy extends survival in metastatic pancreatic cancer.

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Child Road Traffic Injury Mortality in Victoria, Australia (0-14 years), the need for targeted action

Publication date: Available online 21 December 2017
Source:Injury
Author(s): S.S.M Chang, R.C.A Symons, J. Ozanne-Smith
IntroductionExtensive efforts to reduce unintentional injury were enacted in the last three decades of the 20th century. Examination of road traffic injury mortality indicates the extent of fatal, unintentional child injuries (0-14 years) future interventions must address.Aims(1) describe in-depth child road traffic injury (RTI) deaths 2001-2012 in Victoria, Australia (2) identify the potential preventability of the RTI causes by currently available countermeasures and scope for enhanced implementation and novel solutions.MethodFatal Victorian child injury data were extracted from the National Coronial Information System (NCIS) for the 12 year period January 2001-December 2012. All on-road data was analysed. Data for passenger and pedestrian deaths was examined in depth. Associated factors were determined using univariate and pairwise analysis of factors. Published WHO key prevention strategies, and the recent literature were reviewed, focusing on the identified fatalities among children 0-14 years.ResultsFor 172 RTI deaths, head injury was the leading medical cause of death (68%). Significantly, the most vulnerable age group for both passengers and pedestrians was 0-4 years. Rural children were over-represented with children aged 0-4 years at greatest risk. Common factors for occupants were loss of control and veering to the incorrect side. For pedestrians the major factors related to rural residence and supervision.Discussionand Conclusions This study confirms that RTIs are complex and follow chains of events. Numerous promising interventions were identified. Wider implementation of these advanced engineering, education and enforcement strategies may further improve mortality rates in Victoria. Feasible solutions for aspects of the child pedestrian problem remain elusive. This study describes the RTI problem in greater depth than previous studies and reveals that some existing measures are not fully implemented. The need for targeted action in: 0–4 year olds; head injury; and rural regions of Victoria is highlighted. The need for a safe systems approach is paramount.



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Metabolic Profile of Ex Vivo Lung Perfusate Yields Biomarkers for Lung Transplant Outcomes

Objective: To identify potential biomarkers during ex vivo lung perfusion (EVLP) using metabolomics approach. Summary Background Data: EVLP increases the number of usable donor lungs for lung transplantation (LTx) by physiologic assessment of explanted marginal lungs. The underlying paradigm of EVLP is the normothermic perfusion of cadaveric lungs previously flushed and stored in hypothermic preservation fluid, which allows the resumption of active cellular metabolism and respiratory function. Metabolomics of EVLP perfusate may identify metabolic profiles of donor lungs associated with early LTx outcomes. Methods: EVLP perfusate taken at 1and 4 hperfusion were collected from 50 clinical EVLP cases, and submitted to untargeted metabolic profiling with mass spectrometry. The findings were correlated with early LTx outcomes. Results: Following EVLP, 7 cases were declined for LTx. In the remaining transplanted cases, 9 cases developed primary graft dysfunction (PGD) 3. For the metabolic profile at EVLP-1h, a logistic regression model based on palmitoyl-sphingomyelin, 5-aminovalerate, and decanoylcarnitine yielded a receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.987 in differentiating PGD 3 from Non-PGD 3 outcomes. For the metabolic profile at EVLP-4h, a logistic regression model based on N2-methylguanosine, 5-aminovalerate, oleamide, and decanoylcarnitine yielded a ROC curve with AUC 0.985 in differentiating PGD 3 from non-PGD 3 outcomes. Conclusions: Metabolomics of EVLP perfusate revealed a small panel of metabolites highly correlated with early LTx outcomes, and may be potential biomarkers that can improve selection of marginal lungs on EVLP. Further validation studies are needed to confirm these findings.

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Duration of Antimicrobial Prophylaxis in Patients Undergoing Major Hepatectomy With Extrahepatic Bile Duct Resection: A Randomized Controlled Trial

Objective: To evaluate the optimal duration of antimicrobial prophylaxis in patients undergoing "complicated"' major hepatectomy with extrahepatic bile duct resection. Background: To date, 4 randomized controlled trials (RCTs) have assessed the duration of antimicrobial prophylaxis after hepatectomy. However, all of these previous studies involved only "simple" hepatectomy without extrahepatic bile duct resection. Methods: Patients with suspected hilar obstruction scheduled to undergo complicated hepatectomy after biliary drainage were randomized to 2-day (antibiotic treatment on days 1 and 2) or 4-day (on days 1 to 4) groups. Antibiotics were selected based on preoperative bile culture. The primary endpoint was the incidence of postoperative infectious complications. Results: In total, 86 patients were included (43 patients in each arm) without between-group differences in baseline characteristics. Bile culture positivity was similar between the 2 groups. No significant between-group differences were observed in surgical variables. The incidence of any infectious complications was similar between the 2 groups (30.2% in the 2-day group and 32.6% in the 4-day group). The positive rate of systemic inflammatory response syndrome and the incidence of additional antibiotic use were almost identical between the 2 groups. According to Clavien-Dindo classification, grade 3a or higher complications occurred in 23 patients (53.5%) in the 2-day group and 29 patients (67.4%) in the 4-day group (P = 0.186). Postoperative hospital stay was not different between the 2 groups. Conclusions: Two-day administration of antimicrobial prophylaxis is sufficient for patients undergoing hepatectomy with extrahepatic bile duct resection [Registration number: ID 000009800 (University Hospital Medical Information Network, http://www.umin.ac.jp)].

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To Bleed or Not to Bleed: Is That the Question?

No abstract available

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Laparoscopic Liver, Pancreas, and Biliary Surgery

No abstract available

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Carolinas Comfort Scale as a Measure of Hernia Repair Quality of Life: A Reappraisal Utilizing 3788 International Patients

Objective: The goal of the present study was to reaffirm the psychometric properties of the CCS using an expansive, multinational cohort. Background: The Carolinas Comfort Scale (CCS) is a validated, disease-specific, quality of life (QOL) questionnaire developed for patients undergoing hernia repair. Methods: The data were obtained from the International Hernia Mesh Registry, an American, European, and Australian prospective, hernia repair database designed to capture information delineating patient demographics, surgical findings, and QOL using the CCS at 1, 6, 12, and 24 months postoperatively. Results: A total of 3788 patients performed 11,060 postoperative surveys. Patient response rates exceeded 80% at 1 year postoperatively. Acceptability was demonstrated by an average of less than 2 missing items per survey. The formal test of reliability revealed a global Cronbach's alpha exceeding 0.95 for all hernia types. Test-retest validity was supported by the correlation found between 2 different administrations of the CCS using the kappa coefficient. Principal component analysis identified 2 components with a good distribution of variance, with the first component explaining approximately 60% of the variance, regardless of hernia type. Discriminant validity was assessed by comparing survey responses and use of pain medication at 1 month postoperatively and analysis revealed that symptomatic patients demonstrated significantly higher odds of requiring pain medication in all activity domains and for all hernia types. Conclusions: The present study confirms that the CCS questionnaire is a validated, sensitive, and robust instrument for assessing QOL after hernia repair, which has become a predominant outcome measure in this discipline of surgery.

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Comparative Performance of the Complexity Classification and the Conventional Major/Minor Classification for Predicting the Difficulty of Liver Resection for Hepatocellular Carcinoma

Objective: To compare performances for predicting surgical difficulty and postoperative complications. Background: An expert panel recently proposed a complexity classification for liver resection with 3 categories of complexity (low, medium, or high). We compared this new classification with the conventional major/minor classification. Methods: We retrospectively reviewed 469 hepatocellular carcinoma patients who underwent liver resection between 1 January 1, 2004 and June 30, 2015. We used receiver-operating characteristic curve analysis to compare the performances of both classifications for predicting perioperative outcomes. Results: Both classifications effectively differentiated subgroups of patients in terms of their intraoperative findings and short-term outcomes, including blood loss, transfusion rate, operation time, and postoperative hospital stay (all P

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Commentary of “Why do General Surgeons Decide to Retire?”

No abstract available

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Evaluation of New Classifications for Liver Surgery: Can Anatomic Granularity Predict Both Complexity and Outcomes of Hepatic Resection?

