Biomarkers and postoperative cognitive function: could it be that easy?

Purpose of review Neurocognitive dysfunction after surgery is highly relevant in the elderly. The multifactorial manner of this syndrome has made it hard to define an ideal biomarker to predict individual risk and assess diagnosis and severity of delirium [postoperative delirium (POD)] and subsequent postoperative cognitive decline (POCD). This review summarizes recent literature on blood biomarkers for POD/POCD. Recent findings Markers for delirium have been searched for in the cerebrospinal fluid to examine the pathologic cascade. However, cerebrospinal fluid cannot be easily obtained in the perioperative setting. Thus, attention shifts toward prediction markers from patients' blood to determine the individual risk. In this regard, three major groups of peripheral blood markers could be distinguished: first, global, but unspecific markers associated with POD/POCD; second, specific and established markers related to neurocognitive function; and third, upcoming or newly described markers with less evidence. Solely neuron-specific enolase is an adequate biomarker based on recent literature. Summary Single markers for postoperative cognitive impairment cannot predict POD/POCD in geriatric patients. However, a wisely arranged battery of promising biomarkers might achieve a satisfying sensitivity and specificity for the preoperative assessment of subsequent cognitive decline. Adequately powered studies to prove this hypothesis are required. Correspondence to Simon T. Schaefer, Department of Anaesthesiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany. Tel: +49 89 440 013 181 142; fax: +49 89 440 078 886; e-mail: simon.schaefer@med.uni-muenchen.de 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 (https://ift.tt/1qR4umk). Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Corrigendum to “Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells”

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Expert Consensus of Syndrome Differentiation for Phlegm Turbidity Syndrome for Coronary Heart Disease

Objective. The purpose of the study was to form a questionnaire of expert consensus about phlegm turbidity syndrome of coronary heart disease (CHD) using literature method and Delphi method, which could provide the objective evidences for the clinical diagnosis and treatment for CHD. Method. The CBM, CNKI, VIP, and PubMed were searched. The articles about phlegm turbidity syndrome for CHD with the definite related four diagnostic data were included. Based on the results of the literature method, two rounds of Delphi method were conducted. The TCM experts about CHD were enrolled. Concentration and coordination index of the experts were used to select the items. Results. Literature method: A total of 118 articles were included. Greasy fur, slippery pulse, chest fullness or chest pain, anorexia, nausea and vomiting, vertigo, excessive phlegm, abdominal fullness, head heaviness, obesity, stringy pulse, physical heaviness, soft pulse, somnolence, fatigue, and pale tongue (16 items) had the relatively high proportion, and they were eligible for Delphi process. Delphi method: A total of 93 experts (22 for the first round, 71 for the second round) were included. The reliability of the items was 0.885 for all the experts. The 16 items were not significantly different between the two rounds (P>0.05). According to the results of mean, frequency, sum of ranks and coefficient of variation, the item of nausea and vomiting, somnolence, pale tongue, and soft pulse were deleted. Conclusions. The questionnaire of phlegm turbidity syndrome of CHD was established, with good reliability. The sensitivity and specificity of the questionnaire are still necessary to further validate for clinical or scientific use.

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Examination of the enhanced recovery guidelines in thoracic surgery

Purpose of review Enhanced Recovery After Thoracic Surgery (ERATS) has gained momentum over the past few years, although the evidence base and expert recommendations lag behind other specialties. This review will present and examine key points from the first guidelines for enhanced recovery after lung surgery, released in 2018, jointly sponsored by the European Society of Thoracic Surgeons and the Enhanced Recovery After Surgery Society. Recent findings The recently released guidelines present core components of enhanced recovery as they pertain to lung resection surgery. Although evidence is still sparse in some areas, the guidelines summarize the available literature and incorporate levels of recommendation based upon the strength of available data as well as expert consensus. As of yet, the relative contribution of individual ERATS components to improvement in outcomes is unclear, but overall compliance does seem to be linked to positive results. Since the creation of the guidelines, additional literature related to ERATS has been released, and it will be incorporated and discussed into our review. Summary The creation of guidelines for enhanced recovery after lung resection will provide the thoracic anesthesiologist a framework upon which to build a comprehensive perioperative anesthetic plan. Correspondence to Emily G. Teeter, MD, FASE, Department of Anesthesiology, University of North Carolina at Chapel Hill, N2198 UNC Hospitals, CB #7010, Chapel Hill, NC 27599-7010, USA. Tel: 1 (919) 966 5136; E-mail: Emily_Teeter@med.unc.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Neuromonitoring in the elderly

Purpose of review To summarize recent recommendations on intraoperative electroencephalogram (EEG) neuromonitoring in the elderly aimed at the prevention of postoperative delirium and long-term neurocognitive decline. We discuss recent perioperative EEG investigations relating to aging and cognitive dysfunction, and their implications on intraoperative EEG neuromonitoring in elderly patients. Recent findings The incidence of postoperative delirium in elderly can be reduced by monitoring depth of anesthesia, using an index number (0–100) derived from processed frontal EEG readings. The recently published European Society of Anaesthesiology guideline on postoperative delirium in elderly now recommends guiding general anesthesia with such indices (Level A). However, intraoperative EEG signatures are heavily influenced by age, cognitive function, and choice of anesthetic agents. Detailed spectral EEG analysis and research on EEG-based functional connectivity provide new insights into the pathophysiology of neuronal excitability, which is seen in elderly patients with postoperative delirium. Summary Anesthesiologists should become acquainted with intraoperative EEG signatures and their relation to age, anesthetic agents, and the risk of postoperative cognitive complications. A working knowledge would allow an optimized and individualized provision of general anesthesia for the elderly. Correspondence to Claudia Spies, Department of Anesthesiology and Operative Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. Tel: +49 30 450 651 001; e-mail: claudia.spies@charite.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Incremental value of noncerebral somatic tissue oxygenation monitoring for patients undergoing surgery

Purpose of the review There is increasing interest in the use of noncerebral somatic tissue oxygen saturation (SstO2) monitoring on the basis of near-infrared spectroscopy in patients undergoing surgery or residing in intensive care unit. The relevant question is whether SstO2 monitoring can improve the quality of care. In this article, we reviewed the clinical application of SstO2 monitoring in acute care, focusing on its use in patients undergoing surgery. Recent findings Multiple small cohort studies conducted on pediatric patients reported close associations of SstO2 measurements over different regions such as the splanchnic and renal tissue beds with systemic oxygenation, transfusion, hemodynamic indices, morbidity, and mortality. Conversely, there is paucity of literature on SstO2 monitoring in adult patients. The limited number of reports suggests that SstO2 levels over bulk muscles such as the thenar eminence, forearm, and lower leg during surgery are correlated with postoperative outcomes including postoperative nausea and vomiting and the length of hospital stay in adult patients undergoing surgery. The only pilot, randomized interventional study based on 50 patients undergoing surgery did not find a difference in outcomes on the basis of the use of SstO2 monitoring. Summary Somatic tissue oxygenation may represent an essential aspect of human physiology in acute care, and it is likely outcome-relevant based on observational cohort studies. Future research should examine whether SstO2-guided care can further improve patient outcomes using randomized controlled trials. Correspondence to Lingzhong Meng, MD, Professor and Division Chief, Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, TMP 3, PO Box 208051, New Haven, CT 06520, USA. Tel: +1 203 785 2802; e-mail: lingzhong.meng@yale.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Extravascular lung water monitoring for thoracic and lung transplant surgeries

Purpose of review Excessive accumulation of extravascular lung water (EVLW) resulting in pulmonary edema is the most feared complication following thoracic surgery and lung transplant. ICUs have long relied on chest radiography to monitor pulmonary status postoperatively but the increasing recognition of the limitations of bedside plain films has fueled development of newer technologies, which offer earlier detection, quantitative assessments, and can aide in preoperative screening of surgical candidates. In this review, we focus on the emergence of transpulmonary thermodilution (TPTD) and lung ultrasound with a focus on the clinical integration of these modalities into current intraoperative and critical care practices. Recent findings Recent studies demonstrate transpulmonary thermodilution and lung ultrasound provide greater sensitivity and earlier detection of lung water accumulation and are useful to guide clinical management. Assessments from these techniques have predictive value of postoperative outcome. Further, EVLW assessment shows promise as a preoperative screening tool in lung transplant patients. Summary Monitoring EVLW in the perioperative period offers clinicians a powerful tool to guide fluid therapy and manage pulmonary edema. Both TPTD and lung ultrasound have unique attributes in the care of thoracic surgery and lung transplant patients. Correspondence to Sherif Assaad, MD, Department of Anesthesiology, Yale University School of Medicine, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. Tel: +1 203 932 5711; fax: +1 203 937 4803; e-mail: sherif.assaad@yale.ed Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Spinal cord perfusion protection for thoraco-abdominal aortic aneurysm surgery

Purpose of Review Spinal cord ischemia (SCI) is a devastating complication after open or endovascular aortic repair for thoracoabdominal aortic disease. The underlying pathogenesis is not fully understood but appears multifactorial. Multiple spinal cord protection strategies and monitoring techniques are currently utilized with variable results seen. The purpose of this review is to summarize important and recent findings related to cause, monitoring and impact of multiple spinal cord protection strategies. Recent Findings Recent data suggests collateral blood flow as the major determinant of spinal cord perfusion instead of individual intercostal vessels, potential role of transcutaneous near-infrared spectroscopy for monitoring of spinal cord perfusion and positive impact of implementing multimodal spinal cord protection strategies on reducing the risk of SCI. Summary SCI leading to paraplegia is a multifactorial complication that remains a major concern in complex aortic surgeries. Although there are no sufficient data to document the efficacy of spinal cord protection techniques individually, their effect on lowering the risk of SCI is most evident when used concomitantly using a multimodal approach that encompasses the perioperative and early postoperative period. Correspondence to Lovkesh Arora, MD, 200 Hawkins drive, 6JCP, Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA 52242-1079, USA. Tel: +1 319 384 6079; e-mail: Lovkesh-arora@uiowa.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Prehabilitation is better than cure

