Purpose of review The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives. Recent findings Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one's genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and μ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug–gene pairs studied continue to expand. Summary Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings. Correspondence to Senthilkumar Sadhasivam, MD, MPH, Gopal Krishna Professor and Chief of Anesthesia, Department of Anesthesia, Riley Hospital for Children at Indiana University Health, RH 2835, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA. Tel: +1 317 948 3845; fax: +1 317 944 0282; e-mail: ssadhasivam@iuhealth.org Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2py37CJ
Πέμπτη 20 Σεπτεμβρίου 2018
Oncogene Delta/Notch-Like EGF-Related Receptor Promotes Cell Proliferation, Invasion, and Migration in Hepatocellular Carcinoma and Predicts a Poor Prognosis
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2xESyRS
NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFR
NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFR
NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFR, Published online: 20 September 2018; doi:10.1038/s41419-018-0953-7
NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFRhttps://ift.tt/2Nqzfq2
Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinoma
Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinoma
Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinoma, Published online: 20 September 2018; doi:10.1038/s41419-018-0965-3
Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinomahttps://ift.tt/2DhCOtX
Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling
Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling
Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling, Published online: 20 September 2018; doi:10.1038/s41419-018-0999-6
Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signalinghttps://ift.tt/2Nqy35W
CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance
CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance
CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance, Published online: 20 September 2018; doi:10.1038/s41419-018-0974-2
CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistancehttps://ift.tt/2DjxM00
Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cells
Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cells
Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cells, Published online: 20 September 2018; doi:10.1038/s41419-018-0958-2
Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cellshttps://ift.tt/2Nqy0XO
p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis
p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis
p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis, Published online: 20 September 2018; doi:10.1038/s41419-018-0984-0
p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesishttps://ift.tt/2DhCHP3
MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting β-catenin and CDK2 and activating p21
MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting β-catenin and CDK2 and activating p21
MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting β-catenin and CDK2 and activating p21, Published online: 20 September 2018; doi:10.1038/s41419-018-0986-y
MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting β-catenin and CDK2 and activating p21https://ift.tt/2NwDRex
RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signaling
RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signaling
RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signaling, Published online: 20 September 2018; doi:10.1038/s41419-018-0972-4
RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signalinghttps://ift.tt/2DhCGdX
Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode system
Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. An...
https://ift.tt/2Nr2by5
Epileptic spasms in PPP1CB-associated Noonan-like syndrome: a case report with clinical and therapeutic implications
Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2) is an extremely rare disease caused by a heterozygous mutation in the PPP1CB gene on chromosome 2p23. The syndrome causes not only numerous dysmor...
https://ift.tt/2ONnS84
Factors associated with favourable outcome in large hemispheric infarctions
Large hemispheric infarction (LHI) is a devastating condition with high mortality and poor functional outcome in most conservatively treated patients. The purpose of this study was to explore factors associate...
https://ift.tt/2O0tI96
The psychometric properties of the Childhood Health Assessment Questionnaire (CHAQ) in children with cerebral palsy
The evaluation of children with cerebral palsy (CP) focuses on activity level measurement to examine the effect of health-care interventions on their physical functioning in the home, school, and community set...
https://ift.tt/2NZTF8H
Mutation m.15923A>G in the MT-TT gene causes mild myopathy – case report of an adult-onset phenotype
Only five patients have previously been reported to harbor mutations in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G mutation has been found in three severely affected children. One of t...
https://ift.tt/2OGBOAT
Urological dysfunctions in patients with Parkinson’s disease: clues from clinical and non-invasive urological assessment
Autonomic nervous system dysfunction, common in patients with Parkinson's disease (PD), causes significant morbidity and it is correlated with poor quality of life. To assess frequency of urinary symptoms in p...
https://ift.tt/2O54vdW
Genomic Analysis To Identify Signatures of Artificial Selection and Loci Associated with Important Economic Traits in Duroc Pigs
Identifying genetic basis of domestication and improvement in livestock contributes to our understanding of the role of artificial selection in genome shaping. Here we used whole-genome sequencing and the genotyping by sequencing approach to detect artificial selection signatures and identify the associated SNPs of two economic traits in Duroc pigs. A total of 38 candidate selection regions were detected by combining the fixation index and the Composite Likelihood Ratio methods. Further genome-wide association study revealed 7 associated SNPs that were related with intramuscular fat content and feed conversion ratio traits, respectively. Enrichment analysis suggested that the artificial selection regions harboured genes, such as MSTN, SOD2, MC5R and CD83, which are responsible for economic traits including lean muscle mass, fertility and immunization. Overall, this study found a series of candidate genes promising to associate with the breeding improvement of Duroc pigs and the polygenic basis of adaptive evolution, which can provide important references and fundamental information for future breeding programs.
https://ift.tt/2Nw1rrJ
Black Individuals at Highest Risk of Legal Intervention Injury
THURSDAY, Sept. 20, 2018 -- Black males were at the highest risk of legal intervention injury per capita from 2005 to 2015, according to a study published online Sept. 14 in JAMA Network Open. Alyssa C. Mooney, M.P.H., from the University of...
https://ift.tt/2DtGZmP
Educational Disabilities More Likely With Neonatal Abstinence
THURSDAY, Sept. 20, 2018 -- Children with a history of neonatal abstinence syndrome (NAS) are more likely to be referred for a disability evaluation and meet criteria for a disability, according to a study published in the September issue of...
https://ift.tt/2NvRhr5
Cannabinoid Trials Needed for Peds Neurologic Disorders
THURSDAY, Sept. 20, 2018 -- There is an urgent need for clinical trials to investigate the use of cannabinoids in pediatric patients with neurological disorders, according to a commentary published in the Aug. 27 issue of CMAJ, the journal of the...
https://ift.tt/2DkbFH3
Study Provides Estimates of U.S. Prevalence of Type 1, 2 Diabetes
THURSDAY, Sept. 20, 2018 -- The prevalence of type 1 and type 2 diabetes is 0.5 and 8.5 percent, respectively, among U.S. adults, according to a study published online Sept. 4 in The BMJ. Guifeng Xu, M.D., from the University of Iowa in Iowa City,...
https://ift.tt/2NscyBH
Research Links Doctor Burnout to Patient Safety Incidents
THURSDAY, Sept. 20, 2018 -- Physician burnout is associated with increased risk of patient safety incidents, poorer quality of care due to low professionalism, and reduced patient satisfaction, according to a review published online Sept. 4 in JAMA...
https://ift.tt/2DegBgm
Induction of innate immune memory: the role of cellular metabolism
Jorge Domínguez-Andrés | Leo AB Joosten | Mihai G Netea
https://ift.tt/2xEoc1S
Migrant and refugee populations: a public health and policy perspective on a continuing global crisis
The 2015–2017 global migratory crisis saw unprecedented numbers of people on the move and tremendous diversity in terms of age, gender and medical requirements. This article focuses on key emerging public heal...
https://ift.tt/2ps1xlH
Monitoring of Blood Pressure is not Enough to Avoid Neonatal Postoperative Encephalopathy
AJP Rep 2018; 08: e192-e194
DOI: 10.1055/s-0038-1668565
Background Neonatal encephalopathy with seizures after general anesthesia not occurring in infants undergoing cardiac or major neurosurgery is very uncommon. An ischemic origin due to cerebral hypoperfusion from perioperative hypotension has been suggested, but there is a lack of a consensus definition for intraoperatory hypotension in neonates. Case Report We report the first case of neonatal encephalopathy with seizures in a neonate with anorectal malformation. He underwent a colostomy with caudal anesthesia combined with light general anesthesia. Intraoperative systolic blood pressure and mean blood pressure values were considered normal. Thirty-two hours after the intervention, the patient presented electroclinical seizures. Diffusion-weighted imaging showed bilateral involvement with reduced diffusivity in the watershed areas of the middle cerebral artery and posterior cerebral artery. Conclusion Perioperative monitoring of blood pressure is not enough in neonatal surgery. Cerebral magnetic resonance imaging should be considered in infants with noncardiac congenital anomalies after neonatal surgery and long-term follow-up is required.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
https://ift.tt/2OGdejB
Renal failure in critically ill patients, beware of applying (central venous) pressure on the kidney
The central venous pressure (CVP) is traditionally used as a surrogate of intravascular volume. CVP measurements therefore are often applied at the bedside to guide fluid administration in postoperative and cr...
https://ift.tt/2Dh7jAj
Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis
To determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit (ICU) delirium.
https://ift.tt/2Np2hXb
Comparing postoperative complication of LigaSure Small Jaw instrument with clamp and tie method in thyroidectomy patients: a randomized controlled trial [IRCT2014010516077N1]
Abstract
Background
LigaSure® Small Jaw (LSJ) has been recently introduced as an energy-based vessel sealing device, which has provided better intraoperative and postoperative outcomes in thyroidectomies, compared to conventional technique. In the current study, we aimed to examine the efficiency of hand-sewn and LSJ thyroidectomy, based on operation time and perioperative complications.
Methods
All patients with the diagnosis of multinodular goiter, thyroid cancers, retrosternal goiter and other indications for thyroid surgeries, enrolled. Of 550 patients, 261 patients randomly assigned to the conventional group (A) and 274 patients to LigaSure Small Jaw group (B). Study groups compared concerning operative time, recurrent laryngeal nerve (RLN) injury, hypocalcemia, and postoperative complications.