No abstract available

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Prevalence and Risk Factors for Bariatric Surgery Readmissions: Findings From 130,007 Admissions in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program

Objective: To evaluate readmissions following laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), and laparoscopic Roux-en-Y gastric bypass (LRYGB). Background: Few studies have evaluated national readmission rates for primary bariatric surgery with national, bariatric-specific data. Methods: Patients undergoing primary LAGB, LSG, or LRYGB from January 1, 2014 to December 31, 2014, at 698 centers were identified based upon Current Procedural Terminology codes. The primary outcome was 30-day readmission from date of initial operation. Results: A total of 130,007 patients who underwent primary bariatric surgery were identified: 7378 LAGB (5.7%), 80,646 LSG (62.0%), and 41,983 LRYGB (32.3%). A total of 5663 (4.4%) patients were readmitted within 30 days for all causes. Patients undergoing LAGB had the lowest related readmission rate of 1.4%, followed by LSG (2.8%), and LRYGB (4.9%). Of patients who had a complication, 17.9% (n = 785) were readmitted, whereas those without readmission had a complication 1.9% of the time (P

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Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas: A Report from The Pancreatic Surgery Consortium

Objective: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. Summary Background Data: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. Methods: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. Results: We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P 3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. Conclusions: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

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Volume Increases and Shared Decision-making in Joint Replacement Bundles

No abstract available

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Photochemical Tissue Passivation Attenuates AV Fistula Intimal Hyperplasia

Objective: We hypothesized that decreasing vein compliance would protect the vein against stretch injury and reduce intimal hyperplasia (IH). Background: Although arteriovenous fistulas (AVFs) are the criterion standard for vascular access, their effectiveness is limited by poor patency with 40% to 60% failing due to IH. Venous stretch injury from exposure to arterial pressure induces IH. Photochemical tissue passivation (PTP) crosslinks adventitial collagen, decreasing vein compliance to resemble that of an artery. Methods: AVFs were created between the femoral artery and epigastric vein in rats (n = 29). PTP was performed on the vein immediately before vessel anastomosis. AVFs were harvested after four weeks. Venous diameter was measured at the initial procedure and harvest. Intimal area was measured for each segment. Ultrasound was performed at harvest to measure AVF flow. Results: Following AVF construction, venous diameter increased by 10% ± 18% for PTP-treated vessels and 78% ± 27% for controls (P ≤ 0.0001). At one month, PTP reduced AVF dilation by 71% compared to control (69% ± 29% vs 241% ± 78%; P ≤ 0.0001). Both juxta-anastomotic intimal area and total intimal area were reduced in PTP-treated vessels compared to control vessels. Specifically, intimal area was 0.024 ± 0.018 and 0.095 ± 0.089 mm2 for PTP-treated juxta-anastomotic segments of AVF and control, respectively (P

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Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung Cancer Surgery

No abstract available

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Inside Baseball-leveling the Playing Field in the Surgical Residency Selection Process

No abstract available

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Design Principles for Building a Leadership Development Program in a Department of Surgery

No abstract available

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Commentary on Brief Clinical Report: Reconstruction/Repair of Iatrogenic Biliary Injuries Is the Robot Offering a New Option?

No abstract available

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Watchful Waiting Versus Surgery of Mildly Symptomatic or Asymptomatic Inguinal Hernia in Men Aged 50 Years and Older: A Randomized Controlled Trial

Objective: To compare if watchful waiting is noninferior to elective repair in men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia. Background: The role of watchful waiting in older male patients with mildly symptomatic or asymptomatic inguinal hernia is still not well-established. Methods: In this noninferiority trial, we randomly assigned men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia to either elective inguinal hernia repair or watchful waiting. Primary endpoint was the mean difference in a 4-point pain/discomfort score at 24 months of follow-up. Using a 0.20-point difference as a clinically relevant margin, it was hypothesized that watchful waiting was noninferior to elective repair. Secondary endpoints included quality of life, event-free survival, and crossover rates. Results: Between January 2006 and August 2012, 528 patients were enrolled, of whom 496 met the inclusion criteria: 234 were assigned to elective repair and 262 to watchful waiting. The mean pain/discomfort score at 24 months was 0.35 [95% confidence interval (CI) 0.28–0.41)] in the elective repair group and 0.58 (95% CI 0.52–0.64) in the watchful waiting group. The difference of these means (MD) was −0.23 (95% CI −0.32 to −0.14). In the watchful waiting group, 93 patients (35·4%) eventually underwent elective surgery and 6 patients (2·3%) received emergent surgery for strangulation/incarceration. Postoperative complication rates and recurrence rates in these 99 operated individuals were comparable with individuals originally assigned to the elective repair group (8.1% vs 15.0%; P = 0.106, 7.1% vs 8.9%; P = 0.668, respectively). Conclusions: Our data could not rule out a relevant difference in favor of elective repair with regard to the primary endpoint. Nevertheless, in view of all other findings, we feel that our results justify watchful waiting as a reasonable alternative compared with surgery in men aged 50 years and older.

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A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery

Objective: The aim of this study was to determine the bleeding risks associated with single (aspirin) and dual (aspirin + clopidogrel) antiplatelet therapy (DAPT) versus placebo or no treatment in adults undergoing noncardiac surgery. Summary of Background Data: The impact of antiplatelet therapy on bleeding during noncardiac surgery remains controversial. A meta-analysis was performed to examine the risk associated with single and DAPT. Methods: A systematic review of antiplatelet therapy, noncardiac surgery, and perioperative bleeding was performed. Peer-reviewed sources and meeting abstracts from relevant societies were queried. Studies without a control group, or those that only examined patients with coronary stents, were excluded. Primary endpoints were transfusion and reintervention for bleeding. Results: Of 11,592 references, 46 studies met inclusion criteria. In a meta-analysis of >30,000 patients, the relative risk (RR) of transfusion versus control was 1.14 [95% confidence interval (CI) 1.03–1.26, P = 0.009] for aspirin, and 1.33 (1.15–1.55, P = 0.001) for DAPT. Clopidogrel had an elevated risk, but data were too heterogeneous to analyze. The RR of bleeding requiring reintervention was not significantly higher for any agent compared to control [RR 0.96 (0.76–1.22, P = 0.76) for aspirin, 1.84 (0.87–3.87, P = 0.11) for clopidogrel, and 1.51 (0.92–2.49, P = 0.1) for DAPT]. Subanalysis of thoracic and abdominal procedures was similar. There was no difference in RR for myocardial infarction [1.06 (0.79–1.43)], stroke [0.97 (0.71–1.33)], or mortality [0.97 (0.87–1.1)]. Conclusions: Antiplatelet therapy at the time of noncardiac surgery confers minimal bleeding risk with no difference in thrombotic complications. In many cases, it is safe to continue antiplatelet therapy in patients with important indications for their use.

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Get SET: aligning anatomy demonstrator programmes with Surgical Education and Training selection criteria

Background

Prevocational doctors aspiring to surgical careers are commonly recruited as anatomy demonstrators for undergraduate and graduate medical programmes. Entry into Surgical Education and Training (SET) is highly competitive and a unique opportunity exists to align anatomy demonstrator programmes with the selection criteria and core competencies of SET programmes. This study used a qualitative approach to (i) determine what criteria applicants for SET are assessed on and (ii) identify criteria that could be aligned with and enhanced by an anatomy demonstrator programme.

Methods

The selection guidelines of all nine surgical specialties for the 2017 intake of SET trainees were analysed using qualitative content analysis methodology.

Results

The Royal Australasian College of Surgeons adopted a holistic approach to trainee selection that assessed both discipline-specific and discipline-independent skills. Qualitative content analysis identified eight categories of key selection criteria: medical expertise, scholarly activity, professional identity, interpersonal skills, integrity, self-management, insight and self-awareness and community involvement. The structured curriculum vitae was heavily weighted towards discipline-specific skills, such as medical expertise and scholarly activity. Insufficient information was available to determine the weighting of selection criteria assessed by the structured referee reports or interviews.

Conclusion

Anatomy demonstrator programmes provide prevocational doctors with unique opportunities to develop surgical skills and competencies in a non-clinical setting. Constructively aligned anatomy demonstrator programmes may be particularly beneficial for prevocational doctors seeking to improve their anatomical knowledge, teaching skills or scholarly activity.

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In defence of sympathy, in consideration of empathy, and in praise of compassion: A history of the present

"History is the best medicine for a sick mind, for in history you have a record of the infinite variety of human experience plainly set out for all to see, and in that record you can find for yourself and your country both examples and warnings: fine things to take as models, base things rotten through and through to avoid"Livy, Roman Historian

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The Supply of Prescription Opioids: Contributions of Episodic-Care Prescribers and High-Quantity Prescribers

We determine episodic and high-quantity prescribers' contribution to opioid prescriptions and total morphine milligram equivalents in California, especially among individuals prescribed large amounts of opioids.