Purpose of review With a continuously growing number of older patients undergoing major surgical procedures, reliable parameters practicable in perioperative routine revealing those patients at risk are urgently needed. Recently, the concept of 'prehabilitation' with its key elements exercise, nutrition and psychological stress reduction especially in frail patients is attracting increasing attention. Recent findings Literature search revealed a huge amount of publications in particular within the last 12 months. Although a single definition of both frailty and prehabilitation is still to be made, various players in the perioperative setting obviously are becoming increasingly convinced about a possible benefit of the program – referring to different components and measures performed. Although physiologically advantages seem obvious, there is hardly any reliable data on clinical outcomes resulting from properly performed studies. This applies especially to octogenarians; thus those at risk for adverse events the concept originally addresses. Summary Identifying high-risk patients at the earliest possible stage and increasing their physiological reserve prior to surgery is a promising approach that seems to result in remarkable improvements for older patients. However, further studies on effectiveness in a highly heterogeneous population and agreement on a common concept are mandatory before a final judgement can be given. Correspondence to Simone Gurlit, MD, Department of Anesthesiology and operative Intensive Care, St. Franziskus-Hospital Muenster, Hohenzollernring 70, 48145 Muenster, Germany. Tel: +49 251 935 3936; fax: +49 251 935 4077; e-mails: simonegurlit@aol.com, simone.gurlit@sfh-muenster.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Delayed recovery following thoracic surgery: persistent issues and potential interventions

Purpose of review Lung and esophageal surgery remain a curative option for resectable cancers. However, despite advances in surgical and anesthesia practices, the inclusion of patients with comorbidities that would have previously not been offered curative resection presents additional concerns and challenges. Recent findings Perioperative complication rates remain high and prolonged and/or painful recovery are common. Further, many patients face a permanent decline in their functional status, which negatively affects their quality of life. Examination of the variables associated with high complications following thoracic surgery reveals patient, physician, and institutional factors in the forefront. Anesthesiologist training, Enhanced Recovery After Surgery protocols, and preparations to minimize "failure to rescue" when a complication does arise are key strategies to address adverse outcomes. Summary Delayed and complicated recovery after thoracic noncardiac surgery persist in current practice. This review analyzes the diverse factors that can impact complications and quality of life after lung surgery and the interventions that can help decrease length of stay and improve return to baseline conditions. Correspondence to Alessia Pedoto, MD FASA, Department of Anesthesiology and Critical Care Medicine, 1275 York Ave. Room M301, New York, NY 10065, USA. Tel: +1 212 639 6840; e-mail: pedotoa@mskcc.org Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Functional Microbiomics in Liver Transplantation: Identifying Novel Targets for Improving Allograft Outcomes

Gut dysbiosis, defined as a maladaptive gut microbial imbalance, has been demonstrated in patients with end-stage liver disease (ESLD), defined as a contributor to disease progression, and associated clinically with severity of disease and liver-related morbidity and mortality. Despite this well recognized phenomena in patients with ESLD, the impact of gut dysbiosis and its rate of recovery following liver transplantation (LT) remains incompletely understood. The mechanisms by which alterations in the gut microbiota impact allograft metabolism and immunity, both directly and indirectly, are multifactorial and reflect the complexity of the gut-liver axis. Importantly, while research has largely focused on quantitative and qualitative changes in gut microbial composition, changes in microbial functionality (in the presence or absence of compositional changes) are of critical importance. Therefore, in order to translate functional microbiomics into clinical practice, one must understand not only the compositional, but also, the functional changes associated with gut dysbiosis and its resolution post-LT. In this review, we will summarize critical advances in functional microbiomics in liver transplant recipients as they apply to immune-mediated allograft injury, posttransplant complications, and disease recurrence while highlighting potential areas for microbial-based therapeutics in liver transplant recipients. Corresponding Author: Michael Kriss, MD, 12700 E. 19th Ave., Campus Box B146, Aurora, CO 80045. Email: Michael.Kriss@ucdenver.edu. Office: 303-724-1030 Authorship Page: Authorship: Michael Kriss, MD – participated in writing of the manuscript, participated in revision and final review of the manuscript Elizabeth C Verna, MD, MS – participated in revision and final review of the manuscript Hugo R Rosen, MD – participated in revision and final review of the manuscript Catherine A Lozupone, PhD – participated in revision and final review of the manuscript Disclosures: The authors declare no conflicts of interest Funding (relative to work reviewed): Michael Kriss, MD – Supported by NIH/NCATS Colorado CTSA Grant Number UL1 TR002535. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. Elizabeth C Verna, MD, MS – Supported by NIH Grant Number K23 DK101827 Catherine A Lozupone, PhD – Supported by NIH Grant Numbers R01 DK104047, RO1 DK108366, and RO1 HL138639 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Development of a predictive model using endoscopic features for gastric cytomegalovirus infection in renal transplant patients

Background Cytomegalovirus (CMV) is a common viral pathogen in transplant patients that often targets the stomach. However, the endoscopic characteristics of gastric CMV infection are not well established. We aimed to develop a predictive model using endoscopic findings for gastric CMV infection in renal transplant patients. Methods A retrospective study of 287 kidney transplant recipients who underwent endoscopy with biopsy for suspected CMV infection from Jan. 2006 to Nov. 2015 at a tertiary referral hospital was performed. CMV infection was defined based on inclusion bodies in hematoxylin and eosin and immunohistochemical staining. Endoscopic and clinical parameters related with gastric CMV infection were selected by univariate analyses. Multivariate logistic regression was used to create a predictive model from β-coefficients. Results CMV was present in 107 (37.7%) of the 287 patients. Multivariate analysis found age (odds ratio (OR) 0.964, 95% confidence interval (CI) 0.938-0.99, p=0.008), erosions with surface exudate (OR 5.34, 95% CI 2.687-10.612, p

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Early diagnosis and treatment of subclinical ABMR is vital for improving clinical outcomes

No abstract available

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Dynamic Frailty Before Kidney Transplantation—Time of Measurement Matters

Background Frail kidney transplant (KT) recipients have higher risk of adverse post-KT outcomes. Yet, there is interest in measuring frailty at KT evaluation and then using this information for post-KT risk stratification. Given long wait times for KT, frailty may improve or worsen between evaluation and KT. Patterns, predictors, and post-KT adverse outcomes associated with these changes are unclear. Methods 569 adult KT candidates were enrolled in a cohort study of frailty (11/2009-09/2017) at evaluation and followed-up at KT. Patterns of frailty transitions were categorized as: 1) binary state change (frail/nonfrail); 2) 3-category state change (frail/intermediate/nonfrail); and 3) raw score change (-5 to 5). Adjusted Cox proportional hazard and logistic regression models were used to test whether patterns of frailty transitions were associated with adverse post-KT outcomes. Results Between evaluation and KT, 22.0% became more frail, while 24.4% became less frail. Black race (RRR=1.98, 95%CI:1.07-3.67) was associated with frail-to-nonfrail transition; diabetes (RRR=2.56, 95%CI:1.22-5.39) was associated with remaining stably frail. Candidates who became more frail between 3-category states (HR=2.27, 95%CI:1.11-4.65) or frailty scores (HR=2.36, 95%CI:1.12-4.99) had increased risk of post-KT mortality and had higher odds of length of stay (LOS) ≥2 weeks (3-category: OR=2.02, 95%CI:1.20-3.40; scores: OR=1.92, 95%CI:1.13-3.25). Conclusions Almost half of KT candidates experienced change in frailty between evaluation and KT, and those transitions were associated with mortality and longer LOS. Monitoring changes in frailty from evaluation to admission may improve post-KT risk stratification. *NMC and AD contributed equally to this manuscript. Contact Information: Nadia M. Chu, PhD, MPH, Department of Surgery 615, N. Wolfe St, Baltimore, MD 21205, (215) 200-5327 email: nchu8@jhu.edu. Alternate Corresponding Author: mara@jhu.edu. AUTHORSHIP Participated in data analysis: NMC, AD, HY; participated in research design: MMD, DLS; participated in writing of the paper NMC, AD; participated in performance of the research: MMD, DLS; participated in critical revision of the paper: NMC, AD, HY, CEH, JMGW, MMD, DLS; participated in approval of paper: NMC, MMD, DLS. STATEMENT OF COMPETING FINANCIAL INTERESTS Disclosures: None FUNDING This study was supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) grant numbers: K24DK101828 (PI: Segev) and K23DK115908 (PI: Garonzik Wang), as well as the National Institute on Aging (NIA) grant numbers: F32AG053025 (PI: Haugen), R01AG042504 (PI: Segev), K01AG043501 (PI: McAdams-DeMarco), and R01AG055781 (PI: McAdams-DeMarco). Mara A. McAdams-DeMarco was also supported by the Johns Hopkins University Claude D. Pepper Older Americans Independence Center (P30AG021334). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Changes in frailty status – some better, some worse

No abstract available

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Subclinical Antibody Mediated Rejection after Kidney Transplantation: Treatment Outcomes

Background Antibody-mediated rejection (ABMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical ABMR based on the donor-specific antibody (DSA) testing may result in better outcomes. Methods We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between 03/01/2013 and 12/31/2016. Patients were divided into three groups: clinical ABMR (n=118), subclinical ABMR (n=25), or no rejection on protocol biopsy (controls) (n=77). Results Both clinical and subclinical ABMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (p=ns). Mean follow-up after ABMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical ABMR groups, respectively (p

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Delta radiomic features improve prediction for lung cancer incidence: A nested case–control analysis of the National Lung Screening Trial

We demonstrated that combining delta radiomics with baseline radiomics generally improved the performance statistics to predict lung cancer incidence when compared to using only baseline radiomic features. We note inconsistent results in the performance statistics when we comparing overall models compared to models based on nodule size. As such, our findings suggest there is a trade‐off in terms of performance using nodule size‐specific models vs. an overall model.