Results
There was no significant difference regarding demographic data between groups A and B. During total thyroidectomy, intraoperative blood loss was 64.42 ± 20.72 ml and 49.64 ± 17.92 ml in groups A and B, respectively (P 0.043). Operative time was significantly lower in LSJ group compared to the conventional group in total and subtotal thyroidectomy (P 0.002; P 0.001). Three patients who underwent conventional total thyroidectomy had RLN palsy. However, there was no significant difference between techniques regarding RLN injury (P 0.134).
Postoperative total and ionized serum calcium levels decreased compared to preoperative levels in both conventional and LSJ technique; however, changes in total and ionized serum calcium were more severe in patients with conventional thyroidectomy (total calcium, P < 0.0001) (ionized calcium, P 0.005).
Conclusion
The LigaSure Small Jaw device decreases operative time and intraoperative bleeding compared to conventional technique. Besides, changes in total and ionized calcium levels in patients with LSJ thyroidectomy are subtle compared to HS technique.
Trial registration
Registered in Iranian Registry of Clinical Trials (www.irct.com), trial registration: IRCT2014010516077N1, Registered: 23 May 2014).
https://ift.tt/2Nwds0p
Adjuvant Chemotherapy in Rectal Cancer Patients Treated with Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study
In this multi-institutional and retrospective analysis, we evaluated 1,442 patients with rectal cancer who received preoperative chemoradiotherapy (CRT) and curative surgery. After propensity-score matching, 1,225 patients who received adjuvant chemotherapy were matched with the 217 observed patients after curative surgery in a 1:4 ratio. After matching analysis, 5-FU based adjuvant chemotherapy after preoperative CRT followed by total mesorectal excision was not significantly associated with improved relapse-free survival for patients with locally advanced rectal cancer.
https://ift.tt/2xpAyLW
Late Sequelae of Childhood and Adolescent Nasopharyngeal Carcinoma Survivors after Radiotherapy
This study examined the long-term sequelae of children and adolescent nasopharyngeal carcinoma (NPC) survivors after radiotherapy. Comparing with convention radiotherapy treatment (CRT), intensity-modulated radiotherapy treatment (IMRT) can potentially ameliorate xerostomia, dysphagia and otitis media in survivors. Besides, patients younger than 10 years old had a higher cumulative incidence (CI) of blurred vision. Moreover, a dose of more than 72 Gray (Gy) to primary tumor increased the CI of hearing loss, lalopathy and cranial nerve injury.
https://ift.tt/2PTj8hz
Predictors of early recurrence prior to planned post-operative radiation therapy for oral cavity squamous cell carcinoma and outcomes following salvage intensified radiation therapy
Identification of recurrence before planned PORT in OSCC is critical to allow treatment intensification. Retrospective review was performed for 601 OSCC patients treated with PORT following curative-intent surgery. We have identified rates and risk factors of early recurrence, and predictors of outcomes following salvage therapy with higher dose PORT+/-concurrent chemotherapy. Understanding the characteristics and outcomes of this very high-risk group may allow alternate treatment strategies to be explored in the future.
https://ift.tt/2xu6nmG
EMS Agenda 2050 Quick Take: Focusing on people – providers, patients, families – is the future of EMS
The EMS Agenda 2050 outlines six guiding principles for the future of emergency medical services
https://ift.tt/2xCHZih
Association between diastolic cardiac dysfunction and nonalcoholic fatty liver disease: A systematic review and meta-analysis
Recent studies have suggested an association between nonalcoholic fatty liver disease (NAFLD) and diastolic cardiac dysfunction, although the results were inconsistent. This study was conducted to investigate this possible association.
https://ift.tt/2MQlmw7
Statin use is associated to a reduced risk of pancreatic cancer: A meta-analysis
Previous studies investigating the association between statin use and pancreatic cancer (PDAC) risk for a possible chemopreventive effect gathered heterogeneous results.
https://ift.tt/2MSCt0i
EMS Agenda 2050 Quick Take: Focusing on people – providers, patients, families – is the future of EMS
The EMS Agenda 2050 outlines six guiding principles for the future of emergency medical services
https://ift.tt/2xCHZih
Reply
We thank Dr Kendall for his interest in our observational cohort study of 99 patients admitted to the pediatric cardiac ICU (CICU) of a tertiary care center, including 88 who underwent cardiac surgery and 11 who were admitted for medical reasons. We found an incidence of delirium of 57% (95% CI, 46%-67%) in the overall cohort, 59% (95% CI, 49%-69%; n = 52) in the surgical patients, and 36% (95% CI, 15%-65%; n = 4) in the medical patients. Delirious pediatric patients undergoing cardiac surgery were more likely to be male (P = .018), to be younger (P < .001), and to have cyanotic heart disease (P = .048).
https://ift.tt/2QQbl5B
Covariation of Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Management and In-Neonatal Intensive Care Unit Outcomes Following Preterm Birth
To test the hypothesis that neonatal intensive care unit (NICU)-specific changes in patent ductus arteriosus (PDA) management are associated with changes in local outcomes in preterm infants.
https://ift.tt/2xDZkr2
Reply
We appreciate the thoughtful letter by Drs Thienemann and Frankovich in response to our commentary in which we evaluated pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) research and provided diagnostic and therapeutic recommendations. Their reply was framed in terms of decision-making under conditions of uncertainty, and they cogently described challenges faced by clinicians, particularly in the neurosciences, when we encounter suffering children and families and unclear underlying biology.
https://ift.tt/2QNZJ2F
Adiposity in Adolescents: The Interplay of Sleep Duration and Sleep Variability
To assess whether adiposity measures differed according to joint categories of sleep duration and sleep variability in a sample of Mexican adolescents.
https://ift.tt/2QQbfuL
Lifestyle Clusters in School-Aged Youth and Longitudinal Associations with Fatness: The UP&DOWN Study
To identify lifestyle clusters in children and adolescents, to analyze associations between lifestyle clusters and body fat percentage (BFP) at baseline and 2 years later, and to examine if BFP at baseline is associated with BFP 2 years later.
https://ift.tt/2xATpD9
Optimal Mean Arterial Blood Pressure in Extremely Preterm Infants within the First 24 Hours of Life
To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest (MABPOPT) during the early transitional circulation in extremely preterm infants and to investigate the association between deviations above and below MABPOPT with intraventricular hemorrhage (IVH) and mortality.
https://ift.tt/2QQbhTp
Vitamin D Status at the Time of Hospitalization for Bronchiolitis and Its Association with Disease Severity
To investigate the association between circulating 25-hydroxyvitamin D [25(OH)D] status at admission and disease severity among infants hospitalized for bronchiolitis and to determine whether the association differs by the form of 25(OH)D—total, bioavailable or free 25(OH)D.
https://ift.tt/2xA1JD3
HIV–Associated Diffuse Intracranial Aneurysmal Arteriopathy
A 12-year-old boy presented with sudden weakness of his right upper and lower limbs, with facial deviation. He was HIV positive and was receiving antiretroviral therapy for 1 year. Cerebral computed tomography angiography of the brain revealed aneurysmal dilatation and dolichoectasia involving the intracranial vessels (Figure).
https://ift.tt/2xDPWUl
If You Build It, Will They Come? Getting Medical Professionals to Use the Bridge of Evidence for Improved Recognition of Physical Child Abuse
The old adage "you can prevent what you can predict" may very well be true, but only if the right people have access to the knowledge and if they apply it in a timely manner, correctly, consistently, and systematically. Unfortunately, the medical profession is known for its resistance to change and long lag times to adapt new evidence into practice.1,2 As reported by the Agency for Health Research and Quality, "It may take as long as one or two decades for original research to be put into routine clinical practice.
https://ift.tt/2xDEt75
A Metadata Extraction Approach for Clinical Case Reports to Enable Advanced Understanding of Biomedical Concepts
We present a protocol and associated metadata template for the extraction of text describing biomedical concepts in clinical case reports. The structured text values produced through this protocol can support deep analysis of thousands of clinical narratives.
https://ift.tt/2poZEGr
Excess vascular endothelial growth factor-A disrupts pericyte recruitment during blood vessel formation
Abstract
Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations. Pericytes had little to no expression of VEGF receptors, suggesting VEGF-A signaling defects affect endothelial cells directly but pericytes indirectly. Live imaging of ex vivo angiogenesis in mouse embryonic skin revealed limited pericyte migration during exposure to exogenous VEGF-A. During VEGF-A gain-of-function conditions, pericytes and endothelial cells displayed abnormal transcriptional changes within the platelet-derived growth factor-B (PDGF-B) and Notch pathways. To further test potential crosstalk between these pathways in pericytes, we stimulated embryonic pericytes with Notch ligands Delta-like 4 (Dll4) and Jagged-1 (Jag1) and found induction of Notch pathway activity but no changes in PDGF Receptor-β (Pdgfrβ) expression. In contrast, PDGFRβ protein levels decreased with mis-regulated VEGF-A activity, observed in the effects on full-length PDGFRβ and a truncated PDGFRβ isoform generated by proteolytic cleavage or potentially by mRNA splicing. Overall, these observations support a model in which, during the initial stages of vascular development, pericyte distribution and coverage are indirectly affected by endothelial cell VEGF-A signaling and the downstream regulation of PDGF-B-PDGFRβ dynamics, without substantial involvement of pericyte Notch signaling during these early stages.
https://ift.tt/2O0Z3bC
Reply
We appreciate the interest of Li et al in our work and are grateful for the opportunity to address the points they raised.
https://ift.tt/2NutW8W
Issue Highlights
Studies have shown a positive association between systemic markers of inflammation and the risk of future cardiovascular disease. It is believed that this risk is mediated by prothrombotic changes in the vasculature as a response to inflammation. Systemic inflammatory diseases such as inflammatory bowel disease (IBD) may increase the risk for coronary artery disease by this mechanism, although prior epidemiologic studies show mixed results. In this issue of Clinical Gastroenterology and Hepatology, Aniwan and colleagues1 evaluated the risk of acute myocardial infarction and heart failure in patients with ulcerative colitis (UC) and Crohn's disease.