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ECG Predictors of Cardiac Arrhythmias in Older Adults With Syncope

Cardiac arrhythmia is a life-threatening condition in older adults who present to the emergency department (ED) with syncope. Previous work suggests the initial ED ECG can predict arrhythmia risk; however, specific ECG predictors have been variably specified. Our objective is to identify specific ECG abnormalities predictive of 30-day serious cardiac arrhythmias in older adults presenting to the ED with syncope.

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External quality assessment of malaria microscopy diagnosis among public health facilities in West Amhara Region, Ethiopia

To evaluate the importance of external quality assessment program on malaria microscopic diagnosis.

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Associations of Genetic Variations in the Seed Regions of MicroRNAs with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy

MicroRNAs play a key role in posttranscriptional regulation of mRNA and multiple cellular biological processes. We analyzed 18 SNPs in microRNA seed regions and identified two SNPs associated with acute adverse events and survival time in patients with rectal cancer receiving CAP-based chemoradiotherapy. These SNPs might serve as independent biomarkers for predicting acute adverse events and prognosis in patients with rectal cancer. Independent replication studies are required to confirm these results.

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Hippocampal sparing during Craniospinal irradiation, what did we learn about the incidence of peri hippocampus metastases?

Whole brain irradiation (WBI) plays a role in neurocognitive effects.New technologies make WBI possible while sparing the hippocampal region (HA-WBI).As already done in adult population with primary carcinoma, to safety propose HA-WBI, our study aimed to assess the distribution of brain metastases within the peri hippocampal area (PHA) in high-risk medulloblastoma children.In conclusion, we recommend to evaluate HA-WBI strategy for subgroup of high risk patients without metastatic disease

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Radiotherapy for Aggressive Fibromatosis: The Association Between Local Control and Age

Radiotherapy is used in the treatment of unresectable or recurrent aggressive fibromatosis; prior data suggests that local control may be diminished in younger patients. We analyzed a single-institution experience of patients treated with radiotherapy for aggressive fibromatosis over 4 decades. Patients 20 years or under at diagnosis experience diminished local control following radiotherapy compared with patients over 40 years old at diagnosis, suggesting possible biologic differences between tumors in these age groups.

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Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain

The efficacy of a HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis was investigated in an intracranial mouse model. Mice were irradiated with the Leksell GammaKnife® PerfexionTM, and the development and progression of radiation necrosis were monitored longitudinally in vivo using magnetic resonance imaging, supported with correlative histology. Both topotecan and AMD3100 can, independently, mitigate the development of RN in mouse brain by reducing inflammation.

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Risk Factors for Malignant Transformation of Low Grade Glioma

The incidence, risk factors, and outcomes of LGG patients who undergo malignant transformation in the era of temozolomide are not well known. This study evaluates these factors from a large group of WHO Grade II glioma patients treated at our tertiary care institution. We found that older age, male sex, multiple tumor locations, chemotherapy alone, and extent of resection were significant predictors of malignant transformation.

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Outcomes of Patients with Primary Sacral Chordoma Treated with Definitive Proton Beam Therapy

We conducted a retrospective analysis to evaluate the safety and efficacy of definitive proton beam therapy with 70.4 Gy (relative biological effectiveness) in 32 fractions for primary sacral chordoma. This cohort study of 33 eligible patients shows that this treatment modality is safe and effective, and has the potential to reduce pain.

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Proceedings of the National Cancer Institute Workshop on Charged Particle Radiobiology

In April 2016, the National Cancer Institute (NCI) hosted a multidisciplinary workshop to discuss current knowledge of the radiobiological aspects of charged particles used in cancer therapy, to identify gaps in that knowledge that may hinder the effective clinical use of charged particles and to propose research that may help fill those gaps. The workshop was organized into ten topics ranging from biophysical models to clinical trials and included treatment optimization, relative biological effectiveness (RBE) of tumors and normal tissues, hypofractionation with particles, combination with immunotherapy, omics, hypoxia and particle-induced second malignancies.

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Association between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas

Patients with soft tissue sarcomas, a group of rare malignancies that require complex management, may benefit from care at high-volume treatment facilities as such facilities may offer greater physician expertise, superior resource availability, and delivery of highly coordinated care. Using the National Cancer Database, we demonstrate an association between high facility case volume and overall survival in patients with soft tissue sarcomas; these findings support centralization of care for sarcomas.

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Adaptive boost target definition in high-risk head and neck cancer based on multi-imaging risk biomarkers

Several imaging risk biomarkers for treatment failure in head and neck cancer have been identified, largely in isolation. Understanding the spatial association between these imaging risk biomarkers is lacking, which could impact on decision making in clinical trials. This study found that high FDG uptake, low blood volume and low diffusion coefficient in head-and neck cancer identifies large distinct tumor subvolumes. Boosting target defined on a single imaging modality may not be adequate to achieve sufficient clinical benefits.

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External Beam Radiotherapy and Brachytherapy for Cervical Cancer: The experience of The National Centre for Radiotherapy in Accra, Ghana

Most women with cervical cancer in Sub-Saharan Africa present with advanced disease. These women require treatment with concurrent chemo-radiotherapy and brachytherapy, but there is a scarcity of data on patient outcomes. We retrospectively reviewed the experience of The XXXX XXXX for XXXX and I in XXXXX, Ghana. We report encouraging results, demonstrating what can be achieved with a well-established cancer program in Sub-Saharan Africa.

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Endotracheal Tube Connector: Holding Breaths!

No abstract available

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Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain

BACKGROUND: Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. METHODS: To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. RESULTS: The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% CI, 33.3–53.9) in the trigeminal ganglia than in the spinal one. CONCLUSIONS: The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain. Accepted for publication October 23, 2017. Funding: This study was supported by the Ministry of Science and Innovation of Spain (SAF2012-40075-C02-01) and General Directorate for Scientific Research of Community of Madrid (S-2011/BMD-2308). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eva María Sánchez-Robles, PhD, Facultad Ciencias de la Salud, Área de Farmacología y Nutrición, Universidad Rey Juan Carlos, Avda Atenas, s/n. 28922 Alcorcón, Madrid, Spain. Address e-mail to eva.sanchez@urjc.es. © 2017 International Anesthesia Research Society

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The Effect of High-Frequency, Structured Expert Feedback on the Learning Curves of Basic Interventional Ultrasound Skills Applied to Regional Anesthesia

BACKGROUND: Proficiency in needle-to-ultrasound beam alignment and accurate approach to structures are pivotal for ultrasound-guided regional anesthesia. This study evaluated the effects of high-frequency, structured expert feedback on simulation training of such abilities. METHODS: Forty-two subjects randomly allocated as controls or intervention participated in two 25-trial experiments. Experiment 1 consisted of inserting a needle into a bovine muscular phantom parallel to the ultrasound beam while maintaining full imaging of the needle. In experiment 2, the needle aimed to contact a target inside the phantom. Intervention subjects received structured feedback between trials. Controls received a global critique after completing the trials. The slopes of the learning curves derived from the sequences of successes and failures were compared. Change-point analyses identified the start and the end of learning in trial sequences. The number of trials associated with learning, the number of technical errors, and the duration of training sessions were compared between intervention and controls. RESULTS: In experiment 1, learning curves departed from 73% (controls) and 76% (intervention) success rates; slopes (standard error) were 0.79% (0.02%) and 0.71% (0.04), respectively, with mean absolute difference of 0.18% (95% confidence interval [CI], 0.17%–0.19%; P = 0). Intervention subjects' learning curves were shorter and steeper than those of controls. In experiment 2, the learning curves departed from 43% (controls) and 80% (intervention) success rates; slopes (standard error) were 1.06% (0.02%) and 0.42% (0.03%), respectively, with a mean difference of 0.65% (95% CI, 0.64%–0.66%; P = 0). Feedback was associated with a greater number of trials associated with learning in both experiment 1 (mean difference, 1.55 trials; 95% CI, 0.15–3 trials; P = 0) and experiment 2 (mean difference, 4.25 trials; 95% CI, 1.47–7.03 trials; P = 0) and a lower number of technical errors per trial in experiments 1 (mean difference, 0.19; 95% CI, 0.07–0.30; P = .02) and 2 (mean difference, 0.58; 95% CI, 0.45–0.70; P = 0), but longer training sessions in both experiments 1 (mean difference, 9.2 minutes; 95% CI, 4.15–14.24 minutes; P = .01) and 2 (mean difference, 7.4 minutes; 95% CI, 1.17–13.59 minutes; P = .02). CONCLUSIONS: High-frequency, structured expert feedback compared favorably to self-directed learning, being associated with shorter learning curves, smaller number of technical errors, and longer duration of in-training improvement, but increased duration of the training sessions. Accepted for publication November 10, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Getúlio Rodrigues de Oliveira Filho, MD, PhD, Department of Surgery, Federal University of Santa Catarina, Rua Luiz Delfino 111/902, Florianópolis, Santa Catarina 88015, Brazil. Address e-mail to getulio.filho@ufsc.br. © 2017 International Anesthesia Research Society