Abstract

Background

Current guidelines for lung cancer screening increased a positive scan threshold to a 6 mm longest diameter. We extracted radiomic features from baseline and follow‐up screens and performed size‐specific analyses to predict lung cancer incidence using three nodule size classes (<6 mm [small], 6‐16 mm [intermediate], and ≥16 mm [large]).

Methods

We extracted 219 features from baseline (T0) nodules and 219 delta features which are the change from T0 to first follow‐up (T1). Nodules were identified for 160 incidence cases diagnosed with lung cancer at T1 or second follow‐up screen (T2) and for 307 nodule‐positive controls that had three consecutive positive screens not diagnosed as lung cancer. The cases and controls were split into training and test cohorts; classifier models were used to identify the most predictive features.

Results

The final models revealed modest improvements for baseline and delta features when compared to only baseline features. The AUROCs for small‐ and intermediate‐sized nodules were 0.83 (95% CI 0.76‐0.90) and 0.76 (95% CI 0.71‐0.81) for baseline‐only radiomic features, respectively, and 0.84 (95% CI 0.77‐0.90) and 0.84 (95% CI 0.80‐0.88) for baseline and delta features, respectively. When intermediate and large nodules were combined, the AUROC for baseline‐only features was 0.80 (95% CI 0.76‐0.84) compared with 0.86 (95% CI 0.83‐0.89) for baseline and delta features.

Conclusions

We found modest improvements in predicting lung cancer incidence by combining baseline and delta radiomics. Radiomics could be used to improve current size‐based screening guidelines.

https://ift.tt/2DWGSi8

Effect of supplementing chromium histidinate and picolinate complexes along with biotin on insulin sensitivity and related metabolic indices in rats fed a high‐fat diet

The effects of chromium histidinate (CrHis) and chromium picolinate (CrPic) complex along with biotin to a high‐fat diet (HFD) fed to rats on the insulin sensitivity and the anti‐obesity properties were investigated. We reported that biotin supplementation with chromium complexes, CrHis in particular, to a HFD pose to be a potential therapeutic feature for the treatment of insulin resistance.

Abstract

Scope

To investigate the effects of chromium histidinate (CrHis) and chromium picolinate (CrPic) complex along with biotin to a high‐fat diet (HFD) fed to rats on the insulin sensitivity and the anti‐obesity properties.

Methods

Forty‐two Sprague–Dawley male rats were divided into six groups. The rats were fed either (a): a standard diet (Control) or (b): a HFD or (c): a HFD with biotin (HFD+B) or (d): a combination of HFD and biotin along with CrPic (HFD + B + CrPic) or (e): a combination of HFD and biotin along with CrHis (HFD + B + CrHis) or (f): a combination of HFD and biotin along with CrHis and CrPic (HFD + B + CrHis + CrPic).

Results

Adding biotin with chromium to HFD improved the glucose, insulin, HOMA‐IR, leptin, lipid profile, with HFD+B+CrHis treatment being the most effective (p = 0.0001). Serum, liver, and brain tissue Cr concentrations increased upon Cr supplementations (p = 0.0001). Supplementing CrHis along with biotin to a HFD (HFD + B + CrHis) provided the greatest levels of GLUT‐1, GLUT‐3, PPAR‐γ, and IRS‐1, but the lowest level of NF‐κB in the brain and liver tissues.

Conclusion

Biotin supplementation with chromium complexes, CrHis in particular, to a HFD pose to be a potential therapeutic feature for the treatment of insulin resistance.

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Efficacy of Acupuncture for Treating Opioid Use Disorder in Adults: A Systematic Review and Meta-Analysis

Objectives. To assess the efficacy of acupuncture in treating opioid use disorder (OUD). Design. Systematic review and meta-analysis. Methods. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, ProQuest Dissertation and Theses, Allied and Complementary Medicine Database (AMED), Clinicaltrials.gov, and who.int/trialsearch were searched from inception to 23 December 2017. The methodological quality of selected studies and the quality of evidence for outcomes were assessed, respectively, by the Cochrane risk of bias assessment tool and the GRADE approach. Statistical analyses were conducted by RevMan 5.3. Results. A total of nine studies involving 1063 participants fulfilled the inclusion criteria. The results showed that acupuncture could be more beneficial than no treatment/sham acupuncture in terms of changes in craving for opioid (MD -2.18, 95% CI -3.10 to -1.26), insomnia (MD 2.31, 95% CI 1.97 to 2.65), and depression (SMD -1.50, 95% CI -1.85 to -1.15). In addition, these findings showed that, compared to sham electroacupuncture (EA), EA had differences in alleviating symptoms of craving (SMD -0.50, 95% CI -0.94 to -0.05) and depression (SMD -1.07, 95% CI -1.88 to -0.25) and compared to sham transcutaneous acupoint electrical stimulation (TEAS), TEAS had differences in alleviating symptoms of insomnia (MD 2.31, 95% CI 1.97 to 2.65) and anxiety (MD -1.26, 95% CI -1.60 to -0.92) compared to no treatment/sham TEAS. Conclusions. Acupuncture could be effective in treating OUD. Moreover, EA could effectively alleviate symptoms of craving for opioid and depression, and TEAS could be beneficial in improving symptoms of insomnia and anxiety. Nevertheless, the conclusions were limited due to the low-quality and small number of included studies. PROSPERO registration number is CRD42018085063.

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The Increase of Flavonoids in Pericarpium Citri Reticulatae (PCR) Induced by Fungi Promotes the Increase of Antioxidant Activity

There are thousands of traditional Chinese medicines in China, and they all have to be stored for a period of time for the reason of market price or other factors. But some traditional Chinese medicines especially need to be stored longer, and the clinical efficacy will be better. The cause and mechanism of this phenomenon have attracted much attention in recent years. In this study, we analyze the reason of "the longer storage period the better" of Pericarpium Citri Reticulatae (PCR); method of microscopic and molecular identification was used to identify the fungi separated and purified from PCR. The HPLC and UV spectrophotometry methods were used to determine the contents of flavonoids in PCR. The isolated fungi were inoculated into sterile samples to screen the fungi closely related to the change of flavonoids. The results indicate that the strain of Aspergillus niger could obviously promote the contents of flavonoids, and it could also increase the antioxidant effect of PCR. In conclusion, this study explains the reason of "the longer storage period the better" of PCR from the perspective of microbe, proving the beneficial effect of microorganism on the surface of PCR.

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Therapeutic Effect of Superficial Acupuncture in Treating Myofascial Pain of the Upper Trapezius Muscle: A Randomized Controlled Trial

The aim of this study was to compare the treatment efficacies of superficial acupuncture and traditional acupuncture on trigger points of the upper trapezius muscle. Forty people were recruited and randomly allocated to the traditional and superficial acupuncture groups. Each subject received two treatments per week in a four-week period. Outcomes were measured by visual analogue scale (VAS), the Northwick Park neck pain questionnaire scores (NPQ), and pressure pain threshold (PPT) assessments of trigger points. Data collected before the interventions were considered as baseline. Assessments were performed after the first treatment and at the end of the second and fourth weeks of treatment. Patients reported significant (p

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Apoptosis Effects of Dihydrokaempferol Isolated from Bauhinia championii on Synoviocytes

Bauhinia championii (Benth.) Benth. is a traditional medicinal plant used in China to treat rheumatoid arthritis (RA), especially in She ethnic minority group. This study focused on the active constituents from the rattan of B. championii (Benth.) Benth., which possess potential apoptosis effects. A conventional phytochemical separation method for the isolation of compounds from the ethyl acetate extract of B. championii was developed. The procedure involved extraction, liquid–liquid partitioning with ethyl acetate, and subsequent compound purification, respectively. Additionally, cell viability of dihydrokaempferol found abundantly in it was evaluated in vitro by MTS, and the antiapoptosis effect was evaluated by annexin V/PI staining (Flow Cytometry Analysis) and western blot. The results showed that nine flavonoids, and five other compounds, were isolated from the ethyl acetate extract of B. championii and were identified as β-sitosterol (1), 5,6,7,3',4',5'-hexamethoxyflavone (2), 3',4',5,7-tetrahydroxyflavone (3), 5,7,3',4',5'-pentamethoxyflavone (4), 4'-hydroxy-5,7,3',5'-pentamethoxyflavone (5), apigenin (6), liquiritigenin (7), 5, 7-dihydroxylcoumarin (8), 3',4',5,7, -pentamethoxyflavone (9), n-octadecanoate (10), lupine ketone (11), dibutylphthalate (12), dihydrokaempferol (13), and 5,7,3′,5′-tetrahydroxy-6-methylflavanone (14). Among these compounds, 5-14 were isolated for the first time from B. championii. In addition, apoptosis effects of abundant dihydrokaempferol were evaluated in vitro. Dihydrokaempferol exhibited inhibitory effects on the proliferation of synoviocytes. Furthermore, dihydrokaempferol promoted Bax and Bad expression, as well as the cleavage of caspase-9, caspase-3, and PARP. Meanwhile, it inhibited Bcl-2 and Bcl-xL expression. These findings indicate that dihydrokaempferol isolated from the ethyl acetate extract of B. championii effectively promotes apoptosis, which is an important process through suppression of apoptotic activity. The results are encouraging for further studies on the use of B. championii in the treatment of RA.