https://ift.tt/2Ns2rgo
Barrett’s Esophagus
Barrett's esophagus occurs when the cells lining the esophagus (the tube that links your mouth and stomach) change into abnormal cells, increasing the risk of long-term problems. It does not cause any symptoms that you can feel, but it puts you at greater risk for a type of cancer that forms in the esophagus. The true cause is unknown, but there are a few things that could increase your chances of getting it, such as:
https://ift.tt/2DsUXW3
The Association Between Consumption of Sweetened Beverages and the Risk of Inflammatory Bowel Disease
We read with interest the article by Khalili et al1 investigating the association between consumption of sweetened beverages and later risk of Crohn's disease or ulcerative colitis. The author observed no evidence for associations between consumption of sweetened beverages and later risk of Crohn's disease or ulcerative colitis from 2 large prospective cohort studies from Sweden. Because their findings are different from previous studies, this issue deserves further discussion.
https://ift.tt/2Dhixou
Outcomes of Endoscopic Balloon Dilation vs Surgical Resection for Primary Ileocolic Strictures in Patients With Crohn’s Disease
We read with great interest the article by Lan et al.1 This retrospective study identified that there is a high frequency of salvage surgery although endoscopic balloon dilation is successful initially with minimal adverse events, and initial ileocolic resection is associated with a higher morbidity but a longer surgery-free interval. Herein, we would like to raise the following comments.
https://ift.tt/2NuqCe4
Opioid Toxicity in Inflammatory Bowel Disease Patients Likely Includes Direct Enterocyte Effects That Exacerbate Disease
We read the article by Burr et al1 with great interest. Opioid use in patients with inflammatory bowel disease is unfortunately all too common, and it is important that the risks of opioid therapy in this population be well understood. The authors mention several possible mechanisms by which opioids may be increasing mortality, including canonical opioid toxicities (such as respiratory depression), and that opioid use may be associated with more severe disease and thus worse outcomes.
https://ift.tt/2DfMa9t
That Cursed Dyspepsia
Koduru et al1 are to be congratulated for their article regarding dyspepsia. The authors take a gargantuan beast and describe its shape, characteristics, habits, how it has grown and changed over many years, along with the best ways to understand it and deal with it.
https://ift.tt/2DqlGm6
Allopurinol Dose Escalation for Gout Doesn't Improve Mortality
THURSDAY, Sept. 20, 2018 -- Allopurinol dose escalation is not associated with reductions in mortality risk among patients with gout, according to a study published in the August issue of Arthritis & Rheumatology. Brian W. Coburn, Ph.D., from...
https://ift.tt/2DeRoCI
Combo Physical, Mental Activity Prevents Cognitive Decline
THURSDAY, Sept. 20, 2018 -- Behavioral activation that increases mental, physical, and social activity may prevent cognitive and functional decline in older black patients, according to a study published online Sept. 10 in JAMA Neurology. Barry W....
https://ift.tt/2xqytzg
Statins Improve Long-Term Survival After AAA Repair
THURSDAY, Sept. 20, 2018 -- Preoperative statin therapy is associated with higher long-term survival following abdominal aortic aneurysm (AAA) repair, according to a study published in the August issue of the Journal of Vascular Surgery. Thomas F.X....
https://ift.tt/2DfXPVP
Few Yogurt Products Qualify As Low-Sugar
THURSDAY, Sept. 20, 2018 -- There is considerable variability in the sugar content of yogurts, with very few yogurts qualifying as low-sugar, according to a study published in the August issue of BMJ Open. J. Bernadette Moore, Ph.D., from the...
https://ift.tt/2xqysvc
Crowdfunding for Cancer Tx Could Exploit Vulnerable Patients
THURSDAY, Sept. 20, 2018 -- There are fears that huge sums are being raised on crowdfunding sites for alternative cancer treatments that are not backed by evidence, according to a feature article published online Sept. 12 in The BMJ. Melanie Newman,...
https://ift.tt/2DeRlXy
Hospitals Charge 479 Percent of Cost of Drugs on Average
THURSDAY, Sept. 20, 2018 -- On average, hospitals mark up drugs by 479 percent of their cost, according to a report from The Moran Company, commissioned by the Pharmaceutical Research and Manufacturers of America (PhRMA). Researchers from The Moran...
https://ift.tt/2xs0VRr
>60 Percent of Adults Report Adverse Childhood Experiences
THURSDAY, Sept. 20, 2018 -- More than 60 percent of adults report having had at least one adverse childhood experience (ACE), and almost 25 percent report three or more, according to a study published online Sept. 17 in JAMA Pediatrics. Melissa T....
https://ift.tt/2DfEi7V
Cardiac Monitoring Needed for High-Risk Breast Cancer Patients
THURSDAY, Sept. 20, 2018 -- Risk of cardiotoxicity is higher for patients receiving trastuzumab and/or anthracyclines for the treatment of breast cancer, according to a study published in the Aug. 1 issue of JACC: Cardiovascular Imaging. Mariana L....
https://ift.tt/2xqyovs
Residents Should Take Advantage of Paid Time Off
THURSDAY, Sept. 20, 2018 -- Although there are many demands on residents, taking advantage of paid vacation time is one of the perks and should be maximized, according to an article published in the American Medical Association's AMA...
https://ift.tt/2Djftbz
Nivolumab and Ipilimumab Effective against Melanoma That Has Spread to the Brain
Results from a clinical trial show that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) halted the growth of or shrank metastatic brain tumors in more than half of participants with melanoma that had spread to the brain.
https://ift.tt/2O0siLM
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Regulation of the chromatin environment is an essential process required for proper gene expression. Here, we describe a method for controlling gene expression through the recruitment of chromatin-modifying machinery in a gene-specific and reversible manner.
https://ift.tt/2PNIwoO
What an Entangled Web We Weave: An Information-centric Approach to Time-evolving Socio-technical Systems
Abstract
A new layer of complexity, constituted of networks of information token recurrence, has been identified in socio-technical systems such as the Wikipedia online community and the Zooniverse citizen science platform. The identification of this complexity reveals that our current understanding of the actual structure of those systems, and consequently the structure of the entire World Wide Web, is incomplete, which raises novel questions for data science research but also from the perspective of social epistemology. Here we establish the principled foundations and practical advantages of analyzing information diffusion within and across Web systems with Transcendental Information Cascades, and outline resulting directions for future study in the area of socio-technical systems. We also suggest that Transcendental Information Cascades may be applicable to any kind of time-evolving system that can be observed using digital technologies, and that the structures found in such systems comprise properties common to all naturally occurring complex systems.
https://ift.tt/2QJHUls
Research Analysis: Key takeaways from PART and Airways-2 Trials
Comparing endotracheal, laryngeal tube and supraglottic airway device intubation during out of hospital cardiac arrest
https://ift.tt/2MPc2ZE
What you missed at the 2018 Pinnacle Leadership Forum
Pinnacle program co-chair, Jay Fitch, recounts the highlights from this year's leadership forum
https://ift.tt/2pqTZQ8
Being PrEPared — Preexposure Prophylaxis and HIV Disparities
If current trends persist, one in six U.S. men who have sex with men will be infected with human immunodeficiency virus (HIV) in their lifetime, according to the Centers for Disease Control and Prevention (CDC). This prediction highlights the long road ahead if we are to end the spread of HIV in…
https://ift.tt/2DsDUU3
Payment and Delivery-System Reform — The Next Phase
After nearly a decade of experimentation with value-based payment (VBP), U.S. health care payers, providers, and purchasers are confronting uneven adoption of new care guidelines, modest early results, and still-unacceptable gaps in spending and quality. In determining what comes next, we believe…
https://ift.tt/2NsxIQt
[18F]FDG-Labeled CGPRPPC Peptide Serving as a Small Thrombotic Lesions Probe, Including a Comparison with [99mTc]-Labeled Form
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2xKVP2b
A Qualitative Study of Psychological Outcomes in Avalanche First Responders
High Altitude Medicine &Biology, Ahead of Print.
https://ift.tt/2DsEFMT
Being PrEPared — Preexposure Prophylaxis and HIV Disparities
If current trends persist, one in six U.S. men who have sex with men will be infected with human immunodeficiency virus (HIV) in their lifetime, according to the Centers for Disease Control and Prevention (CDC). This prediction highlights the long road ahead if we are to end the spread of HIV in…
https://ift.tt/2DsDUU3
Payment and Delivery-System Reform — The Next Phase
After nearly a decade of experimentation with value-based payment (VBP), U.S. health care payers, providers, and purchasers are confronting uneven adoption of new care guidelines, modest early results, and still-unacceptable gaps in spending and quality. In determining what comes next, we believe…
https://ift.tt/2NsxIQt
Dynamic Adhesion Assay for the Functional Analysis of Anti-adhesion Therapies in Inflammatory Bowel Disease
Dynamic adhesion of immune cells to the vessel wall is a prerequisite for gut homing. Here, we present a protocol for a functional in vitro assay for the impact analysis of anti-integrin antibodies, chemokines or other factors on the dynamic cell adhesion of human cells using addressin-coated capillaries.
https://ift.tt/2O0gTvs
Anogenital Distance and Perineal Measurements of the Pelvic Organ Prolapse (POP) Quantification System
This manuscript describes the procedures to perform anogenital distance (AGD) and perineal measurements standardized by the Pelvic Organ Prolapse Quantification System (POP-Q): perineal body (PB) and genital hiatus (GH). These measurements are compared in women with and without pelvic organ prolapse.