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Why a Proactive Perioperative Medicine Policy Is Crucial for a Sustainable Population Health Strategy

No abstract available

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Intravenous Iron for Treatment of Anemia in the 3 Perisurgical Phases: A Review and Analysis of the Current Literature

Anemia is a common comorbidity throughout the entire hospital stay. Treatment options include intravenous (IV) iron, oral iron, erythropoietin, and red blood cell (RBC) transfusions. IV iron has gained in popularity with the implementation of patient blood management programs. A variety of studies have been performed to investigate the use of IV iron in preoperative, perioperative, and postoperative settings. An objective review on these studies has yet to be performed. The current narrative review provides an overview of trials investigating IV iron use in the preoperative, perioperative, and postoperative settings. We performed a literature research of English articles published between 1964 and March 2017 in Pubmed including Medline and The Cochrane Library. Only studies with a control group were included. The final review includes 20 randomized controlled trials (RCTs), 7 observational trials, and 5 retrospective studies. Measured outcomes included hemoglobin (Hb) levels, reticulocyte counts, and/or RBC concentrates. Meta-analyses of RCTs using IV iron administration before surgery led to an increase in Hb levels, a reduction of RBC use, and an improvement in patient outcome. Only a few studies investigated the use of IV iron in the perioperative setting. These studies recommended the use of perioperative IV iron in cases of severe anemia in orthopedic surgery but not in all types of surgery. Published RCTs in the postoperative setting have shown positive effects of IV iron on Hb levels, length of hospital stay, and transfusion requirements. Some studies demonstrated an increase of Hb of 0.5–1 g/dL over 4 weeks postoperatively, but the clinical relevance and effect of this increase on an improvement of patient's long-term outcomes are uncertain. To summarize, the evidence to use IV iron is strongest in the preoperative setting, while it remains an individual treatment decision to administer IV iron perioperatively or postoperatively. Accepted for publication September 15, 2017. Funding: A.U.S. is supported by a DFG grant (STE-1895-4/1). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrea U. Steinbicker, MD, MPH, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer Campus 1, Bldg A1, 48149 Muenster, Germany. Address e-mail to andrea.steinbicker@ukmuenster.de. © 2017 International Anesthesia Research Society

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Prospective Observational Study of Intraoperative Anesthetic Events in District Hospitals in Namibia

BACKGROUND: Access to safe surgery and anesthesia care is grossly inadequate in low- and middle-income countries, with a shortage of anesthesia providers contributing to this crisis. In Namibia, medical officers typically receive no >3 months of informal training in anesthesia. This study sought to determine the prevalence, currently unknown, of intraoperative adverse anesthetic events in this setting. Further, we assessed surgical volume, complications, and mortality outcomes at the district hospital level. METHODS: This was a prospective observational study over 7 months involving 4 district hospitals from geographically separate and diverse areas of Namibia. A standardized protocol was used to record adverse anesthetic events during surgery, surgical volume, and complications including mortality. RESULTS: A total of 737 surgical procedures were performed during the study period. There was a 10% prevalence of adverse anesthetic events intraoperatively. Of these, 70% were related to hypotension and 17% due to hypoxia and/or difficult/failed intubation. Ninety-eight percent of patients were classed as low risk (American Society of Anesthesiologists I or II). Seventy-two percent of the surgical workload was in obstetrics and gynecology, with over half being for urgent obstetrics. Perioperative mortality rate was 1.4/1000, with an overall surgical complication rate of 1.6% and a surgical infection rate of 0.8%. CONCLUSIONS: We found a 10% prevalence of adverse anesthetic events intraoperatively when anesthesia was administered by medical officers with no >3 months of informal training in this low-resource environment. The patients were considered low risk by the medical officers responsible for the anesthesia, yet these events had the potential to lead to patient harm. Accepted for publication October 23, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrew J. Ottaway, BMBS, MPH, FANZCA, Hobart Anaesthetic Group, 303 Macquarie St, Hobart, Tasmania 7000, Australia. Address e-mail to aottaway@internode.on.net. © 2017 International Anesthesia Research Society

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Continuous Noninvasive Arterial Pressure Monitoring Using the Vascular Unloading Technique (CNAP System) in Obese Patients During Laparoscopic Bariatric Operations

BACKGROUND: Increasing rates of obesity create new challenges for hemodynamic monitoring in the perioperative phase. Continuous monitoring of arterial pressure (AP) is important in severely obese patients who are at particular risk for cardiovascular complications. Innovative technologies for continuous noninvasive AP monitoring are now available. In this study, we aimed to compare continuous noninvasive AP measurements using the vascular unloading technique (CNAP system; CNSystems, Graz, Austria) compared with invasive AP measurements (radial arterial catheter) in severely obese patients during laparoscopic bariatric surgery. METHODS: In 29 severely obese patients (mean body mass index 48.1 kg/m2), we simultaneously recorded noninvasive and invasive AP measurements over a period of 45 minutes and averaged the measurements using 10-second episodes. We compared noninvasive (test method) and invasive (reference method) AP measurements using Bland-Altman analysis and 4-quadrant plot/concordance analysis (2-minute interval). RESULTS: We observed a mean of the differences (±SD, 95% limits of agreement) between the AP values obtained by the CNAP system and the invasively assessed AP values of 7.9 mm Hg (±9.6 mm Hg, −11.2 to 27.0 mm Hg) for mean AP, 4.8 mm Hg (±15.8 mm Hg, −26.5 to 36.0 mm Hg) for systolic AP, and 9.5 mm Hg (±10.3 mm Hg, −10.9 to 29.9 mm Hg) for diastolic AP, respectively. The concordance rate was 97.5% for mean AP, 95.0% for systolic AP, and 96.7% for diastolic AP, respectively. CONCLUSIONS: In the setting of laparoscopic bariatric surgery, continuous noninvasive AP monitoring with the CNAP system showed good trending capabilities compared with continuous invasive AP measurements obtained with a radial arterial catheter. However, absolute CNAP- and arterial catheter–derived AP values were not interchangeable. Accepted for publication September 27, 2017. Funding: CNSystems Medizintechnik AG (Graz, Austria) provided the technical equipment for the study. CNSystems Medizintechnik AG was not involved in the collection of the data, drafting of the manuscript, or decision to submit the manuscript for publication. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Dorothea E. Rogge, MD, Department of Anesthesiology, Centre of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Address e-mail to d.rogge@uke.de. © 2017 International Anesthesia Research Society

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Misaligned Feeding May Aggravate Pain by Disruption of Sleep–Awake Rhythm