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Editorial Board

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Planctomycetes in boreal and subarctic wetlands: diversity patterns and potential ecological functions

ABSTRACT

Members of the phylum Planctomycetes are common inhabitants of boreal Sphagnum peat bogs and lichen-dominated tundra wetlands. These bacteria colonize both oxic and anoxic peat layers and reach the population size of 10⁷ cells per gram of wet peat. The 16S rRNA gene sequences from planctomycetes comprise 5%–22% of total 16S rRNA gene reads retrieved from peat samples. Most abundant peat-inhabiting planctomycetes affiliate with the families Isosphaeraceae and Gemmataceae, and with as-yet-uncultured Phycisphaera-related group WD2101. The use of metatranscriptomics to assess the functional role of planctomycetes in peatlands suggested the presence of versatile hydrolytic capabilities in these bacteria. This evidence was further confirmed by the analysis of genome-encoded capabilities of isolates from wetlands. Large (up to 12 Mbp) genomes of planctomycetes encode wide repertoires of carbohydrate-active enzymes including many unclassified putative glycoside hydrolases, which suggests the presence of extremely high glycolytic potential in these bacteria. Experimental tests confirmed their ability to grow on xylan, pectin, starch, lichenan, cellulose, chitin and polysaccharides of microbial origin. These results provide an insight into the ecological roles of peat-inhabiting planctomycetes and suggest their participation in degradation of plant-derived polymers, exoskeletons of peat-inhabiting arthropods as well as exopolysaccharides produced by other bacteria.

https://ift.tt/2U45iMe

Burden of Sickle Cell Disease in Ghana: The Korle-Bu Experience

In Africa, sickle cell disease (SCD) is a major public health problem with over 200,000 babies born per year. In Ghana, approximately 15,000 (2%) of Ghanaian newborns are diagnosed with SCD annually. A retrospective review of medical records of all SCD patients aged 13 years and above, who presented to the sickle cell clinic at Ghana Institute of Clinical Genetics (GICG), Korle-Bu, from 1st January 2013 to 31st December 2014, was carried out, using a data abstraction instrument to document their phenotypes, demographics, attendance/clinic visits, pattern of attendance, and common complications seen. During the period under review 5,451 patients were seen at the GICG, with 20,788 clinic visits. The phenotypes were HbSS (55.7%) and HbSC (39.6%) with other sickle cell phenotypes (4.7%). Out of the 20,788 clinic visits, outpatient visits were 15,802 (76%), and urgent care visits were 4,986 (24%), out of which 128 (2.6%) patients were admitted to the Teaching Hospital for further management of their acute complications. There were 904 patient referrals (out of 5,451 patients) for specialist care; the 3 specialties that had the most referrals were Obstetrics and Gynaecology (168 patients), Orthopaedics (150 patients), and Ophthalmology (143 patients). In 2014, complications seen at KBTH included 53 patients with avascular necrosis (AVN) and 61 patients with chronic leg ulcers. Our centre has a large number of patients living with sickle cell disease. From our experience, early recognition and referral of sickle cell related complications can reduce morbidity and mortality associated with this disease. A multidisciplinary approach to care of SCD patients is therefore important.

https://ift.tt/2BLF0HA

Organizational and Technological Aspects of a Platform for Collective Food Awareness

Can Internet-of-food technologies foster collective food awareness within a food consumer community? The paper contributes to answer this question in a fourfold aspect. Firstly, we model a cooperative process for generating and sharing reliable food information that is derived from food instrumental measurements performed by consumers via smart food things. Secondly, we outline the functional architecture of a platform capable to support such a process and to let a consumer community share reliable food information. Thirdly, we identify main entities and their attributes necessary to model the contextualized interaction between a consumer and the platform. Lastly, we review articles reviewing technologies capable of acquiring and quantifying food characteristics for food performances assessment. The purpose is to give an insight into current research directions on technologies employable in a platform for collective food awareness.

https://ift.tt/2E6YU1T

Incorporating Accessibility Elements to the Software Engineering Process

The expansion of web is a phenomenon that brings several challenges in different segments of the society. Accessibility is one of these challenges and it is related to the digital inclusion and social welfare of the population. Thus, making accessible software available can contribute to solution of problems that currently exist in relation to access to information and services by all citizens. The purpose of this article is to present an approach that integrates accessibility to the Software Engineering process. We also present the Acero tool, which provides computational support to the proposed approach. Results were evaluated and we concluded that the use of the proposal reached the objectives, supporting different stages of the development process and contributing to obtain accessible software products.

https://ift.tt/2SnHuBf

Corrigendum to “Effects of Electroacupuncture on Methamphetamine-Induced Behavioral Changes in Mice”

https://ift.tt/2Ub455U

Pharmacological Effect of Quercetin in Hypertension and Its Potential Application in Pregnancy-Induced Hypertension: Review of In Vitro, In Vivo, and Clinical Studies

Since improving maternal and child health is a public health priority worldwide, the main aim of treatment of hypertension in pregnant women is to prevent complications during pregnancy, labor, and postpartum. In consequence, much attention is paid to the use of antihypertensive drugs that can be used safely during pregnancy. Several side effects of methyldopa, which is currently the most commonly used antihypertensive drug in pregnant women, mean that the search for an effective and safe alternative still continues. Flavonoid compounds present in medicinal plants, vegetables, and fruits may be a promising source of new drugs. In this aspect, quercetin, a well-known flavonoid due to its antihypertensive action, may be considered a prototype for safe antihypertensive drugs. This review focuses on the selective activity of quercetin. Based on recent studies, a few problems were discussed, including (1) pathology of pregnancy-induced hypertension; (2) search for new pharmacological treatments of pregnancy-induced hypertension; (3) issues with the use of herbal extracts during pregnancy; (4) flavonoids as natural active chemical compounds; (5) quercetin: its action during pregnancy, in vitro and in vivo pharmacological activities, clinical trials, and meta-analysis; (6) quercetin intake during pregnancy; (7) other natural compounds tested during pregnancy; (8) potential problems with the use of quercetin; (9) safety profile of quercetin. Various studies have shown a beneficial effect of quercetin on vascular endothelial function and its antioxidative and anti-inflammatory activity on cellular and tissue level. It is known that in animal models quercetin affects positively the development of embryo, fetus, and placenta. Because this flavonoid did not have teratogenic and abortive effect, it is generally recognized as safe. For this reason it should be appreciated and studied in the aspect of its potential use in the prevention and treatment of pregnancy-induced hypertension among women in this risk group.

https://ift.tt/2AGvBPF

The Association of Radial Artery Pulse Wave Variables with the Pulse Wave Velocity and Echocardiographic Parameters in Hypertension

This study aims at exploring the cardiovascular pathophysiological mechanism of TCM (traditional Chinese medicine) pulse by detecting the correlation between radial artery pulse wave variables and pulse wave velocity/echocardiographic parameters. Two hundred Chinese subjects were enrolled in this study, which were grouped into health control group, hypertension group, and hypertensive heart disease group. Physical data obtained in this study contained TCM pulse images at "Guan" position of the left hand, pulse wave velocity, and echocardiographic parameters. Linear and stepwise regression analysis was performed to assess the association of radial artery pulse wave variables with pulse wave velocity and echocardiographic parameters in the total population and in each different group. After adjusting for related confounding factors, decrease of t1, t5 and increase of h1, h3/h1 were statistically associated with arterial stiffness in the total population (P

https://ift.tt/2U5luN1

Corrigendum to “Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats”

https://ift.tt/2AD1GaU

Corrigendum to “Astilbin from Smilax glabra Roxb. Attenuates Inflammatory Responses in Complete Freund’s Adjuvant-Induced Arthritis Rats”

https://ift.tt/2U45eMp

Corrigendum to “A Randomized Controlled Trial of Chinese Patent Medicine Xiao’er Biantong Granules in the Treatment of Functional Constipation in Children”

https://ift.tt/2AHzzYo

Treatment of multiple system atrophy - the past, present and future.

Related Articles

Treatment of multiple system atrophy - the past, present and future.

Am J Clin Exp Immunol. 2018;7(5):88-94

Authors: Yu H, Yuan X, Liu L, Wang T, Gong D

Abstract
Multiple system atrophy is a sporadic progressive degenerative disease which is characterized by multiple central nervous systems involved. So far, there is no effective medicine to cure MSA. The main research direction of treatment includes immunization transplantation and cytotherapy. Human umbilical cord blood is the residue of blood in the placenta and umbilical cord after fetal delivery. It is the most abundant cell bank and its usage is not limited to treat hematological diseases. The researches about hUCB-MNC treatment on MSA are increasing gradually. The potential of other MSC is also discussed. Lateral atlanto-occipital space puncture is an ingenious way created by Professor Dianrong Gong. More than 30 cases of MSA have been treated by this method with fine clinical effect and without serious complications. It indicates that stem cells treatment is a valid method for refractory nerve system diseases.

PMID: 30498625 [PubMed]

https://ift.tt/2AE2TPy

Tumor-infiltrating regulatory T cells: origins and features.

Related Articles

Tumor-infiltrating regulatory T cells: origins and features.

Am J Clin Exp Immunol. 2018;7(5):81-87

Authors: Deng G

Abstract
Tumor cells evolve multiple sophisticated mechanisms to escape immune surveillance, one of which is to establish tolerogenic microenvironment by recruiting certain immune suppressive cells such as regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). Tregs are subpopulation of CD4+ T cells, which specialize in suppressing immune responses and preventing autoimmune damage to collateral tissue. Emerging evidence suggests that Treg cell number increases in various types of cancer, which correlates with tumor grade and poor patient prognosis. This review will focus on discussion of the origins and features of tumor-infiltrating Treg cells. Ultimately, these features may provide insight into potential therapeutic intervention by targeting Treg cells to invigorate immune response against tumor.