https://ift.tt/2OHPefR
pH and a mixed carbon-substrate spectrum influence FocA- and FocB-dependent, formate-driven H2 production in Escherichia coli
Abstract
Escherichia coli encodes two formate channels, FocA and FocB, which either export formate or import it for further disproportionation by the formate hydrogenlyase (FHL) complex to H2 and CO2. We show that FocA/B appear to change their substrate-translocation direction depending on pH and electron donor. When cells were grown on glucose and glycerol at pH 7.5 formate accumulated in focB or focA-focB mutants when glucose or formate was used as electron donor because H2 production increased ∼2 and ∼1.5 fold, respectively. Moreover, addition of external formate to the growth medium increased H2 production in a focA-focB mutant. This indicates that in the wild type, formate is preferentially exported at pH 7.5 and that another FocA/B-independent uptake system exists. At pH 6.5 and 5.5 the formate channel mutants showed reduced H2 production, suggesting that formate is usually imported by them to produce H2 at acidic pH. Addition of formate to the growth medium increased H2 production at these pHs. Notably, glycerol failed to act as an effective electron donor for formate production. Taken together, our results suggest that regulation of formate translocation direction by FocA/FocB channels is important for maintaining internal pH and proton motive force by modulating H2 production.https://ift.tt/2xsxuia
The Smallest Intestine (TSI) – a low volume in vitro model of the small intestine with increased throughput
Abstract
There is a growing interest in understanding the fate and behaviour of probiotic microorganisms and bioactive compounds during passage of the human gastrointestinal tract (GIT). Here we report the development of a small volume in vitro model called The smallest Intestine (TSI) with increased throughput focusing on simulating passage through the stomach and small intestine (SI). The basic TSI module consists of 5 reactors, with a working volume of 12 ml each. During the simulated passage through the SI, bile is absorbed and pH is adjusted to physiologically relevant values for duodenum, jejunum and ileum. A consortium of seven representative bacterial members of the ileum microbiota is included in the ileal stage of the model. The behaviour of 3 putative probiotic Lactobacillus strains during in vitro simulated upper GIT passage was tested in the model and results were compared to previous studies describing probiotic survival. It was found, that probiotic persistence is strongly related to whether food was ingested, but also to presence of the ileal microbiota, which significantly impacted probiotic survival. In conclusion TSI allows testing a substantial number of samples, at low cost and short time, and is thus suitable as an in vitro screening platform.https://ift.tt/2PQRcdY
Highly Cited Papers in Microbiology: Identification and Conceptual Analysis
Abstract
Microbiology is an area with a high research production, classified in different branches. Thus, it is difficult to identify research trends without many backgrounds. The present paper aims to apply bibliometric methods to identify the highly cited papers that contribute to the Microbiology development. Furthermore, a science mapping analysis allows discovering the main thematic areas covered by those detected papers. From the 572,153 papers (articles and reviews) indexed in the Web of Science Microbiology category (1900–2017), a total of 645 highly cited papers were detected. Concerning the main scientific producers in Microbiology, Applied and Environmental Microbiology as a journal, R. Knight from the University of Colorado (USA) as an author, and the USA as a country are the most productive actors. Nevertheless, taking into account the gross domestic product (GDP) per capita, China and Spain are remarkable countries. Furthermore, according to the relative priority index (RPI), Denmark, Belgium, Spain, and The Netherlands are the countries that make a higher scientific effort in this field. About the co-word analysis, several important themes were detected, such as Next Generation Sequencing, Gene, Escherichia Coli or Gene Expression. Concerning these results, this work supposes a framework on which to base future research.https://ift.tt/2xtAmv0
Sterilization impacts on marine sediment – Are we able to inactivate microorganisms in environmental samples?
Abstract
To distinguish between biotic and abiotic processes in laboratory experiments with environmental samples, an effective sterilization method is required that prevents biological activity but does not change physico-geochemical properties of samples. We compared standard sterilization methods with respect to their impact on microbial abundance and activity. We exposed marine sediment to i) autoclaving, ii) gamma-radiation or iii) sodium azide (NaN3) and determined how nucleic acids, microbial productivity, colony forming units (CFUs), and community composition of microorganisms, fungi, unicellular protists, and protozoa were affected. In autoclaved and gamma-sterilized sediments, only few colonies formed within 16 days. After addition of NaN3 to the sediment, numerous CFUs (>50) but lower 3H-leucine incorporation rates, i.e. lower protein biosynthesis rates, were found compared to the other two sterilization techniques. Extractable RNA was detected immediately after all sterilization treatments (0.2–17.9 ng/g dry sediment) but decreased substantially by 84-98% after 16 days of incubation. The total organic carbon content increased from 18 mg L−1 to 220 mg L−1 (autoclaving) and 150 mg L−1 (gamma radiation) after sterilization. We compare advantages and disadvantages for each tested sterilization method and provide a helpful decision-making resource for choosing the appropriate sterilization technique for environmental studies, particularly for marine sediments.https://ift.tt/2DixmXX
A salamander's top down effect on fungal communities in a detritivore ecosystem
Abstract
The soil decomposer community is a primary driver of carbon cycling in forest ecosystems. Understanding the processes that structure this community is critical to our understanding of the global carbon cycle. In North American forests, soil fungal communities are regulated by grazing soil invertebrates, which are in turn controlled by the predatory red-backed salamander (Plethodon cinereus). The presence of these soil invertebrate taxa are known to exert direct top-down control via selective grazing on saprotrophic fungi, with direct consequences for biogeochemical cycling in soil. We investigated whether the removal of P. cinereus would relieve top-down control on decomposer fungal communities in a tri-trophic mesocosm study. Fungal communities were characterized using metabarcoding and high-throughput DNA sequencing. The β-diversity of fungal communities differed between salamander presence and absence treatments with a strong effect on saprotrophic fungal communities. We concluded that P. cinereus, a mesopredator in the detritivore food chain, exerts a prominent control on the composition and functional diversity of fungal communities in soil through a multi-trophic top-down process. Given their capacity to govern the compositions of soil invertebrates, the activity of these amphibians may be important for regulating ecosystem function and nutrient cycling in temperate forest systems.https://ift.tt/2NsxjNU
Molecular identification of some wild Nigerian mushrooms using internal transcribed spacer: polymerase chain reaction
Identification of fungal species based on morphological characteristics is tedious, complex, prone to errors, and thus cannot be completely relied upon. In this study, internal transcribed spacers (ITS 1 and 4...
https://ift.tt/2prioFc
Early histological, microbiological, radiological, and clinical response to cemented and screw‐retained all‐ceramic single crowns
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2MPOP9F
Analysis of osseointegration of implants with hydrophilic surfaces in grafted areas: A Preclinical study
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2pmyIXL
Use of PEG-asparaginase in a case of Hepatosplenic γδ T-cell lymphoma with long-term remission after stem cell transplantation
Kai Sun, Cesar Gentille Sanchez, Sai Ravi Pingali and Swaminathan Iyer
https://ift.tt/2MNR6lK
The role of obesity in the fatal outcome of Schaaf–Yang syndrome: Early onset morbid obesity in a patient with a MAGEL2 mutation
American Journal of Medical Genetics Part A, EarlyView.
https://ift.tt/2PSWG8d
Closing a window – opening a door: A response to the letter to the editor
Clinical Anatomy, EarlyView.
https://ift.tt/2PUcJ5T
Country's largest EMS suppliers preps for hurricane response at Central Ohio headquarters
DUBLIN, Ohio — Dublin is home to one of the largest emergency medical suppliers, Bound Tree Medical. Several employees have spent hours making sure its warehouses are stocked with products and supplies now that hurricane Florence has hit, so when first responders hit the ground running, they have what they need. When it comes to hurricanes and other natural disasters, Bound Tree Medical...
https://ift.tt/2xlXADt
Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification
Trisno et al. have generated human esophageal organoids (HEOs) through the directed differentiation of pluripotent stem cells. HEOs contain esophageal progenitors and a differentiated stratified squamous epithelium. Using HEOs to model foregut development revealed that SOX2 regulates NKX2-1 through modulation of Wnt signaling.
https://ift.tt/2QJe6W1
Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells
Skeletal muscle stem cells (MuSCs) in aged animals exhibit a higher incidence of cell death via mitotic catastrophe upon activation, limiting their survival and self-renewal during muscle regeneration. MuSC mitotic catastrophe is regulated by a Notch-p53 axis. Pharmacologic enhancement of p53 levels promotes the survival of aged MuSCs.
https://ift.tt/2xCH0hR
PGC-1α Controls Skeletal Stem Cell Fate and Bone-Fat Balance in Osteoporosis and Skeletal Aging by Inducing TAZ
(Cell Stem Cell 23, 193–209.e1–e5; August 2, 2018)
https://ift.tt/2QMcPNR
3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling
Que, Zhang, and colleagues established an efficient approach to differentiate human pluripotent stem cells (hPSCs) into esophageal progenitor cells (EPCs). Combined use of hPSC-derived EPCs and mouse genetic models demonstrates the important role of BMP and NOTCH signaling in promoting squamous differentiation of EPCs.