BACKGROUND: Increasing evidence suggests that patients with eating disorders are more likely to develop chronic pain. A misaligned diet has been reported to disrupt the sleep–awake rhythms. Combined with our previous investigation on circadian pain, we aimed to investigate the role of misaligned diet in the pain sensitivity and the underlying mechanisms. METHODS: Two-month-old C57BL/6J male mice were administered chronic constriction injury (CCI) surgery to establish neuropathic pain models. CCI mice were randomized to scheduled food access throughout the whole day (CCI-free), during the daytime (CCI-misaligned), and at night (CCI-aligned), respectively. The paw withdrawal mechanical threshold, indicating pain behavior, was measured by Von Frey. The gross motor activity pattern indicating the sleep–awake rhythm was monitored by Mini-Mitter. Melatonin (Mel) was administered to ameliorate the sleep–awake rhythm (CCI-free + Mel and CCI-misaligned + Mel). The expressions of circadian pain–related proteins were detected by quantitative polymerase chain reaction and western blot. The primary outcome is the pain threshold and the secondary outcome is the sleep–awake rhythm. RESULTS: Misaligned diet during the peri-CCI surgery period significantly decreased the paw withdrawal mechanical threshold compared with the CCI-free mice (day 14: 0.40 ± 0.09 vs 0.64 ± 0.15; P = .03;) and altered the sleep–awake rhythm. Mel pretreatment alleviated the increased pain (day 14, CCI-misaligned + Mel versus CCI-misaligned: day 14: 0.60 ± 0.13 vs 0.35 ± 0.12; P = .022) and the disrupted sleep–awake rhythm caused by misaligned feeding. The mRNA levels of N-methyl-D-aspartate receptor subtype 2B (NR2B), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and cyclic adenosine monophosphate-response element binding protein (CREB) in the spinal dorsal horn increased in CCI-misaligned mice compared with the CCI-free mice. The phosphor-NR2B, phosphor-CaMKII, and phosphor-CREB also increased in CCI-misaligned mice compared with the CCI-free mice. However, the expressions of NR2B, CaMKII, and CREB were decreased in CCI-misaligned + Mel mice compared to CCI-misaligned mice at both transcriptional and translational levels. CONCLUSIONS: Misaligned diet might aggravate pain sensitivity through the disruption of the sleep–awake cycle, which could be recovered by Mel. NR2B-CaMKII-CREB may participate in the disruption of sleep–awake rhythm–mediated pain aggravation. Accepted for publication November 2, 2017. Funding: This study was supported by National Natural Science Foundation of China (81371207, 81171047, 81070892, and 81171048), Natural Science Foundation of Jiangsu Province (BK2010105), and the Grant from the Department of Health of Jiangsu Province of China (XK201140, RC2011006). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). The first authors Xu and Zhao contributed equally to this study. The authors Ma and Gu contributed equally to this study. Reprints will not be available from the authors. Address correspondence to Xiaoping Gu, PhD, MD, and Zhengliang Ma, PhD, MD, Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, 321 Zhong Shan Rd, Nanjing, Jiangsu 210008, People's Republic of China. Address e-mail to xiaopinggu@nju.edu.cn and mazhengliang1964@nju.edu.cn. © 2017 International Anesthesia Research Society

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Extracorporeal Membrane Oxygenation Appropriateness: An Interdisciplinary Consensus-Based Approach

We describe a quality improvement initiative aimed at achieving interdisciplinary consensus about the appropriate delivery of extracorporeal membrane oxygenation (ECMO). Interdisciplinary rounds were implemented for all patients on ECMO and addressed whether care was consistent with a patient's minimally acceptable outcome, maximally acceptable burden, and relative likelihood of achieving either. The rounding process was associated with decreased days on venoarterial ECMO, from a median of 6 days in 2014 (first quartile [Q1]–third quartile [Q3], 3–10) to 5 days in 2015 (Q1–Q3, 2.5–8) and in 2016 (Q1–Q3, 1–8). Our statistical methods do not allow us to conclude that this change was due to our intervention, and it is possible that the observed decreases would have occurred whether or not the rounding process was implemented. Accepted for publication October 26, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael Nurok, MBChB, PhD, Division of Cardiac Surgery, Department of Surgery and Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, 127 San Vicente Blvd, Suite 3100, Los Angeles, CA 90048. Address e-mail to michael.nurok@cshs.org. © 2017 International Anesthesia Research Society

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More Than Meets the Eye in Using Interleukin 6 as a Marker of Inflammation and Prognostic Factor for Patients With Cirrhosis

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Long-Term Return to Functional Baseline After Mechanical Ventilation in the ICU

Objective: Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes. Design: Population-based, observational cohort study. Setting: Eight adult ICUs of a single center. Patients: All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009. Interventions: None. Measurements and Main Results: In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation. Conclusions: At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation. This work was performed at the Mayo Clinic, Rochester, MN. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported by the Mayo Clinic Foundation and Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic. The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the article for publication. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wilson.michael1@mayo.edu Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Oxygen Exposure Resulting in Arterial Oxygen Tensions Above the Protocol Goal Was Associated With Worse Clinical Outcomes in Acute Respiratory Distress Syndrome

Objectives: High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients with acute respiratory distress syndrome. Participants enrolled in Acute Respiratory Distress Syndrome Network trials had a goal partial pressure of oxygen in arterial blood range of 55–80 mm Hg, yet the effect of oxygen exposure above this arterial oxygen tension range on clinical outcomes is unknown. We sought to determine if oxygen exposure that resulted in a partial pressure of oxygen in arterial blood above goal (> 80 mm Hg) was associated with worse outcomes in patients with acute respiratory distress syndrome. Design: Longitudinal analysis of data collected in these trials. Setting: Ten clinical trials conducted at Acute Respiratory Distress Syndrome Network hospitals between 1996 and 2013. Subjects: Critically ill patients with acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: We defined above goal oxygen exposure as the difference between the fraction of inspired oxygen and 0.5 whenever the fraction of inspired oxygen was above 0.5 and when the partial pressure of oxygen in arterial blood was above 80 mm Hg. We then summed above goal oxygen exposures in the first five days to calculate a cumulative above goal oxygen exposure. We determined the effect of a cumulative 5-day above goal oxygen exposure on mortality prior to discharge home at 90 days. Among 2,994 participants (mean age, 51.3 yr; 54% male) with a study-entry partial pressure of oxygen in arterial blood/fraction of inspired oxygen that met acute respiratory distress syndrome criteria, average cumulative above goal oxygen exposure was 0.24 fraction of inspired oxygen-days (interquartile range, 0–0.38). Participants with above goal oxygen exposure were more likely to die (adjusted interquartile range odds ratio, 1.20; 95% CI, 1.11–1.31) and have lower ventilator-free days (adjusted interquartile range mean difference of –0.83; 95% CI, –1.18 to –0.48) and lower hospital-free days (adjusted interquartile range mean difference of –1.38; 95% CI, –2.09 to –0.68). We observed a dose-response relationship between the cumulative above goal oxygen exposure and worsened clinical outcomes for participants with mild, moderate, or severe acute respiratory distress syndrome, suggesting that the observed relationship is not primarily influenced by severity of illness. Conclusions: Oxygen exposure resulting in arterial oxygen tensions above the protocol goal occurred frequently and was associated with worse clinical outcomes at all levels of acute respiratory distress syndrome severity. Dr. Aggarwal contributed to this article as an employee of Johns Hopkins University. The views expressed in this article are his own and those of Johns Hopkins University School of Medicine, and do not necessarily represent the views of the National Institutes of Health or the U.S. government. Drs. Aggarwal, Brower, and Checkley contributed in conception and design of the work. Drs. Aggarwal and Checkley contributed in analysis and interpretation of the data. Drs. Aggarwal, Brower, Hager, Thompson, Netzer, and Shanholtz, Mr. Lagakos, and Dr. Checkley contributed in drafting the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported, in part, by grant from National Heart, Lung, and Blood Institute (NHLBI) Contracts NO1-HR-46054 through 46064 and NO1-HR 56165 through 56179 with the National Institutes of Health, NHLBI. The funding agencies had no role in study design or conduct, or in the writing of this report. Drs. Aggarwal, Thompson, Shanholtz, and Checkley received support for article research from the National Institutes of Health (NIH). Dr. Aggarwal was supported by a Fellow-to-Faculty Award (11FTF7280014) from the American Heart Association. Dr. Brower received funding from Applied Clinical Intelligence and Global Blood Therapeutics. Dr. Thompson received funding from consultancy for Alexion, Asahi Kasei, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Vertex, and Regeneron unrelated to the current work. Dr. Shanholtz's institution received funding from the NIH National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Dr. Checkley was supported by a Pathway to Independence Award (R00HL096955) from the National Heart, Lung and Blood Institute, NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wcheckl1@jhmi.edu Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Cardiac Arrest and Mortality Related to Intubation Procedure in Critically Ill Adult Patients: A Multicenter Cohort Study

Objectives: To determine the prevalence of and risk factors for cardiac arrest during intubation in ICU, as well as the association of ICU intubation–related cardiac arrest with 28-day mortality. Design: Retrospective analysis of prospectively collected data. Setting: Sixty-four French ICUs. Patients: Critically ill patients requiring intubation in the ICU. Interventions: None. Measurements and Main Results: During the 1,847 intubation procedures included, 49 cardiac arrests (2.7%) occurred, including 14 without return of spontaneous circulation (28.6%) and 35 with return of spontaneous circulation (71.4%). In multivariate analysis, the main predictors of intubation-related cardiac arrest were arterial hypotension (systolic blood pressure 25 kg/m2; odds ratio = 2.005 [1.017–3.951]; p = 0.0445), and age more than 75 years old (odds ratio = 2.251 [1.080–4.678]; p = 0.0297). Overall 28-day mortality rate was 31.2% (577/1,847) and was significantly higher in patients who experienced intubation-related cardiac arrest than in noncardiac arrest patients (73.5% vs 30.1%; p