PMID: 30498624 [PubMed]

https://ift.tt/2AEJLRb

IgG Antibodies to GlcNAcβ and Asialo-GM2 (GA2) Glycans as Potential Markers of Liver Damage in Chronic Hepatitis C and the Efficacy of Antiviral Treatment

Total serum IgG level is a surrogate marker of hepatitis C (HC) severity. Antibodies (Abs) to microbial glycans could be markers of HC severity caused by the translocation of microbial products. The level of anti-glycan (AG) Abs was analysed in serum samples of patients () with chronic HC in ELISA using fourteen synthetic glycans present in microbes and adhesins to evaluate the association of Abs with clinical parameters and the efficacy of antiviral treatment. The anti-GlcNAcβ IgG level was significantly higher in patients with fibrosis () and severe portal inflammation () regardless of other clinical parameters. The ROC curve analysis showed sensitivity of 0.59, specificity of 0.84, and AUC of 0.71 in discriminating F0 from F1–4 (HCV genotype-1b-infected patients). The level of anti-GA2 Abs before Peg-IFN/RBV treatment was significantly higher in nonsustained viral response (non-SVR) to treatment than in SVR (). ROC analysis showed sensitivity of 0.62, specificity of 0.70, and AUC of 64. Correlations of AG Abs to clinical parameters were found. The quantification of anti-GlcNAcβ Abs deserves attention in assessment of the hepatic damage while anti-GA2 Abs may be a sign of immune response related to the antiviral treatment.

https://ift.tt/2G2PpCy

Corrigendum to “The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients with Cardiovascular Diseases”

https://ift.tt/2ri7uCC

Correlation of Triiodothyronine Level with In-Hospital Cardiac Function and Long-Term Prognosis in Patients with Acute Myocardial Infarction

Objective. The pathophysiologic mechanism of how thyroid function is related to the development and prognosis of acute myocardial infarction (AMI) remains under explored, and there has been a lack of clinical investigations. In this study, we investigate the relationship between triiodothyronine (T3) level and cardiac ejection fraction (EF) as well as probrain natriuretic peptide (NT-proBNP) on admission and subsequent prognosis in AMI patients. Methods. We measured admission thyroid function, NT-proBNP, and EF by echocardiography in 345 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between T3 level and EF as well as NT-proBNP. Major adverse cardiovascular events (MACE), including new-onset myocardial infarction, acute heart failure, and cardiac death, were documented during the follow-up. 248 participants were separated into three groups based on T3 and free triiodothyronine (FT3) levels for survival analysis during a 2-year follow-up. Results. 345 patients diagnosed with AMI were included in the initial observational analysis. 248 AMI patients were included in the follow-up survival analysis. The T3 levels were found to be significantly positively correlated with EF (,) and negatively correlated with admission NT-proBNP levels (,), which is the same with the correlation between FT3 and EF (,) and admission NT-proBNP levels (,). Kaplan-Meier survival analysis revealed no significant difference with regard to different T3 or FT3 levels at the end of follow-up. Conclusions. T3 and FT3 levels are moderately positively correlated with cardiac function on admission in AMI patients but did not predict a long-time survival rate. Further studies are needed to explain whether longer-term follow-up would further identify the prognosis effect of T3 on MACE and all-cause mortality.

https://ift.tt/2G2Pnuq

Nomogram Based on Systemic Immune-Inflammation Index to Predict Overall Survival in Gastric Cancer Patients

Background. The systemic immune-inflammation index (SII), based on peripheral lymphocytes, neutrophils, and platelet count, has been used as a prognostic marker for several tumors. However, use of the SII has not been reported for gastric cancer. Methods. We evaluated the prognostic value of the SII in primary and validation cohorts. We also established an effective prognostic nomogram for gastric cancer based on R language. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C index) and a calibration curve and were compared with TNM classifications. Results. The Kaplan-Meier survival analysis results showed that the high SII was associated with poor prognosis of gastric cancer patients in the primary and validation cohorts. SII proved to be related to tumor location, histological grade, tumor size, TNM stage, and perineural infiltration in patients with gastric cancer and was an independent prognostic factor for patients with gastric cancer. SII has a better predictive ability than other existing prognostic indexes based on inflammation, such as NLR, PLR, and MLR. The nomogram established can accurately predict the 3- and 5-year survival rates of patients with gastric cancer after operation, and its accuracy is significantly higher than that of the 8th edition of the AJCC staging system. Conclusion. SII can independently predict the overall survival of patients with gastric cancer after operation, which is superior to the existing systemic inflammatory indexes. The prognostic nomogram based on SII is a reliable model for predicting the postoperative survival of patients with gastric cancer.

https://ift.tt/2rbxgZg

Genotype Diversity of Newcastle Disease Virus in Nigeria: Disease Control Challenges and Future Outlook

Newcastle disease (ND) is one of the most important avian diseases with considerable threat to the productivity of poultry all over the world. The disease is associated with severe respiratory, gastrointestinal, and neurological lesions in chicken leading to high mortality and several other production related losses. The aetiology of the disease is an avian paramyxovirus type-1 or Newcastle disease virus (NDV), whose isolates are serologically grouped into a single serotype but genetically classified into a total of 19 genotypes, owing to the continuous emergence and evolution of the virus. In Nigeria, molecular characterization of NDV is generally very scanty and majorly focuses on the amplification of the partial F gene for genotype assignment. However, with the introduction of the most objective NDV genotyping criteria which utilize complete fusion protein coding sequences in phylogenetic taxonomy, the enormous genetic diversity of the virus in Nigeria became very conspicuous. In this review, we examine the current ecological distribution of various NDV genotypes in Nigeria based on the available complete fusion protein nucleotide sequences (1662 bp) in the NCBI database. We then discuss the challenges of ND control as a result of the wide genetic distance between the currently circulating NDV isolates and the commonest vaccines used to combat the disease in the country. Finally, we suggest future directions in the war against the economically devastating ND in Nigeria.

https://ift.tt/2RtkFvY

Investigation of optimal physical parameters for precise proton irradiation of orthotopic tumors in small animals

The emergence of preclinical proton irradiation platforms dedicated to radiobiological studies drives the development of small-animal models, mimicking clinical therapy conditions. Targeted irradiations of small volumes are conditioned by the proton beam physical properties. Based on available proton beam data and Geant4 simulations, the optimal features to correctly deliver the prescribed physical dose in small-animal tumors were determined. In particular cases of millimetric tumors, low energy protons are better suited than protons > 50 MeV.

https://ift.tt/2G23tfY

Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery

The effects of smoking on HPV-related oropharyngeal outcomes are not well defined. This retrospective review defines the effects of smoking on patients treated with radiation or surgery.

https://ift.tt/2reDqHZ

Long term follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): A randomized phase II study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage I peripheral non-small cell lung cancer

The final result of XXXX, a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction (arm 1) versus 48 Gy in 4 fractions (arm 2), was that 34 Gy emerged as the least toxic yet equally efficacious regimen. Long-term follow up results show no change by arm in toxicity rates or tumor control with time for similar median survivals, supporting the study's original conclusions.

https://ift.tt/2G23vo6

Detection of human papillomavirus 67 single infection in high‐grade cervical lesions: Case report and review of literature

https://ift.tt/2AF2jRB

Aspergillus thyroiditis: In an immunocompromised young adult

https://ift.tt/2Ub0pRE

Metastatic clear cell renal carcinoma to the auricular region disguised as a vascular thrombus: Case report

In about 25‐30% of patients with primary renal cell carcinoma, metastasis is not uncommon and usually does not give rise to difficulties in diagnosis. However, its presentation as a subcutaneous mass following an elapse of several years after the initial diagnosis is not only uncommon but may be also mistaken for a thrombus in imaging studies due to its common high vascularization. We present here a case of a 70‐year‐old woman with an oncologic history of renal cell carcinoma who noticed after five years a mass in the auricular region radiologically suggestive of a vascular thrombus. Fine‐needle aspiration cytology showed malignant epithelial cells compatible with metastasis of renal clear cell carcinoma, supported by immunohistochemistry performed on the cell block. This rather uncommon presentation and precise diagnosis by fine‐needle aspiration prompted us to report the case, emphasizing the role of cytopathology as a useful, fast and minimally invasive method for clarifying the neoplastic nature of highly vascularized lesions.

https://ift.tt/2AGuFed

Fine‐needle aspiration cytology of non‐small cell lung carcinoma: A paradigm shift

Lung carcinoma is one of the commonest causes of cancer related death. Fine‐needle aspiration cytology (FNAC) is a well‐established technique in the diagnosis of various malignant tumors. FNAC is now an important technique in classifying lung carcinomas and also detecting salient mutational changes in lung carcinomas. The judicious use of the various immunological markers such as TTF‐1, p40, CK 5/6, CK 7 and Napsin may help in sub‐classification of non‐small cell lung carcinomas (NSCLC). The mutational changes in epidermal growth factor receptor (EGFR) and ALK genes are needed in targeted therapy of adenocarcinoma of lung. With the help of immunocytochemistry, polymerase chain receptor, fluorescent in situ hybridization and next generation sequencing, one can detect various mutational changes in NSCLC. In this review article, we have discussed the role of cytology and other ancillary techniques to classify lung carcinomas. The important mutational changes in lung carcinoma for targeted therapy have also been discussed in detail.

https://ift.tt/2U3l4Xz

Presence of eosinophilic intracytoplasmic inclusions diagnosed by fine needle aspiration cytology in perivascular epithelioid cell tumor (PEComa) arising from the cecum

https://ift.tt/2AKsQNs

Thyroid nodule size calculated using ultrasound and gross pathology as predictors of cancer: A 23‐year retrospective study

Background

Thyroid nodules are very common. Ultrasound (US) and fine needle aspiration (FNA) are both integral in cancer screening. This study investigated the concordance between thyroid nodule sizes measured by US and gross pathologic examination and their relationship with malignancy.

Methods

A retrospective design was used to select consecutive patients with proven carcinoma of the thyroid. The number and maximum diameter of nodules, rates and types of malignancy, as well as predictors of malignancy were determined.

Results

The 10 944 patients examined had 15 283 thyroid nodules, 44.6% of which were malignant. Of the 4449 nodules sampled by FNA and the 8748 not sampled by FNA, 76.5% and 30.5% were malignant, respectively. The sensitivity, specificity, positive and negative predictive values (NPVs), and overall accuracy of FNA based on final pathology were 97.9%, 96.3%, 98.8%, 93.5%, and 97.5%, respectively. Nodule sizes determined by US were comparable with most nodules having either the same size range (n = 2959, 77.7%) or differing only by one size range (n = 770, 20.5%).