https://ift.tt/2xCUcn2
Effects of Acupuncture on the Outcomes of Assisted Reproductive Technology: An Overview of Systematic Reviews
Objectives. To conclude the evidence from systematic reviews (SRs) and meta-analyses assessing the effectiveness of acupuncture to treat couples with subfertility undergoing ART. Methods. We searched the major databases from their inception to March 2018: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP, and Sino-Med (the Chinese database). The primary outcomes of the overview were live birth and clinical pregnancy, and secondary outcomes were ongoing pregnancy, miscarriage, and adverse events. Study selection, quality assessment, and data extraction were performed independently by two review authors. Review methodological quality was assessed by using the AMSTAR tool, and the quality of the evidence was rated by GRADE methods. Results. Eleven systematic reviews were included and published between 2009 and 2017. Our study showed that the acupuncture treatment seems to be a useful tool to improve the clinical pregnancy rate in patients who undergo assisted reproduction therapy. However, there was no evidence that acupuncture had any effect on live birth rate, ongoing pregnancy rates, or miscarriage regardless of whether acupuncture was performed around the time of oocyte retrieval or around the day of embryo transfer; this evidence is inconclusive because of the low quality of the included studies. Conclusions. The evidence for acupuncture to treat couples with subfertility undergoing ART remains unclear. Further research is needed, with high-quality trials undertaken and reported.
https://ift.tt/2QL9PBq
White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease
Abstract
White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter in 64 mutation carriers compared to 45 non-carrier family non-carriers. Using tract-based spatial statistics, we mapped the interaction of mutation status by estimated years from symptom onset on mean diffusivity. For major atlas-derived fibre tracts, we determined the earliest time point at which abnormal mean diffusivity changes in the mutation carriers were detectable. Lastly, we assessed the association between mean diffusivity and cerebrospinal fluid biomarkers of amyloid, tau, phosphorylated-tau, and soluble TREM2, i.e. a marker of microglia activity. Results showed a significant interaction of mutations status by estimated years from symptom onset, i.e. a stronger increase of mean diffusivity, within the posterior parietal and medial frontal white matter in mutation carriers compared with non-carriers. The earliest increase of mean diffusivity was observed in the forceps major, forceps minor and long projecting fibres—many connecting default mode network regions—between 5 to 10 years before estimated symptom onset. Higher mean diffusivity in fibre tracts was associated with lower grey matter volume in the tracts' projection zones. Global mean diffusivity was correlated with lower cerebrospinal fluid levels of amyloid-β1-42 but higher levels of tau, phosphorylated-tau and soluble TREM2. Together, these results suggest that regionally selective white matter degeneration occurs years before the estimated symptom onset. Such white matter alterations are associated with primary Alzheimer's disease pathology and microglia activity in the brain.https://ift.tt/2ppfYqJ
UBA1/GARS-dependent pathways drive sensory-motor connectivity defects in spinal muscular atrophy
Abstract
Deafferentation of motor neurons as a result of defective sensory-motor connectivity is a critical early event in the pathogenesis of spinal muscular atrophy, but the underlying molecular pathways remain unknown. We show that restoration of ubiquitin-like modifier-activating enzyme 1 (UBA1) was sufficient to correct sensory-motor connectivity in the spinal cord of mice with spinal muscular atrophy. Aminoacyl-tRNA synthetases, including GARS, were identified as downstream targets of UBA1. Regulation of GARS by UBA1 occurred via a non-canonical pathway independent of ubiquitylation. Dysregulation of UBA1/GARS pathways in spinal muscular atrophy mice disrupted sensory neuron fate, phenocopying GARS-dependent defects associated with Charcot-Marie-Tooth disease. Sensory neuron fate was corrected following restoration of UBA1 expression and UBA1/GARS pathways in spinal muscular atrophy mice. We conclude that defective sensory motor connectivity in spinal muscular atrophy results from perturbations in a UBA1/GARS pathway that modulates sensory neuron fate, thereby highlighting significant molecular and phenotypic overlap between spinal muscular atrophy and Charcot-Marie-Tooth disease.https://ift.tt/2MRjgw6
A feedback loop between dipeptide-repeat protein, TDP-43 and karyopherin-α mediates C9orf72-related neurodegeneration
Abstract
Accumulation and aggregation of TDP-43 is a major pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 inclusions also characterize patients with GGGGCC (G4C2) hexanucleotide repeat expansion in C9orf72 that causes the most common genetic form of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Functional studies in cell and animal models have identified pathogenic mechanisms including repeat-induced RNA toxicity and accumulation of G4C2-derived dipeptide-repeat proteins. The role of TDP-43 dysfunction in C9ALS/FTD, however, remains elusive. We found G4C2-derived dipeptide-repeat protein but not G4C2-RNA accumulation caused TDP-43 proteinopathy that triggered onset and progression of disease in Drosophila models of C9ALS/FTD. Timing and extent of TDP-43 dysfunction was dependent on levels and identity of dipeptide-repeat proteins produced, with poly-GR causing early and poly-GA/poly-GP causing late onset of disease. Accumulating cytosolic, but not insoluble aggregated TDP-43 caused karyopherin-α2/4 (KPNA2/4) pathology, increased levels of dipeptide-repeat proteins and enhanced G4C2-related toxicity. Comparable KPNA4 pathology was observed in both sporadic frontotemporal dementia and C9ALS/FTD patient brains characterized by its nuclear depletion and cytosolic accumulation, irrespective of TDP-43 or dipeptide-repeat protein aggregates. These findings identify a vicious feedback cycle for dipeptide-repeat protein-mediated TDP-43 and subsequent KPNA pathology, which becomes self-sufficient of the initiating trigger and causes C9-related neurodegeneration.https://ift.tt/2ponYbe
Evidence for peri-ictal blood–brain barrier dysfunction in patients with epilepsy
Abstract
Epilepsy has been associated with a dysfunction of the blood–brain barrier. While there is ample evidence that a dysfunction of the blood–brain barrier contributes to epileptogenesis, blood–brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood–brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood–brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood–brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood–brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood–brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood–brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure.https://ift.tt/2MLZMsB
Endometriosis-associated recto-sigmoid cancer: a case report
Abstract
Background
Endometriosis is a relatively common condition in women of reproductive age. Malignant transformation of intestinal endometriosis is a very rare event. We report a case in which a patient with a history of endometriosis underwent surgery for malignant intestinal endometriosis.
Case presentation
A 55-year-old woman complained of rectorrhagia and intermittent abdominal pain. A neoplasm was revealed by colonoscopy, CT scan and F18-FDG PET/CT of the recto-sigmoidal colon. The patient underwent a rectal anterior resection, hysterectomy and bilateral salpingo-oophorectomy for treatment. According to the histological and immunohistochemical presentation, the diagnosis of endometriosis-associated recto-sigmoid cancer was confirmed. The patient was treated with adjuvant chemotherapy for 6 months. During the follow-up appointment 22 months later, there was clinical and radiographic evidence of recurrence in the rectum. The patient received chemotherapy again and will receive another surgery after two more cycles of chemotherapy.
Conclusion
We report a case of malignant intestinal endometriosis. Although there is no standard therapy for malignant intestinal endometriosis due to the rarity of this disease, surgery and adjuvant chemotherapy seemed to be rational. This case indicates that local recurrence may be a common situation after standard therapy.
https://ift.tt/2NtNMkG
INTEND II randomized clinical trial of intraoperative duct endoscopy in pathological nipple discharge
BJS, EarlyView.
https://ift.tt/2OFMikb
Novel tumor suppressor SPRYD4 inhibits tumor progression in hepatocellular carcinoma by inducing apoptotic cell death
Abstract
Background
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated deaths worldwide. Although recent studies have proposed different biomarkers for HCC progression and therapy resistance, a better understanding of the molecular mechanisms underlying HCC progression and recurrence, as well as the identification of molecular markers with a higher diagnostic accuracy, are necessary for the development of more effective clinical management strategies. Here, we aimed to identify novel players in HCC progression.
Methods
SPRYD4 mRNA and protein expression analyses were carried out on a normal liver-derived cell line (HL-7702) and four HCC-derived cell lines (HepG2, SMMC7721, Huh-7, BEL-7402) using qRT-PCR and Western blotting, respectively. Cell proliferation Cell Counting Kit-8 (CCK-8) assays, protein expression analyses for apoptosis markers using Western blotting, and Caspase-Glo 3/7 apoptosis assays were carried out on the four HCC-derived cell lines. Expression comparison, functional annotation, gene set enrichment, correlation and survival analyses were carried out on patient data retrieved from the NCBI Gene module, the NCBI GEO database and the TCGA database.
Results
Through a meta-analysis we found that the expression of SPRYD4 was downregulated in primary HCC tissues compared to non-tumor tissues. We also found that the expression of SPRYD4 was downregulated in HCC-derived cells compared to normal liver-derived cells. Subsequently, we found that the expression of SPRYD4 was inversely correlated with a gene signature associated with HCC cell proliferation. Exogenous SPRYD4 expression was found to inhibit HCC cell proliferation by inducing apoptotic cell death. We also found that SPRYD4 expression was associated with a good prognosis and that its expression became downregulated when HCCs progressed towards more aggressive stages and higher grades. Finally, we found that SPRYD4 expression may serve as a biomarker for a good overall and relapse-free survival in HCC patients.