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Association Between Partial Pressure of Arterial Carbon Dioxide and Survival to Hospital Discharge Among Patients Diagnosed With Sepsis in the Emergency Department

Objective: The objective of this study was to test the association between the partial pressure of arterial carbon dioxide and survival to hospital discharge among mechanically ventilated patients diagnosed with sepsis in the emergency department. Design: Retrospective cohort study of a single center trial registry. Setting: Academic medical center. Patients: Mechanically ventilated emergency department patients. Inclusion criteria: age 18 years and older, diagnosed with sepsis in the emergency department, and mechanical ventilation initiated in the emergency department. Interventions: Arterial blood gases obtained after initiation of mechanical ventilation were analyzed. The primary outcome was survival to hospital discharge. We tested the association between partial pressure of arterial carbon dioxide and survival using multivariable logistic regression adjusting for potential confounders. Sensitivity analyses, including propensity score matching were also performed. Measurements and Main Results: Six hundred subjects were included, and 429 (72%) survived to hospital discharge. The median (interquartile range) partial pressure of arterial carbon dioxide was 42 (34–53) mm Hg for the entire cohort and 44 (35–57) and 39 (31–45) mm Hg among survivors and nonsurvivors, respectively (p

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Platelet Drop and Fibrinolytic Shutdown in Patients With Sepsis

Objective: Thrombocytopenia is the most common hemostatic disorder during sepsis and is associated with high mortality. We examined whether fibrinolytic changes precede incident thrombocytopenia and predict outcome in patients with severe sepsis. Design: Nested study from the multicenter, randomized, controlled trial on the efficacy of albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Setting: Forty ICUs in Italy. Patients: Three groups of patients were selected: 1) patients with platelet count less than or equal to 50 × 109/L at study entry (n = 85); 2) patients with baseline platelet count greater than or equal to 100 × 109/L who developed thrombocytopenia (≤ 50 × 109/L) within 28 days (n = 100); 3) patients with platelet count always more than or equal to 100 × 109/L (n = 95). Interventions: Fibrinolytic variables, including fibrinolysis inhibitors and in vivo markers of plasmin generation, were measured on day 1. Measurements and Main Results: Patients with early thrombocytopenia (group 1) and those who developed it later (group 2) had similar illness severity and 90-day mortality, whereas patients without thrombocytopenia (group 3) had milder disease and lower mortality. Fibrinolysis was markedly (and similarly) depressed in groups 1 and 2 as compared with group 3. Major fibrinolytic changes included increased levels of plasminogen activator inhibitor 1 and extensive activation/consumption of thrombin activatable fibrinolysis inhibitor. Most fibrinolytic variables were significantly associated with mortality in univariate models. However, only thrombin activatable fibrinolysis inhibitor level and in vivo markers of fibrinolysis activation, namely plasmin-antiplasmin complex, and D-dimer, were independently associated with mortality after adjustment for Simplified Acute Physiology Score-II score, sex, and platelet count. Furthermore, the coexistence of impaired fibrinolysis and low platelets was associated with an even greater mortality. Conclusions: Impaired fibrinolysis, mainly driven by plasminogen activator inhibitor-1 increase and thrombin activatable fibrinolysis inhibitor activation, is an early manifestation of sepsis and may precede the development of thrombocytopenia. Thrombin activatable fibrinolysis inhibitor level, in particular, proved to be an independent predictor of mortality, which may improve risk stratification of patients with severe sepsis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported by grants from the Italian Medicines Agency (AIFA, grant FARM6JS3R5, 2006), the Italian Ministry of Health (Ricerca Finalizzata 2011–2012, grant RF-2011-02348358), and by a grant from Università degli Studi di Bari Aldo Moro. Dr. Colucci received support for article research from Università degli Studi di Bari Aldo Moro (IT). Drs. Gattinoni, Masson, Teli, Magnoli, Latini, and Pesenti's institutions received funding from Italian Medicines Agency (AIFA, grant FARM6JS3R5, 2006) and Italian Ministry of Health (Ricerca Finalizzata 2011–2012, grant RF-2011-02348358). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: mario.colucci@uniba.it Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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The Cumulative Partial Pressure of Arterial Oxygen Is Associated With Neurological Outcomes After Cardiac Arrest Treated With Targeted Temperature Management

Objective: Hyperoxia could lead to a worse outcome after cardiac arrest. The aim of this study was to investigate the relationship between the cumulative partial pressure of arterial oxygen (PaO2) and neurological outcomes after cardiac arrest treated with targeted temperature management. Design: Retrospective analysis of a prospective cohort. Setting: An academic tertiary care hospital. Patients: A total of 187 consecutive patients treated with targeted temperature management after cardiac arrest. Interventions: None. Measurements and Main Results: The area under the curve of PaO2 for different cutoff values of hyperoxia (≥ 100, ≥ 150, ≥ 200, ≥ 250, and ≥ 300 mm Hg) with different time intervals (0–24, 0–6, and 6–24 hr after return of spontaneous circulation) was calculated for each patient using the trapezoidal method. The primary outcome was the neurologic outcome, as defined by the cerebral performance category, at 6 months after cardiac arrest. Of 187 subjects, 77 (41%) had a good neurologic outcome at 6 months after cardiac arrest. The median age was 54 (43–69) years, and 128 (68%) were male. The area under the curve of PaO2 with cutoff values of greater than or equal to 200, greater than or equal to 250, and greater than or equal to 300 was higher in the poor outcome group at 0–6 and 0–24 hours. The adjusted odds ratios of area under the curve of PaO2 greater than or equal to 200 mm Hg were 1.659 (95% CI, 1.194–2.305) for 0–24 hours after return of spontaneous circulation and 1.548 (95% CI, 1.086–2.208) for 0–6 hours after return of spontaneous circulation. With a higher cumulative exposure to oxygen tension, we found significant increasing trends in the adjusted odds ratio for poor neurologic outcomes. Conclusion: In a new method for PaO2 analysis, cumulative exposure to hyperoxia was associated with neurologic outcomes in a dose-dependent manner. Greater attention to oxygen supply during the first 6 hours appears to be important for outcome after cardiac arrest. This study was approved by the Institutional Review Board of Seoul St. Mary's Hospital; waiver of consent was allowed because of the retrospective nature of the study. The statistical analysis of this study was performed by Hyeon Woo Yim, MD, at the Clinical Research Coordinating Center, Departments of Preventive Medicine, College of Medicine, The Catholic University of Korea. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: emsky@catholic.ac.kr Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Pediatric In-Hospital Cardiac Arrest Secondary to Acute Pulmonary Embolism

Objectives: Pulmonary embolism is a rarely reported and potentially treatable cause of cardiac arrest in children and adolescents. The objective of this case series is to describe the course of five adolescent patients with in-hospital cardiac arrest secondary to pulmonary embolism. Design: Case series. Setting: Single, large academic children's hospital. Patients: All patients under the age of 18 years (n = 5) who experienced an in-hospital cardiac arrest due to apparent pulmonary embolism from August 1, 2013, to July 31, 2017. Interventions: All five patients received systemic thrombolytic therapy (IV tissue plasminogen activator) during cardiac arrest or periarrest during ongoing resuscitation efforts. Measurements and Main Results: Five adolescent patients, 15–17 years old, were treated for pulmonary embolism–related cardiac arrests during the study period. These accounted for 6.3% of all children and 25% of adolescents (12–17 yr old) receiving at least 5 minutes of in-hospital cardiopulmonary resuscitation during the study period. All five had venous thromboembolism risk factors. Two patients had known, extensive venous thrombi at the time of cardiac arrest, and one was undergoing angiography at the time of arrest. The diagnoses of pulmonary embolism were based on clinical suspicion, bedside echocardiography (n = 4), and low end-tidal CO2 levels relative to arterial CO2 values (n = 5). IV tissue plasminogen activator was administered during cardiopulmonary resuscitation in three patients and after the return of spontaneous circulation, in the setting of severe hemodynamic instability, in the other two patients. Four of five patients were successfully resuscitated and survived to hospital discharge. Conclusions: Pulmonary embolism was recognized as the etiology of multiple adolescent cardiac arrests in this single-center series and may be more common than previously reported. Recognition, high-quality cardiopulmonary resuscitation, and treatment with thrombolytic therapy resulted in survival in four of five patients. Drs. Morgan and Stinson are cofirst authors. Dr. Topjian received support for article research from the National Institutes of Health. Dr. Sutton's institution received funding from the National Heart, Lung, and Blood Institute; he received funding from Zoll Medical (speaking honoraria); and he disclosed that he is a member of the American Heart Association's Get with the Guidelines Pediatric Research Task Force. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: morganr1@email.chop.edu Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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New Research From Clinical Psychological Science