Conclusions

Thyroid nodule size is inversely related to malignancy risk, as larger nodules have lower malignancy rates. Nodule size estimated by US shows relatively good correlation with final pathologic size. However, thyroid nodules should undergo FNA regardless of size. If the FNA is not benign, nodule size should influence therapeutic decision making.

https://ift.tt/2U63sdz

Standardized terminology systems in cytopathology

Abstract

There has been increasing pressure for systemization in cytopathology. Lack of uniformity in categorization, variation in opinion based regional practice, and technologic advancement have created an environment disposed toward creation of more consistent evidence‐based approaches to diagnostic problems. This review provides an overview of the major standardized terminology systems in cytology, with historical perspectives and commentary on current uses of these systems. These systems now include gynecologic, thyroid, pancreaticobiliary, urinary, salivary gland, and breast cytology. We summarize major classification systems supported by national and international professional organizations, outlining the structure and goals of each system. Specific benefits and potential pitfalls in the implementation of each system are given. Finally, we address potential criticisms of standardized terminology systems and proposed future directions to continue the evolution of standardized terminology to improve clinical practice.

https://ift.tt/2AFs7Ni

Appendiceal‐tie syndrome: acute appendicitis causing mechanical small bowel obstruction managed laparoscopically

https://ift.tt/2DZJnjR

Uncommon splenic mass with a distinctive appearance

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Validation of data submitted by the treating surgeon in the Victorian Audit of Surgical Mortality

Background

The Victorian Audit of Surgical Mortality (VASM) seeks to peer review all deaths associated with surgical care in Victoria, Australia. The effectiveness of the VASM as an educational and quality improvement tool is dependent on the accuracy of source data it receives. We aimed to examine the accuracy and quality of source data provided by the treating surgeon for peer review, and the inter‐rater concordance level between the external validator findings and the treating surgeon.

Methods

Of the 629 cases that completed the VASM audit second‐line peer review process over a 4‐year period (from 1 July 2012 to 30 June 2016), a total of 32 (5%) were randomly selected for the external validation process. The blinded external validator was impartial to the VASM audit, and was provided only de‐identified patient medical records. The analysis for the checked and validated data points and their concordance was determined using Gwet's agreement coefficient, which provides a stable inter‐rater reliability coefficient not affected by prevalence and marginal probability.

Results

The inter‐rater concordance analysis suggested that there is a high level of agreement (82.9% overall) between the treating surgeon and external validator. The use of thromboembolism deterrent stockings was the only variable where agreement was poor (52.4%) with a Gwet score of 0.10 (−0.40 to 0.60).

Conclusion

The inter‐rater concordance analysis results support the validity of the VASM process, which is dependent on the accuracy of data submitted by the treating surgeon.

https://ift.tt/2DZJmMP

Inner ear and retrocochlear pathology on magnetic resonance imaging for sudden and progressive asymmetrical sensorineural hearing loss

Background

In sudden and asymmetrical progressive sensorineural hearing loss (SNHL), magnetic resonance imaging (MRI) is required to evaluate retrocochlear pathology and, with recent advances in MRI techniques, inner ear pathology. Given the limited literature regarding inner ear pathology associated with SNHL, we aimed to assess the incidence of retrocochlear and inner ear pathology, and congenital malformation on MRI in sudden SNHL (SSNHL) and progressive SNHL.

Methods

A total of 987 acoustic neuroma (AN) protocol MRI internal acoustic meatus studies performed at our institution to investigate SNHL between January 2013 and December 2015 inclusive were identified. Following categorization for indication of SSNHL versus progressive asymmetrical SNHL, MRIs with retrocochlear or inner ear abnormality, congenital malformation or other otology‐related abnormality were identified, and further data were collected for these patients including patient demographics, associated symptomatology, management and outcomes.

Results

In SSNHL, aetiological abnormality on MRI was identified for 6.9% patients with AN present on 4% overall. 3.2% of MRIs for progressive asymmetrical SNHL identified a causative lesion with 2.3% of scans overall diagnosing AN. The incidence of congenital inner ear malformation on MRI in the setting of SSNHL and progressive asymmetrical SNHL are 1.7% and 0.6%, respectively.

Conclusion

This is the first retrospective study of inner ear MRI abnormalities in both SSNHL and progressive asymmetrical SNHL in Australia and one of the largest cohorts published in the literature to date. MRI must be performed in the setting of SNHL to ensure aforementioned and rarer causative lesions are identified.

https://ift.tt/2Qro4y8

Primary omental torsion

https://ift.tt/2DZJc8b

Rare presentation of a Bochdalek hernia in adulthood with incarcerated splenic flexure of the colon mimicking diverticulitis: a report and review

https://ift.tt/2DZJlbJ

Comparison of outcomes between hip fracture patients with concurrent upper limb injuries and patients with an isolated hip fracture

Background

Concurrent upper limb injuries can occur with hip fractures, and its incidence and effect on outcomes are unclear. The objective of this study was to review the number and types of upper limb injuries sustained by patients with hip fractures, and investigate how acute hospital stay, rehabilitation and patient outcomes are affected.

Methods

A retrospective study was performed on 820 patients with traumatic fracture of the hip over the age of 50. We reviewed the patients with concurrent upper limb injuries and compared patient outcomes – including mortality, acute length of stay in the orthopaedic ward, rehabilitation outcomes and rehabilitation length of stay.

Results

Thirty‐four patients (4.1%) with a hip fracture had a concurrent upper limb injury. Patients with and without concurrent upper limb injuries had similar acute length of stays on the orthopaedic ward (mean 5.2 versus 5.5 days, P = 0.4), and no significant difference in mortality rates at time of discharge (0% versus 3.8%, P = 0.4) and at 30 days (2.9% versus 9.1%, P = 0.2). However, they also required significantly longer rehabilitation (mean 34.6 versus 19.9 days, P = 0.009) even after other demographic factors including upper limb injury, older age and dementia were taken into consideration (multivariate linear model: concurrent upper limb injury, P = 0.0003; older age, P = 0.05; dementia, P = 0.09).

Conclusion

A concurrent upper limb injury is infrequent in the hip fracture population. Overall, these patients were previously higher functioning than the average hip fracture patient and required longer stays in inpatient rehabilitation than patients with isolated hip fractures.

https://ift.tt/2Qs1tBw

Fatal flaws in clinical decision making

Background

Clinical decision making is a core competency of surgical practice, involving a continuous and evolving process of data interpretation and evaluation. The aim of this article is twofold. First, to recognize patient deaths where a clinical incident arose following unsatisfactory clinical decision making, determining where in the clinical decision‐making process each failure occurred. Second, to discuss and explore individual incidents to provide lessons from which the surgical community can learn.

Methods

Using the Australian and New Zealand Audit of Surgical Mortality database, all deaths from 1 January 2015 to 31 December 2015 were analysed. All deaths in which the surgeon or assessor identified an aspect of patient management that was inadequate were recognized. Clinical incidents deemed by the assessor to be an area of concern or an adverse event were individually reviewed to determine if a clinical decision‐making incident (CDMI) occurred. CDMIs were categorized into various themes depending on the nature of the incident.

Results

A total of 3422 fully audited deaths occurred throughout the study period; from these cases, 226 individual CDMIs were identified. Decision to operate was the most commonly identified CDMI (n = 99, 43.8%), followed by diagnostic error (n = 49, 21.7%). The least common CDMI identified was inadequate post‐operative assessment (n = 14, 6.2%).

Conclusion

This paper demonstrates thought‐provoking examples of clinical decision‐making failure implicated in patient death. Clinical decision‐making failures most commonly occur around the decision to operate with increased discussion of complex cases possibly required. Further CDMI evaluation should be considered to complement more traditional methods of surgical mortality evaluation.

https://ift.tt/2DZJk7F

Mesenteric Meckel's diverticulum: an intra‐abdominal surprise

https://ift.tt/2QxF060

Strategy for discriminating cholesterol and premalignancy in polypoid lesions of the gallbladder: a single‐centre, retrospective cohort study

This study aimed to develop a strategy to discriminate cholesterol and premalignancy in polypoid lesions of the gallbladder. In the case of patients aged ≥50 years with single asymptomatic polyp, cholecystectomy was recommended if the polyp presented growth at a rate above 3–4 mm within 6 months.

Background

The present study aimed to assess the risk factors of cholesterol and premalignancy in polypoid lesions of the gallbladder (PLGs) and to establish an appropriate treatment strategy.

Methods

Data from patients who underwent cholecystectomy at the First Affiliated Hospital, School of Medicine, Zhejiang University, between January 2011 and July 2017, were collected retrospectively.

Results

A total of 1561 patients were included in the present study. The cohort comprised of 636 (40.7%) males and 925 (59.3%) females, with a mean age of 49.5 (range 16–88) years; 65.6% (1024/1561) demonstrated cholesterol lesions in this cohort, among which cholesterol polyps accounted for 81.0%. Age younger than 50 years and multiple number of polyps were found to be independent predictive variables for cholesterol lesions (odds ratio (OR) 3.461, 95% confidence interval (CI) 2.058–5.820, P < 0.001 and OR 3.321, 95% CI 1.988–5.547, P < 0.001, respectively). The presence of polyp growth was associated with premalignancy (OR 5.366, 95% CI 1.466–19.637, P = 0.011), and the presence of clinical symptoms indicated benign non‐cholesterol lesions (OR 0.368, 95% CI 0.153–0.885, P = 0.026).