Conclusions
Our data indicate that a decreased SPRYD4 expression may serve as an independent predictor for a poor prognosis in patients with HCC and that increased SPRYD4 expression may reduce HCC growth and progression through the induction of apoptotic cell death, thereby providing a potential therapeutic target.
https://ift.tt/2OBYxOx
Genetic deficiency of the tumor suppressor protein p53 influences erythrocyte survival
Abstract
The transcription factor p53 suppresses tumor growth by inducing nucleated cell apoptosis and cycle arrest. Because of its influence on primitive erythroid cell differentiation and survival, p53 is an important determinant of erythropoiesis. However, the impact of p53 on the fate of erythrocytes, cells lacking nucleus and mitochondria, during their post-maturation phase in the circulation remained elusive. Erythrocyte survival may be compromised by suicidal erythrocyte death or eryptosis, which is hallmarked by phosphatidylserine translocation and stimulated by increase of cytosolic Ca2+ concentration. Here, we comparatively examined erythrocyte homeostasis in p53-mutant mice (Trp53tm1Tyj/J) and in corresponding WT mice (C57BL/6J) by analyzing eryptosis and erythropoiesis. To this end, spontaneous cell membrane phosphatidylserine exposure and cytosolic Ca2+ concentration were higher in erythrocytes drawn from Trp53tm1Tyj/J mice than from WT mice. Eryptosis induced by glucose deprivation, a pathophysiological cell stressor, was slightly, but significantly more prominent in erythrocytes drawn from Trp53tm1Tyj/J mice as compared to WT mice. The loss of erythrocytes by eryptosis was fully compensated by enhanced erythropoiesis in Trp53tm1Tyj/J mice, as reflected by increased reticulocytosis and abundance of erythroid precursor cells in the bone marrow. Accordingly, erythrocyte number, packed cell volume and hemoglobin were similar in Trp53tm1Tyj/J and WT mice. Taken together, functional p53 deficiency enhances the turnover of circulating erythrocytes by parallel increase of eryptosis and stimulated compensatory erythropoiesis.
https://ift.tt/2NWwY5o
Central nervous system-predominant Erdheim–Chester disease mimicking meningioma responding to BRAF inhibitor therapy: the importance of molecular diagnosis and targeted therapy in rare neoplastic disorders
Summary
Erdheim–Chester disease (ECD) is a rare multi-system, non-Langerhans cell histiocytic disorder (NLCHD) with only a few hundred cases reported in the literature. Its diverse clinical manifestations require a high level of diagnostic suspicion. BRAFV600E mutation analysis is of critical significance, as it has implications for targeted therapy with BRAF inhibitors such as vemurafenib and dabrafenib. We report a case of symptomatic, central nervous system (CNS)-predominant ECD initially presenting with CNS mass lesions mimicking meningiomas on imaging and prominent periorbital xanthogranulomas. CNS presentation of ECD, although not infrequent, bears particular significance here from a therapeutic point of view, since only partial debulking was possible owing to anatomical complexities. Radiological evaluation following surgery showed no significant change in the size of the lesions. Targeted therapy was commenced following histopathology, immunohistochemistry (IHC), and molecular testing, resulting in marked improvement of clinical symptoms and tumor regression. Thus, diagnostic accuracy was imperative for symptomatic relief in this rare but aggressive neoplasm with a complex clinical presentation and misleading initial radiological impressions, bearing an otherwise grim prognosis.
https://ift.tt/2PS0G98
Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Nikhil Jain, Khaled Himed, Jeffrey M. Toth, Karen C. Briley, Frank M. Phillips, Safdar N. Khan
Abstract
Background Context
Opioid use is prevalent in the management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in vitro, and a previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans.
Purpose
The objective of this work was to study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model.
Study Design/Setting
This is a preclinical animal study.
Materials and Methods
Twenty-four adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received 4 weeks' preoperative and 6 weeks' postoperative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and 4 weeks postoperatively to ensure adequate levels. The control group (n=12) received only perioperative pain control as necessary. All animals underwent a bilateral L5–L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the 6-week postoperative time point, and assessment of fusion was done by manual palpation, plain radiographs, microcomputed tomography (microCT), and histology.
Results
Twelve animals in the control group and 11 animals in the opioid group were available for analysis at the end of 6 weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=.09), a lower trabecular number (p=.02), and a higher trabecular separation (p=.02) compared with the control group. Histologic analysis found areas of incorporation of autograft and unincorporated graft fragments in both groups. In the control group, there was remodeling of de novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de novo woven bone, and hypertrophied osteoblasts were seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histologic findings of relatively immature fusion mass in the opioid group.
Conclusions
Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at 6 weeks in this rabbit spinal fusion model. These preliminary results lay the foundation for further research to investigate underlying cellular mechanisms, the temporal fusion process, and the dose-duration relationship of opioids responsible for our findings.
https://ift.tt/2DhdwfH
Magnetic resonance imaging of the lumbar spine: determining clinical impact and potential harm from overuse
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Nathan M. Wnuk, Tarik K. Alkasab, Daniel I. Rosenthal
Abstract
Background
Lumbar spine magnetic resonance imaging is frequently said to be "overused" in the evaluation of low back pain, yet data concerning the extent of overuse and the potential harmful effects are lacking.
Purpose
The objective of this study was to determine the proportion of examinations with a detectable impact on patient care (actionable outcomes).
Study Design
This is a retrospective cohort study.
Patient Sample
A total of 5,365 outpatient lumbar spine magnetic resonance (MR) examinations were conducted.
Outcome Measures
Actionable outcomes included (1) findings leading to an intervention making use of anatomical information such as surgery; (2) new diagnoses of cancer, infection, or fracture; or (3) following known lumbar spine pathology. Potential harm was assessed by identifying examinations where suspicion of cancer or infection was raised but no positive diagnosis made.
Methods
A medical record aggregation/search system was used to identify lumbar spine MR examinations with positive outcome measures. Patient notes were examined to verify outcomes. A random sample was manually inspected to identify missed positive outcomes.
Results
The proportion of actionable lumbar spine magnetic resonance imaging was 13%, although 93% were appropriate according to the American College of Radiology guidelines. Of 36 suspected cases of cancer or infection, 81% were false positives. Further investigations were ordered on 59% of suspicious examinations, 86% of which were false positives.
Conclusions
The proportion of lumbar spine MR examinations that inform management is small. The false-positive rate and the proportion of false positives involving further investigation are high. Further study to improve the efficiency of imaging is warranted.
https://ift.tt/2NrKSwP
Spine and lower extremity kinematics during gait in patients with cervical spondylotic myelopathy
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Ram Haddas, Sujal Patel, Raj Arakal, Akwasi Boah, Theodore Belanger, Kevin L. Ju
Abstract
Background Context
Cervical spondylotic myelopathy (CSM) typically manifests with a slow, progressive stepwise decline in neurologic function, including hand clumsiness and balance difficulties. Gait disturbances are frequently seen in patients with CSM, with more advanced cases exhibiting a stiff, spastic gait.
Purpose
To evaluate the spatiotemporal parameters and spine and lower extremity kinematics during the gait cycle of adult patients with CSM before surgical intervention.
Study Design
Prospective cohort study.
Patient Sample
Twenty-eight subjects with symptomatic CSM who have been scheduled for surgery and 30 healthy controls (HC).
Outcome Measures
Spine and lower extremity kinematics and spatiotemporal parameters.
Methods
Clinical gait analysis was performed for patients with CSM and HC. The data were analyzed with a one-way analysis of variance.
Results
Patients with CSM have significantly more anterior pelvis tilt (CSM: 13.97°, HC: 5.56°), larger lumbar lordosis (CSM: 8.59°, HC: 2.7°), smaller cervical lordosis (CSM: 6.02°, HC: 11.35°), and less head flexion (CSM: 0.69°, HC: 8.66°) at the beginning of the gait cycle. There was a decrease in knee range of motion in patients with CSM compared with controls (CSM: 36.31°, HC: 50.17°). Furthermore, patients with CSM presented with slower walking speed (CSM: 0.81 m/s, HC: 1.05 m/s), decreased cadence (CSM: 95.57 step/m, HC: 107.64 step/m), increased double support time (CSM: 0.40 s, HC: 0.28 s) and stride time (CSM:1.28 s, HC: 1.13 s), shorter stride length (CSM: 1.04 m, HC: 1.18 m) and step length (CSM:0.51 m, HC: 0.58 m), and wider width (CSM: 0.14 m, HC:0.11 m).
Conclusions
Our study shows that patients with CSM enter the gait cycle with a larger anterior pelvic tilt and lumbar lordosis as well as less cervical lordosis and head flexion. As a consequence of these abnormal spinal parameters at the onset of the gait cycle, lower extremity biomechanics are also altered. Our study is the first to demonstrate the relationship between aberrant spinal alignment and lower extremity function. Identification of this interrelationship as well as the specific gait and biomechanical disturbances seen in myelopathic patients can both inform our understanding of the disease and tailor rehabilitation protocols.
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Biomechanical comparative study of the stability of injectable pedicle screws with different lateral holes augmented with different volumes of polymethylmethacrylate in osteoporotic lumbar vertebrae
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Da Liu, Jun Sheng, Yang Luo, Chen Huang, Hong-Hua Wu, Jiang-Jun Zhou, Xiao-Jun Zhang, Wei Zheng
Abstract
Background Context
Polymethylmethacrylate (PMMA) is widely used for pedicle screw augmentation in osteoporosis. Until now, there had been no studies of the relationship between screw stability and the distribution and volume of PMMA.
Purpose
The objective of this study was to analyze the relationship between screw stability and the distribution pattern and injected volume of PMMA.
Study Design
This is a biomechanical comparison of injectable pedicle screws with different lateral holes augmented with different volumes of PMMA in cadaveric osteoporotic lumbar vertebrae.