Read about the latest research published in Clinical Psychological Science:

The Impact of Affective Context on Autobiographical Recollection in Depression  

Caitlin Hitchcock, Ann-Marie J. Golden, Aliza Werner-Seidler, Willem Kuyken, and Tim Dalgleish

Context influences the autobiographical memories people retrieve in a given situation, sometimes eliciting memories that are unwanted. Research suggests that people with depression may have more difficulty overriding context in such situations. The authors devised a new task to investigate this phenomenon, asking individuals with varying degrees of clinical depression to retrieve negative autobiographical memories in response to cue words that were positive (e.g., cheer) or negative (e.g., misery). Although they were directed to retrieve negative memories, participants who had more severe symptoms retrieved more positive memories in response to the positive cues compared with those who had less severe symptoms. The findings suggest that depression may have diminished participants' ability to override the positive contextual cues. A similar study with participants from a community sample showed that lower working memory capacity was also associated with the retrieval of more positive memories in response to positive cue words. The authors conclude that executive control underlies the ability to override context in memory retrieval, and they discuss how cognitive training might help reduce depressed individuals' susceptibility to context.

Emotion Regulation Predicts Everyday Emotion Experience and Social Function in Schizophrenia  

Erin K. Moran, Adam J. Culbreth, and Deanna M. Barch

Which emotion-regulation strategies do people with schizophrenia employ and how do these strategies relate to daily functioning? Using ecological momentary assessment, the authors measured the emotional experiences and social interactions of individuals with schizophrenia over a 7-day period. Each day, participants received four daytime cell-phone prompts asking them to report their momentary experiences of both positive and negative emotions (i.e., happy, calm, sad, and anxious); a nighttime prompt asked about their social interactions and daily social interest. After 7 days, participants completed a questionnaire that assessed the degree to which they used cognitive reappraisal and suppression as emotion-regulation strategies; the questionnaire also measured their ability to savor positive emotions. The data showed that greater use of cognitive reappraisal was associated with more positive emotions in daily life and that savoring of emotional experiences was associated with more positive emotions, greater social interactions and interest, and decreased negative emotions. In contrast, greater suppression was associated with greater negative emotion, decreased social interaction and interest, and decreased positive emotions. The authors conclude that individual differences in how individuals with schizophrenia use emotion-regulation strategies may affect everyday social and emotional experiences.

Gaze Following Is Related to the Broader Autism Phenotype in a Sex-Specific Way: Building the Case for Distinct Male and Female Autism Phenotypes  

Elisabeth M. Whyte and K. Suzanne Scherf

Autism is less likely to be diagnosed in females than in males, resulting in insufficient data on potential sex differences in the autism phenotype. This study investigated whether sex differences might emerge in eye-gaze processing, thought to be a core deficit in autism. Using an "extreme subjects" design, the authors recruited a nonclinical sample of adult men and women who exhibited either high or low levels of autistic-like traits (ALTs). The participants viewed a series of images showing a person among multiple objects – after each image, they indicated what the person was looking at by choosing one of four options (i.e., a target object, a plausible nontarget object, or one of two implausible nontarget objects). Men who had high levels of ALTs showed poorer eye-gaze following than both men with low ALTs and women with high ALTs. Women's performance on the eye-gaze task did not vary according to ALTs. The authors suggest that abnormal eye-gaze processing may be part of the broader male autism phenotype but not the female autism phenotype.

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Physiatry Reviews for Evidence in Practice (PREP) Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist: Effect of Inpatient Rehabilitation vs a Monitored Home-Based Program on Mobility in Patients With Total Knee Arthroplasty The HIHO Randomized Clinical Trial.

No abstract available

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Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults with Mild Cognitive Impairment and Intact Cognition

ABSTRACTOBJECTIVEThis study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment (aMCI) and normal cognition (NC), and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia.DESIGNThis was a cross sectional study of 46 community dwelling older adults, ages 70–95 with aMCI (n=23) and NC (n=23). Structural magnetic resonance imaging (MRI) was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function.RESULTSDuring fast paced walking, older adults with aMCI demonstrated significantly slower gait speed and shorter stride length compare to older adults with NC. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P

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Intraarticular Triamcinolone versus Hyaluronate Injections for Low Back Pain with Symptoms Suggestive of Lumbar Zygapophyseal Joint Arthropathy: A Pragmatic, Double Blind Randomized Controlled Trial

AbstractObjectiveTo compare hyaluronate to triamcinolone injections in treating chronic low back pain (CLBP) suggestive of lumbar zygopophyseal joint (ZJT) arthropathy.DesignProspective, double-blind, randomized controlled trial. 30 subjects were randomly assigned to receive bilateral L3-S1 ZJT injections with triamcinolone (KA) or Synvisc-One® (HA). Pain [Visual Analog Scale (VAS)] and Pain Disability Questionnaire (PDQ) scores at 1, 3, and 6-months were evaluated.ResultsNo significant inter-group differences (p>.05) in outcomes were noted in the 30 recruited subjects. (KA/HA, baseline; 1-month; 3-month; 6-month)-VAS scores: 70±15/74±10; 58±29/45±25; 58±29/56±25; 59±28/63±24. PDQ scores: 100±23/102±28; 77±30/74±34; 87±26/74±36; 96±25/79±25. Overall percent improvement@6months: KA(51±35) and HA(42±33) [p=.51]. HA group VAS scores improved significantly (70±20 to 45±25@1m, p=.008). PDQ scores improved at 1m (100±23 to 77±30, p=.009) in the KA group and at all time points in the HA group (102±28 to 74±34@1m, p=.002; 74±36@3m, p=.037; 79@6m [Median; 52-99.5, p<.001 medians and quartiles were used in statistical analysis when data did not pass normality.conclusionspatients with clbp suggestive of lumbar zjt arthropathy responded similarly to triamcinolone or hyaluronate injections. ha group showed significant short- long-term functional improvement short-term pain ka only benefit no improvement. objective compare injections treating chronic low back zygopophyseal joint arthropathy. design prospective double-blind randomized controlled trial. subjects randomly assigned receive bilateral l3-s1 synvisc-one analog scale disability questionnaire scores at evaluated. results inter-group differences>.05) in outcomes were noted in the 30 recruited subjects. (KA/HA, baseline; 1-month; 3-month; 6-month)-VAS scores: 70±15/74±10; 58±29/45±25; 58±29/56±25; 59±28/63±24. PDQ scores: 100±23/102±28; 77±30/74±34; 87±26/74±36; 96±25/79±25. Overall percent improvement@6months: KA(51±35) and HA(42±33) [p=.51]. HA group VAS scores improved significantly (70±20 to 45±25@1m, p=.008). PDQ scores improved at 1m (100±23 to 77±30, p=.009) in the KA group and at all time points in the HA group (102±28 to 74±34@1m, p=.002; 74±36@3m, p=.037; 79@6m [Median; 52-99.5, p<.001 medians and quartiles were used in statistical analysis when data did not pass normality. conclusions patients with clbp suggestive of lumbar zjt arthropathy responded similarly to triamcinolone or hyaluronate injections. ha group showed significant short- long-term functional improvement short-term pain ka only benefit no improvement. affiliation where the research was conducted correspondence: thiru m. annaswamy md ma s. lancaster road dallas tx-75216. email: thiru.annaswamy author disclosures: this funded by any grant foundation agency. paper is report a clinical trial. however trial time period at which point there requirements for all trials be registered. therefore rct does have registration registry. abstract previously presented at: tm armstead c avraham r carlson l bierner sm. scientific presentations: intraarticular vs. injections zygapophyseal joint arthropathy: pragmatic double blind randomized controlled presentation. annual assembly aapmr. boston ma. september pm page s91. doi: http: versus abstracts papers posters meeting association academic physiatrists san antonio tx. american journal physical medicine rehabilitation supplement a6-a7. march copyright wolters kluwer health inc. rights reserved.>

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IMMUNE RESPONSES OF HLA-HIGHLY-SENSITIZED AND NONSENSITIZED PATIENTS TO GENETICALLY-ENGINEERED PIG CELLS