Conclusion

In the case of patients ≥50 years old with single asymptomatic polyp, cholecystectomy was recommended if the polyp presented growth at a rate above 3–4 mm within 6 months. If not, trimonthly ultrasound follow up was recommended, and clinicians should carefully assess the risk factors for premalignancy in PLGs.

https://ift.tt/2DZJgor

Pancreaticoduodenectomy with right gastric vessels preservation: impact on intraoperative and postoperative outcomes

Background

Sympathetic denervation of the antropyloric area combined with relative devascularization from division of the right gastric vessels (RGV) during pancreaticoduodenectomy (PD) could predispose to delayed gastric emptying (DGE). Therefore, some authors advocated for RGV preservation (RGVP), where feasibility and utility for the prevention of post‐operative DGE have never been investigated.

Methods

From 2011 to 2014, patients who underwent classic Whipple PD (CWPD, n = 34), standard pylorus‐preserving PD (PPPD, n = 44) or PPPD with RGVP (n = 22) were retrospectively analysed.

Results

RGVP was not possible in 12% of the cases because of an intraoperative injury of the RGV. There was no difference between CWPD, standard PPPD and PPPD with RGVP in terms of intraoperative blood loss, operative time, number of lymph node harvested and resection margins. Post‐operative morbidity and mortality were comparable between the three groups, including rate (27%, 34% and 32%, P = 0.77) and severity of DGE, delay in removing nasogastric tube and use of prokinetics. Hospital stay was similar in all the compared groups.

Conclusion

This is the first study comparing post‐operative outcomes after PPPD with RGVP, standard PPPD and CWPD. Although feasible and safe, RGVP during PPPD appeared to offer no obvious clinical benefit in terms of preventing post‐operative complications, especially DGE.

https://ift.tt/2Qus0y2

Bile duct resection for eosinophilic cholangitis

https://ift.tt/2DVkbL9

Glove change to reduce the risk of surgical site infection or prosthetic joint infection in arthroplasty surgeries: a systematic review

Background

Microbiological contamination of surgical gloves occurs during surgery, which may warrant glove change during orthopaedic surgeries. However, no systematic review of this topic has previously been published. Therefore, this review evaluated whether changing gloves during arthroplasty surgeries reduces the risk of surgical site infection/prosthetic joint infection (SSI/PJI) and the optimal frequency of glove change.

Methods

Search terms such as surgical gloves, surgical site infections, prosthesis‐related infections, arthroplasty were used, including Medical Subject Headings terms. Of the 89 articles screened, 12 articles were included for qualitative synthesis.

Results

No studies measured the direct effect of glove change on PJI rate. Therefore, microbiological contamination and perforation rate of gloves were used as surrogate outcomes. Eight studies evaluated microbiological contamination of surgical gloves, with rates ranging from 3.4 to 30%. Five contamination studies recommended changing gloves after draping and before handling implants. One randomized controlled trial also recommended changing gloves at least once an hour regardless of surgical stages. Five studies recommended changing gloves to prevent perforation, with recommendations ranging from 20 to 90 min. Furthermore, one study advised change of gloves after resection of bone and before implantation.

Conclusion

As microbiological contamination rates of gloves increase with duration of surgery, glove changes are recommended at least once per hour. Furthermore, gloves should be changed after draping, before handling implants and if visible perforation is seen to reduce contamination. Due to the lack of studies with SSI/PJI as primary outcomes, we cannot draw a definitive conclusion regarding the effectiveness of changing gloves in reducing the risk of SSI/PJI in arthroplasty.

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Neoadjuvant therapy in rectal cancer: how are we choosing?

Background

Neoadjuvant therapy has revolutionized the management of rectal cancer; however, there is a need to examine the factors driving neoadjuvant treatment allocation. This study aimed to describe patterns of treatment allocation for patients with rectal cancer at our institution and identify predictors for receiving neoadjuvant therapy, and for choice of short‐ or long‐course therapy.

Methods

A retrospective review of a prospectively maintained database of 122 patients undergoing surgical resection for rectal cancer with curative intent, between 1 November 2012 and 31 October 2017. Univariate and multivariate analyses were performed to identify factors that determined which patients received neoadjuvant therapy, and whether it was short or long course.

Results

Eighty‐six patients (70%) received neoadjuvant therapy. Independent predictors for receiving neoadjuvant therapy were T3‐4 tumours (P < 0.001), node‐positive disease (P = 0.005) and mid (P = 0.045) or low rectal cancers (P < 0.001). Of those receiving neoadjuvant therapy, 38 (44%) received short course and 48 (56%) received long course. Node‐positive disease was the only predictor for receiving long rather than short‐course neoadjuvant therapy (P = 0.002). Overall, these factors predicted 76% of neoadjuvant treatment allocation. Our predictor model identified important areas of variance in our decision‐making.

Conclusion

Utilizing the identified factors, it appears that consistent decisions regarding neoadjuvant therapy are being made the majority of the time. These decisions are largely driven by T and N stage as well as tumour height. Mesorectal fascia involvement, pre‐treatment carcinoembryonic antigen, age and comorbidity also influenced decision‐making to a lesser and more variable extent.

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Reviewers

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Issue Information

Cover of this issue. Cell clusters and cysts are rotated through distinct signaling mechanisms.see also Hirata et al. (pp. https://doi.org/10.1111/cas.138164045–4055 of this issue).

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Correction

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Lymph node resection induces the activation of tumor cells in the lungs

Abstract

Lymph node (LN) dissection is a crucial procedure for cancer staging, diagnosis and treatment and for predicting patient survival. Activation of lung metastatic lesions after LN dissection has been described for head and neck cancer and breast cancer. Preclinical studies have reported that dissection of a tumor‐bearing LN is involved in the activation and rapid growth of latent tumor metastases in distant organs, but it is also important to understand how normal (non‐tumor‐bearing) LN resection influences secondary cancer formation. Here, we describe how the resection of tumor‐bearing and non‐tumor‐bearing LNs affects distant metastases in MXH10/Mo‐lpr/lpr mice. Tumor cells were administered intravenously and/or intranodally into the right subiliac lymph node (SiLN) to create a mouse model of lung metastasis. Luciferase imaging revealed that tumor cells in the lung were activated after resection of the SiLN, irrespective of whether it contained tumor cells. No luciferase activity was detected in the lungs of mice that did not undergo LN resection (excluding the intravenous inoculation group). Our results indicate that resection of a LN can activate distant metastases regardless of whether the LN contains tumor cells. Hence, lung metastatic lesions are suppressed while metastatic LNs are present but activated after LN resection. If this phenomenon occurs in patients with cancer, it is likely that lung metastatic lesions may be activated by elective LN dissection in clinical N0 cases. The development of minimally invasive cancer therapy without surgery would help to minimize the risk of activation of distant metastatic lesions by LN resection.

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Detection of Circulating Tumor Cells with a Novel Microfluidic System in Malignant Pleural Mesothelioma

Abstract

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. The CellSearch, only approved system for clinical use, fails to capture EpCAM‐negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC‐chip) in which any antibody to capture CTCs is conjugated. The CTC‐chip was coated with an antibody against podoplanin that is abundantly expressed on MPM. CTC‐detection performances were evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC‐chip showed superior CTC‐detection performances over CellSearch in experimental models (sensitivity, 63.3 ‐ 64.5% versus 0 ‐ 1.1%; P<0.001) and in clinical samples (CTC‐positivity, 68.8% versus 6.3%; P<0.001). A receiver operating characteristics (ROC) analysis showed that the CTC‐test provided a significant diagnostic performance in discrimination of un‐resectable disease from resectable disease (area under ROC curve, 0.851; P=0.003). The higher CTC‐count (≥2cells/mL) was significantly associated with a poor prognosis (P=0.030). The novel CTC‐chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

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Glutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma

Summary

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. The proliferation of GSTP1 knockdown cells was significantly decreased (p<0.01), and the frequency of early apoptosis was increased (p<0.05). The invasion capacity of GSTP1 knockdown cells was slightly decreased in trans‐well assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug‐resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were performed. The viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (p<0.01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells　was markedly increased than that of control cells by cisplatin exposure (p<0.01). In immunohistochemistry assay of the resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (p=0.04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there is a significant association between the GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (p=0.02). In summary, GSTP1 was related to the malignant potential and may be a predictive marker of drug resistance in ESCC patients.

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Cyclohexanone curcumin analogs inhibit the progression of castration resistance prostate cancer in vitro and in vivo

Abstract

Many prostate cancer patients develop resistance to the treatment called castration‐resistant prostate cancer (CRPC), which is the major cause of recurrence and death. In this study, four cyclohexanone curcumin analogs were synthesized. Additionally, their anti‐cancer progression activity on CRPC cell lines, PC3 and PLS10 cells, was examined. We first determined their anti‐metastasis property and found that 2,6‐bis‐(4‐hydroxy‐3‐methoxy‐benzylidene)‐cyclohexanone (2A) and 2,6‐bis‐(3,4‐dihydroxy‐benzylidene)‐cyclohexanone (2F) exhibited higher anti‐invasion properties against CRPC cells than curcumin. Analog 2A inhibited both MMP‐2 and MMP‐9 secretions and activities, whereas analog 2F reduced only MMPs activities. These findings suggest that the compounds may inhibit CRPC cell metastasis via decreased extra cellular matrix degradation. Analog 2A, the most potent analog, was then subjected to the in vivo study. Similar to curcumin, analog 2A was detectable in the serum of mice at 30 and 60 min after intraperitoneal injections. Analog 2A and curcumin (30 mg/Kg BW) showed a similar ability to reduce tumor area in lungs of mice that were intravenously injected with PLS10 cells. Additionally, analog 2A showed superior growth inhibitory effect on PLS10 than that of curcumin both in vitro and in vivo. The compound inhibited PLS10 growth via induction of G1 phase arrest and apoptosis in vitro. Interestingly, analog 2A significantly decreased tumor growth with the down‐regulation of cell proliferation and angiogenesis in PLS10‐bearing mice. Taken together, we could summarize that analog 2A showed promising activities in inhibiting CRPC progression, both in vitro and in vivo.