Methods
Forty-eight osteoporotic lumbar vertebrae were randomly divided into Groups A, B, and C with different pedicle screws (16 vertebrae in each group), and then each group was randomly divided into Subgroups 0, 1, 2, and 3 with different volumes of PMMA (four vertebra with eight pedicles in each subgroup). A pilot hole was prepared in advance using the same method in all samples. Type A and type B pedicle screws were directly inserted into vertebrae in Groups A and B, respectively, and then different volumes of PMMA (0, 1.0, 1.5, and 2.0 mL) were injected through the screws and into vertebrae in Subgroups 0, 1, 2, and 3. The pilot holes were filled with different volumes of PMMA (0, 1.0, 1.5, and 2.0 mL), and then the screws were inserted in Groups C0, C1, C2, and C3. Screw position and distribution of PMMA were evaluated radiographically, and axial pullout tests were performed to measure maximum axial pullout strength (Fmax).
Results
Polymethylmethacrylate surrounded the anterior one-third of screws in the vertebral body in Groups A1, A2, and A3; the middle one-third of screws in the junction area of the vertebral body and the pedicle in Groups B1, B2, and B3; and the full length of screws evenly in both the vertebral body and the pedicle in Groups C1, C2, and C3. There was no malpositioning of screws or leakage of PMMA in any sample. Two-way analysis of variance revealed that two factors—distribution and volume of PMMA—significantly influenced Fmax (p<.05) but that they were not significantly correlated (p=.088). Fmax values in groups using augmentation with PMMA values significantly improved compared with those in groups without PMMA (p<.05).
Conclusions
Polymethylmethacrylate can significantly enhance the stability of different injectable pedicle screws in osteoporotic lumbar vertebrae, and screw stability is significantly correlated with the distribution pattern and the injected volume of PMMA. The closer the PMMA to the pedicle and the greater the quantity of injected PMMA, the greater is the pedicle screw stability. Injection of 2.0 mL of PMMA through screws with four lateral 180° holes or of 1.0 mL of PMMA through screws with six lateral 180° holes increases the stability of pedicle screws.
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Back pain improves significantly following discectomy for lumbar disc herniation
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): R. Kirk Owens, Leah Y. Carreon, Erica F. Bisson, Mohamad Bydon, Eric A. Potts, Steven D. Glassman
Abstract
Background Context
Although lumbar disc herniation (LDH) classically presents with lower extremity radiculopathy, there are patients who have substantial associated back pain.
Purpose
The present study aims to determine if patients with LDH with substantial back pain improve with decompression alone.
Study Design
This is a longitudinal observational cohort study.
Patient Sample
Patients enrolled in the Quality and Outcomes Database with LDH and a baseline back pain score of ≥5 of 10 who underwent single- or two-level lumbar discectomy only.
Outcome Measures
Back and leg pain scores (0–10), Oswestry Disability Index (ODI), and EuroQoL 5D were measured.
Methods
Standard demographic and surgical variables were collected, as well as patient-reported outcomes at baseline and at 3 and 12 months postoperatively.
Results
The mean age of the cohort was 49.8 years and 1,195 (52.8%) were male. Mean body mass index was 30.1 kg/m2. About half of the patients (1,103, 48.8%) underwent single-level discectomy and the other half (1,159, 51.2%) had two-level discectomy. Average blood loss was 44 cc. Most of the patients (2,217, 98%) were discharged home with routine postoperative care. The average length of stay was 0.53 days. At 3 and 12 months postoperatively, there were statistically significant (p<.000) improvements in back pain (from 7.7 to 2.9 to 3.2), leg pain (from 7.5 to 2.3 to 2.5), and ODI (from 26.2 to 11.6 to 11.2). Patients with a single-level discectomy, compared with patients with a two-level discectomy, had similar improvements in 3- and 12-month back pain, leg pain, and ODI scores.
Conclusions
Patients with LDH who have substantial back pain can be counseled to expect improvement in their back pain scores 12 months after a discectomy.
https://ift.tt/2Dh91S7
Risk factors for perioperative morbidity in spine surgeries of different complexities: a multivariate analysis of 1,009 consecutive patients
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Mazda Farshad, David E. Bauer, Cyrill Wechsler, Christian Gerber, Alexander Aichmair
Abstract
Background Context
There is a broad spectrum of complications during or after surgical procedures, with differing incidences reported in the published literature. Heterogeneity can be explained by the lack of an established evidence-based classification system for documentation and classification of complications in a standardized manner.
Purpose
The objective of this study was to identify predictive risk factors for perioperative and early postoperative morbidities in spine surgeries of different complexities in a large cohort of consecutive patients.
Study Design
This study is a retrospective case series.
Outcome Measures
The outcome measures are the occurrence of perioperative and early postoperative morbidities.
Methods
A classification of surgical complexity (Grades I–III) was created and applied to 1,009 patients who consecutively underwent spine surgery at a single university hospital. The incidence and the type of perioperative and early postoperative morbidities were documented. Multivariate binary logistic regression analyzed risk factors for (1) hospital stay of ≥10 days, (2) intermediate care unit (IMC) stay of ≥24 hours, (3) blood loss of >500 mL, and occurrence of a (4) surgical or (5) medical morbidity.
Results
A deviation from the regular postoperative course (defined as "morbidity") included surgical reasons, such as relapse of symptoms of any kind (3.3%), wound healing problems (2.4%), implant-associated complications (1.6%), postoperative neurologic deficits (1.5%), infection (1.5%), fracture (0.8%), and dural tear in need of revision (0.6%). Medical reasons included anemia (1.8%), symptomatic electrolyte derailment (1.0%), and cardiac complications (0.7%), among others. An independent risk factor associated with a surgical reason for an irregular postoperative course was male gender. Risk factors associated with a medical reason for an irregular postoperative course were identified as preoperatively high creatinine levels, higher blood loss, and systemic steroid use. Independent risk factors for a prolonged hospitalization were preoperatively high C-reactive protein level, prolonged postoperative IMC stay, and revision surgery. Spinal stabilization or fusion surgery, particularly if involving the lumbosacral spine, age, and length of surgery were associated with blood loss of >500 mL. Higher surgical complexity, involvement of the pelvis in instrumentation, American Society of Anesthesiologists Grade ≥III, and preoperatively higher creatinine levels were associated with a postoperative IMC stay of >24 hours.
Conclusions
The present study confirms several modifiable and non-modifiable risk factors for perioperative and early postoperative morbidities in spine surgery, among which surgical factors (such as complexity, revision surgery, and instrumentation, including the pelvis) play a crucial role. A classification of surgical complexity is proposed and validated.
https://ift.tt/2Nqwx3H
Rod fracture in adult spinal deformity surgery fused to the sacrum: prevalence, risk factors, and impact on health-related quality of life in 526 patients
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Thamrong Lertudomphonwanit, Michael P. Kelly, Keith H. Bridwell, Lawrence G. Lenke, Steven J. McAnany, Prachya Punyarat, Timothy P. Bryan, Jacob M. Buchowski, Lukas P. Zebala, Brenda A. Sides, Karen Steger-May, Munish C. Gupta
Abstract
Background Context
Risk factors associated with rod fracture (RF) following adult spinal deformity (ASD) surgery fused to the sacrum remain debatable, and the impact of RF on patient-reported outcomes (PROs) after ASD surgery has not been investigated.
Purpose
We aimed to evaluate the prevalence of and risk factors for RF and determine PROs changes associated with RF after ASD surgery fused to the sacrum.
Study Design/Setting
A retrospective single-center cohort study was performed.
Patient Sample
Patients undergoing long-construct posterior spinal fusions to the sacrum performed at a single institution by two senior spine surgeons from 2004 to 2014 were included.
Outcome Measures
Patient demographics, radiographic parameters, and surgical factors were assessed for risk factors associated with RF. Oswestry Disability Index (ODI) and Scoliosis Research Society-30 (SRS-30) scores were assessed at baseline, 1 year postoperatively, and latest follow-up.
Methods
Inclusion criteria were ASD patients age >18 who had ≥5 vertebrae instrumented and fused posteriorly to the sacrum and either development of RF or no development of RF with minimum 2-year follow-up. Patient characteristics, operative data, radiographic parameters, and PROs were analyzed at baseline and follow-up. Separate Cox proportional hazard models based on rod material and diameter were used to determine factors associated with RF.
Results
Five hundred twenty-six patients (80%) were available for analysis. RF occurred in 97 (18.4%) patients (unilateral RF n=61 [63%]; bilateral RF n=36 [37%]). Risk factors for fracture of 5.5 mm cobalt chromium (CC) instrumentation (CC 5.5 model) included preoperative sagittal vertical axis (hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 1.02–1.14 per 1-cm increase), preoperative thoracolumbar kyphosis (HR 1.02, 95% CI 1.01–1.04 per 1-degree increase), and number of levels fused for patients who received rhBMP-2 <12 mg per level fused (HR 1.48, 95% CI 1.20–1.82 per 1-level increase). Implants that were 5.5-mm CC constructs were at a higher risk for fracture than 6.35-mm stainless steel (SS) constructs (HR 8.49, 95% CI 4.26–16.89). The RF group had less overall improvement in SRS Satisfaction (0.93 vs. 1.32; p=.007) and SRS Self-image domain scores (0.72 vs. 1.02; p=.01). The bilateral RF group had less overall improvement in ODI (8.1 vs. 15.8; p=.02), SRS Subscore (0.51 vs. 0.85; p=.03), and SRS Pain domain scores (0.48 vs. 0.95; p=.02) compared with the non-RF group at final follow-up.
Conclusions
The prevalence of all RF after index procedures was 18.4%, 37% for bilateral RF. Greater preoperative sagittal vertical axis, greater preoperative thoracolumbar kyphosis, increased number of vertebrae fused for patients who received rhBMP-2 <12 mg per level fused, and CC 5.5-mm rod were associated with RF. Less improvement in patient satisfaction and self-image was noted in the RF group. Furthermore, bilateral RF significantly affected PROs as measured by ODI and SRS Subscore at final follow-up.