AbstractBackgroundWe investigated in vitro whether HLA-highly-sensitized patients with end-stage renal disease (ESRD) will be disadvantaged immunologically after a genetically-engineered pig kidney transplant.MethodsBlood was drawn from patients with a cPRA 99-100% (Gp1, n=10) or cPRA 0% (Gp2, n=12), and from healthy volunteers (Gp3, n=10). Serum IgM and IgG binding was measured (i) to Gal and Neu5Gc glycans by ELISA, and (ii) to pRBC, pAEC, and pPBMC from GTKO/CD46 and GTKO/CD46/CMAHKO pigs by flow cytometry. (iii) T and B cell phenotypes were determined by flow cytometry, and (iv) proliferation of T and B cells CFSE-MLR.Results(i) By ELISA, there was no difference in IgM or IgG binding to Gal or Neu5Gc between Gps1 and 2, but binding was significantly reduced in both groups compared to Gp3. (ii) IgM and IgG binding in Gps1 and 2 was also significantly lower to GTKO/CD46 pig cells than in healthy controls, but there were no differences between the 3 groups in binding to GTKO/CD46/CMAHKO cells. (iii and iv) Gp1 patients had more memory T cells than Gp2, but there was no difference in T or B cell proliferation when stimulated by any pig cells. The proliferative responses in all 3 groups were weakest when stimulated by GTKO/CD46/CMAHKO pPBMC.Conclusions(i) ESRD was associated with low anti-pig antibody levels. (ii) Xenoreactivity decreased with increased genetic engineering of pig cells. (iii) High cPRA status had no significant effect on antibody binding or T and B cell response. Background We investigated in vitro whether HLA-highly-sensitized patients with end-stage renal disease (ESRD) will be disadvantaged immunologically after a genetically-engineered pig kidney transplant. Methods Blood was drawn from patients with a cPRA 99-100% (Gp1, n=10) or cPRA 0% (Gp2, n=12), and from healthy volunteers (Gp3, n=10). Serum IgM and IgG binding was measured (i) to Gal and Neu5Gc glycans by ELISA, and (ii) to pRBC, pAEC, and pPBMC from GTKO/CD46 and GTKO/CD46/CMAHKO pigs by flow cytometry. (iii) T and B cell phenotypes were determined by flow cytometry, and (iv) proliferation of T and B cells CFSE-MLR. Results (i) By ELISA, there was no difference in IgM or IgG binding to Gal or Neu5Gc between Gps1 and 2, but binding was significantly reduced in both groups compared to Gp3. (ii) IgM and IgG binding in Gps1 and 2 was also significantly lower to GTKO/CD46 pig cells than in healthy controls, but there were no differences between the 3 groups in binding to GTKO/CD46/CMAHKO cells. (iii and iv) Gp1 patients had more memory T cells than Gp2, but there was no difference in T or B cell proliferation when stimulated by any pig cells. The proliferative responses in all 3 groups were weakest when stimulated by GTKO/CD46/CMAHKO pPBMC. Conclusions (i) ESRD was associated with low anti-pig antibody levels. (ii) Xenoreactivity decreased with increased genetic engineering of pig cells. (iii) High cPRA status had no significant effect on antibody binding or T and B cell response. Address Correspondence to: Martin Wijkstrom, MD, Thomas E Starzl Transplantation Institute, Montefiore University Hospital, MUH 756.2, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA. Email: wijkstrommn@upmc.edu Author Contributions: All authors participated in revising and approving the manuscript. ZZ, HQ, HH, MW, DKCC designed and initiated this study. ZZ, CL, IH, HH participated in laboratory assay. Data were collected and analyzed by ZZ, CL, HH, CM, MM, AZ, ME, MW, DKCC. The manuscript was prepared by ZZ, HH, ME, CM, AZ, MW, DKCC. Genetically-engineered pig cells were provided by DA. Conflicts of interest: David Ayares is an employee of Revivicor, Inc. No other author has a conflict of interest. Funding: Zhongqiang Zhang was supported by the China Scholarship Council (File No. 201506370112). Work on xenotransplantation in the Thomas E. Starzl Transplantation Institute of the University of Pittsburgh is, or has been, supported in part by NIH grants #U19 AI090959, #U01 AI068642, and # R21 A1074844, and by Sponsored Research Agreements between the University of Pittsburgh and Revivicor, Inc., Blacksburg, VA. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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E-Healthcare for Celiac Disease—A Multicenter Randomized Controlled Trial

To evaluate the (cost-)effectiveness of online consultations in follow-up of patients with celiac disease (CD).

http://ift.tt/2DpbHZV

New Onset Autoimmune Hepatitis during Anti-Tumor Necrosis Factor-Alpha Treatment in Children

To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use.

http://ift.tt/2p646MP

Timing of Surgical Resection for Curative Colorectal Cancer with Liver Metastasis

Abstract

Purpose and Design

Optimal surgical strategy for resectable synchronous colorectal cancer with liver metastasis (SCRLM) remains a therapeutic dilemma. Multiple retrospective studies including several meta-analyses have been published since 2001 to help facilitate the decision making process and identify the optimal surgical approach. Controversy limits the generalization of available data to draw conclusions. A review of available literature on appropriate surgical timing may alleviate confusion among physicians and promote a more evidence based approach.

Results and Conclusion

Current evidence supports the feasibility, safety, and equivalent oncological outcomes of simultaneous curative resection of stage IV colorectal cancer with liver metastasis in appropriately selected patients.

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Factors Associated with 60-Day Readmission Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy

Abstract

Introduction

Readmission rates following surgery are subject to scrutiny in efforts to control health care costs. This study was designed to define the 60-day readmission rate following cytoreduction and HIPEC at a high-volume center and to identify factors associated with readmission.

Methods

Patients who underwent complete cytoreduction and HIPEC at a single institution from August 2007 through June 2014 were identified from a prospectively maintained database. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day readmission following surgery.

Results

A total of 250 patients were identified. Forty patients (17%) experienced readmission within 60 days of surgery. The most common reasons for readmission were ileus/dehydration (12, 31%), deep space infection (8, 21%), and DVT/PE (6, 15%). Initial postoperative length of stay was longer for patients readmitted within 60 days (median 12 vs. 9 days, p = 0.013). Of categorical variables analyzed, including gender, histology, HIPEC agent, intraoperative transfusion, and individual procedures performed during cytoreduction, adjuvant systemic therapy, and postoperative morbidity, only Charlson comorbidity index CCI (odds ratio (OR) = 3.80 [1.68–8.60]) and stoma creation (OR = 6.04 [1.56–12.14]) were associated with 60-day readmission.

Conclusions

Few measurable variables are associated with readmission following cytoreduction and HIPEC. Patients with high CCI and those with stomas created at the time of CRS/HIPEC may be at increased risk of readmission within 60 days. Earlier or more frequent follow-up for high-risk patients should be considered as a strategy to reduce readmissions.

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Cervicothoracoscopic Approach in Esophagectomy

Abstract

Backgrounds

Esophageal cancer frequently metastasizes to lymph nodes along the recurrent laryngeal nerve (RLN).1 Therefore, it is essential to dissect RLN nodes for curative esophagectomy. Complete RLN node dissection without injury to the organs at the cervicothoracic junction requires experienced techniques. This report describes the cervicothoracoscopic approach, whereby the complete dissection can be safely performed.

Methods

With this approach, both cervical and laparoscopic procedures are performed in the open-leg supine position before the thoracoscopic procedure is performed in the prone position. For RLN node dissection, the paratracheal lymphatic chain is detached from RLNs at the cervicothoracic junction in the cervical operation field, and the detached tissue is retrieved together with the mediastinal RLN lymph nodes via thoracoscopy. This approach was applied to all squamous cell carcinoma patients and to patients with Siewert type 1 tumors of stage 2 or more, except for patients with clinically suspected T4 tumors.

Results

Of 91 patients, 27 (29.7%) experienced RLN palsy and 15 (16.5%) experienced postoperative pneumonia. Hoarseness due to RLN palsy was improved in almost all the patients within 6 postoperative months, and persistent paralysis was seldom observed. Within 30 days, neither a reoperation nor a hospital mortality occurred.

Conclusions

The cervicothoracoscopic approach enables complete en bloc dissection of the lymphatic chain that lies along RLN in the cervicothoracic junction. Also, with this approach, RLNs can be identified easily because RLNs are already exposed at the upper mediastinum by the cervical procedure. Therefore, this approach may contribute to improving the surgical curability and preventing RLN injury.

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