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Biased emotional attention in patients with dental phobia

Abstract

Biased motivated attention towards phobia‐relevant pictures is a typical finding in specific phobia. In the visual system, the allocation of motivated attention is indexed by two event‐related potential components – the Early Posterior Negativity and the Late Positive Potential. Enhanced Early Posterior Negativity and Late Positive Potential amplitudes are reliably observed in specific phobia such as, for instance, snake, spider or blood‐injection‐injury phobia and to some extent also in dental phobia. However, regarding dental phobia results are sparse and its theoretical concept is not undisputed. To further elucidate the electrophysiological characteristics of dental phobia, we investigated visual emotional processing in dental phobia patients and controls. Subjects viewed neutral, phobia‐irrelevant and phobia‐relevant pictures while magnetoencephalographic and behavioral measures were recorded. All patients reported a history of traumatic experiences and depressive and anxiety symptoms, as well as dissociative and posttraumatic symptoms. In the magnetoencephalography, patients showed generally less evoked neural activation at parietal and temporal regions and a reduced differentiation between picture categories compared to controls. At the behavioral level, patients rated phobia‐relevant pictures as clearly more negative as did controls. In contrast to previous reports, our results suggest that dental phobia cannot be associated with the typical effects of biased motivated attention seen in other specific phobias. Instead, results indicate that dental phobia shares typical characteristics with mild forms of posttraumatic stress disorder.

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A Comprehensive Gene‐Environment Interaction Analysis in Ovarian Cancer using Genome‐wide Significant Common Variants

As a follow‐up to genome‐wide association analysis of common variants associated with ovarian carcinoma (cancer), this study considers seven well‐known ovarian cancer risk factors and their interactions with 28 genome‐wide significant common genetic variants. The interaction analyses were based on data from 9,971 ovarian cancer cases and 15,566 controls from 17 case‐control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs never) and rs13255292 (P‐value = 3.48 x 10^‐4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI=0.46‐0.60) compared to 0.71 (95%CI=0.66‐0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1‐5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene‐environment analysis in ovarian cancer.

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Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case‐control study, complemented with a Mendelian randomization (MR) approach in an independent case‐control sample. We used pre‐diagnostic biomarker data from 5,183 case‐control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls.

Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case‐control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study.

Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations.

We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [OR_log2B12] = 1.15, 95% confidence interval (95%CI) = 1.06‐1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [OR_SD]= 1.08, 95%CI= 1.00‐1.16).

Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

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Prognostic significance of microsatellite‐instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy

Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal‐junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse‐free survival and overall survival were calculated and correlated with MSI status. We identified the MSI‐H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI‐H patients, overall survival was significantly better for patients with MSI‐H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log‐rank test p=0.014). Among MSI‐H patients, an unexpected long‐term survival after relapse was observed. Our data indicate that the MSI‐H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI‐H gastric cancers, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI‐H tumors should be considered.

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Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: a prospective study

The constitutional t(11;22)(q23;q11) translocation is the only recurrent non‐Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long‐term prospective study of cancer and mortality risk in carriers.

We followed 65 male and 101 female carriers of t(11;22)(q23;q11) diagnosed in cytogenetic laboratories in Britain during 1976‐2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age‐, sex‐, country‐ and calendar‐period‐specific population rates.

Cancer incidence was borderline significantly raised for cancer overall (SIR=1.56, 95% CI: 0.98‐2.36, n=22), and significantly raised for invasive breast cancer (SIR=2.74, 95% CI: 1.18‐5.40, n=8) and in situ breast cancer (SIR=13.0, 95% CI: 3.55‐33.4, n=4). Breast cancer risks were particularly increased at ages <50 (SIR=4.37, 95% CI: 1.42‐10.2 for invasive, SIR=22.8, 95% CI: 2.76‐82.5 for in situ). Mortality was borderline significantly raised for breast cancer (SMR=4.82, 95% CI: 0.99‐14.1) but not significantly raised for other cancers or causes.

Individuals diagnosed with t(11;22)(q23;q11) appear to be at several‐fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers.

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Hot beverages and oesophageal cancer risk in western Kenya: findings from the ESCCAPE case‐control study

Oesophageal squamous cell carcinoma (ESCC) has markedly high incidence rates in Kenya and much of East Africa, with a dire prognosis and poorly understood aetiology. Consumption of hot beverages – a probable carcinogen to humans – is associated with increased ESCC risk in other settings and is habitually practiced in Kenya. We conducted a case‐control study in Eldoret, western Kenya between August 2013 and March 2018. Cases were patients with endoscopically confirmed oesophageal cancer whose histology did not rule out ESCC. Age and sex‐matched controls were hospital visitors and hospital out and in‐patients excluding those with digestive diseases. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for self‐reported drinking temperatures; consumption frequency; mouth burning frequency and hot porridge consumption using logistic regression models adjusted for potential confounders. Drinking temperature association with tumour sub‐location was also investigated. The study included 430 cases and 440 controls. Drinkers of "very hot" and "hot" beverages (>95% tea) had a 3.7 (95% CI: 2.1‐6.5) and 1.4‐fold (1.0‐2.0) ESCC risk, respectively compared to "warm" drinkers. This trend was consistent in males, females, never and ever alcohol/tobacco and was stronger over than under age 50 years. The tumour sub‐location distribution (upper/middle/lower oesophagus) did not differ by reported drinking temperature. This study is the first comprehensive investigation in this setting to‐date to observe a link between hot beverage consumption and ESCC in East Africa. These findings provide further evidence for the role of this potentially modifiable risk factor in ESCC aetiology.

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BRIVA‐LIFE – a multicentre retrospective study of the long‐term use of brivaracetam in clinical practice

Abstract

Objectives

Evaluate long‐term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy.

Materials and Methods

This was a multicentre retrospective study. Patients aged ≥16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety‐ and seizure‐related outcomes.

Results

575 patients were included in analyses; most had been treated with ≥4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were ≥50% responders and 17.5% were seizure‐free. Seizure‐freedom was achieved by 37.5% of patients aged ≥65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) were 39.8% and 14.3%, respectively, and discontinuation due to these were 8.9% and 3.7%, respectively. Somnolence, irritability and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10–15). Among those who switched because of PAEs (n=52), 9 (17%) reported PAEs on brivaracetam, and 3 (3.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity.

Conclusions

In a large population of patients with predominantly drug‐resistant epilepsy, brivaracetam was effective and well‐tolerated; no unexpected AEs occurred over 1 year and the incidence of PAEs was lower compared with levetiracetam.

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Leveraging patient‐reported outcomes data to inform oncology clinical decision making: Introducing the FACE‐Q head and neck cancer module

Background

Existing patient‐reported outcome measures (PROMs) used to assess patients with head and neck cancer have methodologic and content deficiencies. Herein, the development of a PROM that meets a range of clinical and research needs across head and neck oncology is described.

Methods

After development of the conceptual framework, which involved a literature review, semistructured patient interviews, and expert input, patients with head and neck cancer who were treated at Memorial Sloan Kettering Cancer Center were recruited by their surgeon. The FACE‐Q Head and Neck Cancer Module was completed by patients in the clinic or was sent by mail. Rasch measurement theory analysis was used for item selection for final scale development and to examine reliability and validity. Scale scores for surgical defect and adjuvant therapy were compared with the cohort average to assess clinical applicability.

Results

The sample consisted of 219 patients who completed the draft scales. Fourteen independently functioning scales were analyzed. Item fit was good for all 102 items, and all items had ordered thresholds. Scale reliability was acceptable (person separation index was >0.75 for all scales; Cronbach α values were >.87 for all scales; test‐retest ranged from 0.86 to 0.96). The scales performed well in a clinically predictable way, demonstrating functional and psychosocial differences across disease sites and with adjuvant therapy.

Conclusions

The scales forming the FACE‐Q Head and Neck Cancer Module were found to be clinically relevant and scientifically sound. This new PROM now is validated and ready for use in research and clinical care.

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Hispanic ethnicity as a moderator of the effects of aerobic and resistance exercise in survivors of breast cancer

Background

Metabolic syndrome (MSY) is associated with an increased risk of cardiovascular disease, type 2 diabetes, and recurrence in breast cancer survivors (BCS). MSY is 1.5 times more common in Hispanic women compared with non‐Hispanic women. Although exercise mitigates MSY in BCS, to the best of the authors' knowledge, few studies to date have focused on minorities. This secondary analysis examined ethnicity as a moderator of the effects of a 16‐week aerobic and resistance exercise intervention on MSY, sarcopenic obesity, and serum biomarkers in BCS.

Methods

A total of 100 eligible BCS were randomized to exercise (50 BCS) or usual care (50 BCS). The exercise intervention promoted moderate to vigorous aerobic and resistance exercise 3 times a week for 16 weeks. MSY z scores, sarcopenic obesity, and serum biomarkers were measured at baseline, after the intervention, and at the 28‐week follow‐up (exercise group only). Linear mixed models adjusted for baseline values of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity.

Results

The study sample was 57% Hispanic BCS (HBCS) and 43% non‐Hispanic BCS (NHBCS). HBCS were younger, of greater adiposity, and had been diagnosed with more advanced cancers compared with NHBCS (P<.001). Ethnicity was found to moderate the mean differences in exercise training on triglycerides (‐36.4 mg/dL; 95% confidence interval [95% CI],‐64.1 to ‐18.8 mg/dL), glucose (‐8.6 mg/dL; 95% CI, ‐19.1 to ‐3.0 mg/dL), and C‐reactive protein (‐3.3 mg/L; 95% CI, ‐7.3 to ‐0.9 mg/L).

Conclusions

HBCS appear to have poorer metabolic profiles and therefore may derive relatively larger metabolic changes from exercise compared with NHBCS. Clinical exercise interventions may attenuate existing health disparities across diverse groups of BCS.

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