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Short-term outcomes following posterior cervical fusion among octogenarians with cervical spondylotic myelopathy: a NSQIP database analysis
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Caroline E. Vonck, Joseph E. Tanenbaum, Thomas T. Bomberger, Edward C. Benzel, Jason W. Savage, Iain H. Kalfas, Thomas E. Mroz, Michael P. Steinmetz
Abstract
Background Context
Degenerative changes in the cervical spine occur in an age-dependent manner. As the US population continues to age, the incidence of age-dependent, multilevel, degenerative cervical pathologies is expected to increase. Similarly, the average age of patients with cervical spondylotic myelopathy (CSM) will likely trend upward. Posterior cervical fusion (PCF) is often the treatment modality of choice in the management of multilevel cervical spine disease. Although outcomes following anterior cervical fusion for degenerative disease have been studied among older patients (aged 80 years and older), it is unknown if these results extend to octogenarian patients undergoing PCF for the surgical management of CSM.
Purpose
The present study aimed to quantify surgical outcomes following PCF for the treatment of CSM among the octogenarian patient population compared with patients younger than 80 years old.
Study Design/Setting
This was a retrospective study that used the National Surgical Quality Improvement Program (NSQIP).
Patient Sample
The sample included patients aged 60–89 who had CSM and who underwent PCF from 2012 to 2014.
Outcome Measures
The outcome measures were multimorbidity, prolonged length of stay (LOS), discharge disposition (to home or skilled nursing/rehabilitation facility), 30-day all-cause readmission, and 30-day reoperation.
Methods
The NSQIP database was queried for patients with CSM (International Classification of Disease, Ninth Revision, Clinical Modification code 721.1) aged 60–89 who underwent PCF (Current Procedural Terminology code 22600) from 2012 to 2014. Cohorts were defined by age group (60–69, 70–79, 80–89). Data were collected on gender, race, elective or emergent status, inpatientor outpatient status, where patients were admitted from (home vs. skilled nursing facility), American Society of Anesthesiologists class, comorbidities, and single- or multilevel fusion. After controllingfor these variables, logistic regression analysis was used to compare outcome measures in the different age groups.
Results
A total of 819 patients with CSM who underwent PCF (416 aged 60–69, 320 aged 70–79, and 83 aged 80–89) were identified from 2012 to 2014. Of the PCF procedures, 79.7% were multilevel. There were no significant differences in the odds of multimorbidity, prolonged LOS, readmission, or reoperation when comparing octogenarian patients with CSM with patients aged 60–69 or 70–79. Patients aged 60–69 and 70–79 were significantly more likely to be discharged to home than patients over 80 (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.8–10.4, p<.0001, and OR 2.7, 95% CI 1.1–6.4, p=.0005, respectively).
Conclusions
Compared with patients aged 60–69 and 70–79, octogenarian patients with CSM were significantly more likely to be discharged to a location other than home following PCF. After controlling for patient comorbidities and demographics, 80- to 89-year-old patients with CSM who underwent PCF did not differ in other outcomes when compared with the other age cohorts. These results can improve preoperative risk counseling and surgical decision-making.
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“Microendoscopic” versus “pure endoscopic” surgery for spinal intradural mass lesions: a comparative study and review
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Sivashanmugam Dhandapani, Madhivanan Karthigeyan
Abstract
Background Context
Endoscopy is increasingly being used for minimal invasiveness and panoramic visualization, with unclear efficacy and safety among spinal intradural mass.
Objective
The present study aims to compare microendoscopic and pure endoscopic surgery for spinal intradural lesions.
Materials and methods
Spinal intradural lesions operated using endoscopic or access ports were categorized into "microendoscopic" (predominant microscope use) or "pure endoscopic" (stand-alone endoscopy) surgery, and were studied with respect to clinico-radiological features, techniques, perioperative course, histopathology, clinical, and radiological outcome at minimum of 3 months.
Results
Among 34 patients studied, the initial 15 had "microendoscopic" surgery, 16 had "pure-endoscopic" surgery, and 3 had "mixed" use. There were 18 nerve sheath tumors, 6 meningiomas, 6 cysts, 2 ependymomas, ranging in size from 1.5 to as large as 6.8 cm (21%≥4 cm), including 4 in craniovertebral junction (CVJ). Intermuscular or paraspinous approach was utilized, followed by small bony fenestration or interlaminar corridor. Even larger tumors could be excised using expandable ports or "sliding delivery" technique. Although visualization of sides and angles was better with endoscope, hemostasis and dural closure had steep learning curve, necessitating the use of microscope in the initial cases. Clinical improvement and radiological resolution could be achieved in all. There was no significant difference between the groups. The change in Nurick grade had significant correlation with only the dimension of lesion (p=.03) and preoperative grade (p=.05).
Conclusions
This is probably the first report of spinal endoscopy for intradural tumors in CVJ or as big as 7 cm. Endoscopy is effective and safe for even large tumors with better visualization of sides and angles, albeit with hemostasis and dural closure having initial learning curve. Wide heterogeneity of surgical terminologies in the literature on these procedures warrants consensus for uniform reporting.
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Variation in costs among surgeons for lumbar spinal stenosis
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Paul T. Ogink, Teun Teunis, Olivier van Wulfften Palthe, Karen Sepucha, Christopher M. Bono, Joseph H. Schwab, Thomas D. Cha
Abstract
Background Context
Lumbar spinal stenosis is a common condition in the elderly for which costs vary substantially by region. Comparing differences between surgeons from a single institution, thereby omitting regional variation, could aid in identifying factors associated with higher costs and individual drivers of costs. The use of decision aids (DAs) has been suggested as one of the possible tools for diminishing costs and cost variation.
Purpose
(1) To determine factors associated with higher costs for treatment of spinal stenosis in the first year after diagnosis in a single institution; (2) to find individual drivers of costs for providers with higher costs; and (3) to determine if the use of DAs can decrease costs and cost variability.
Study Design
Retrospective cohort study.
Patient Sample
A total of 10,858 patients in 18 different practices diagnosed with lumbar spinal stenosis between January 2003 and July 2015 in three associated hospitals of a single institution.
Outcome Measures
Mean cost for a patient per provider in US dollars within 1 year after diagnosis of lumbar spinal stenosis.
Methods
We collected all diagnostic testing, office visits, injections, surgery, and occupational or physical therapy related to lumbar spinal stenosis within 1 year after initial diagnosis. We used multivariable linear regression to determine independent predictors for costs. Providers were grouped in tiers based on mean total costs per patient to find drivers of costs. To assess the DAs effect on costs and cost variability, we matched DA patients one-to-one with non-DA patients.
Results
Male gender (β 0.10, 95% confidence interval [CI] 0.05–0.15, p<.001), seeing an additional provider (β 0.77, 95% CI 0.69–0.86, p<.001), and having an additional spine diagnosis (β 0.79, 95% CI 0.74–0.84, p<.001) were associated with higher costs. Providers in the high cost tier had more office visits (p<.001), more imaging procedures (p<.001), less occupational or physical therapy (p=.002), and less surgery (p=.001) compared with the middle tier. Eighty-two patients (0.76%) received a DA as part of their care; there was no statistically significant difference between the DA group and the matched group in costs (p=.975).
Conclusions
Male gender, seeing an additional provider, and having an additional spine diagnosis were independently associated with higher costs. The main targets for cost reduction we found are imaging procedures and number of office visits. Decision aids were not found to affect cost.
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Risk factor analysis of adjacent segment disease requiring surgery after short lumbar fusion: the influence of rheumatoid arthritis
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Jin-Sung Park, Kyu-Dong Shim, Young-Sik Song, Ye-Soo Park
Abstract
Background Context
The influence of rheumatoid arthritis (RA) on the lumbar spine has received relatively little attention compared with cervical spine, and few studies have been conducted for adjacent segment disease (ASD) after lumbar fusion in patients with RA.
Purpose
The present study aims to determine the incidence of ASD requiring surgery (ASDrS) after short lumbar fusion and to evaluate risk factors for ASDrS, including RA.
Study Design
This is a retrospective cohort study.
Patient Sample
The present study included 479 patients who underwent lumbar spinal fusion of three or fewer levels, with the mean follow-up period of 51.2 (12–132) months.
Outcome Measures
The development of ASD and consequent revision surgery were reviewed using follow-up data.
Methods
The ASDrS-free survival rate of adjacent segments was calculated through Kaplan-Meier method. The log-rank test and Cox regression analysis were used to evaluate risk factors comprising RA, age, gender, obesity, osteoporosis, diabetes, smoking, surgical method, and the number of fusion segments.
Results
After short lumbar fusion, revision surgery for ASD was performed in 37 patients (7.7%). Kaplan-Meier analysis predicted that the ASDrS-free survival rate of adjacent segments was 97.8% at 3 years, 92.7% at 5 years, and 86.8% at 7 years. In risk factor analysis, patients with RA showed a 4.5 times higher risk of ASDrS than patients without RA (p<.001), and patients with three-segment fusion showed a 2.7 times higher risk than patients with one- or two-segment fusion (p=.005).
Conclusions
Adjacent segment disease requiring surgery was predicted in 13.2% of patients at 7 years after short lumbar fusion. Rheumatoid arthritis and the number of fusion segments were confirmed as risk factors.
https://ift.tt/2DeTuCr
Percutaneous and open iliac screw safety and accuracy using a tactile technique with adjunctive anteroposterior fluoroscopy
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Stephen G. George, Nathan H. Lebwohl, Giulio Pasquotti, Seth K. Williams
Abstract
Background Context
All currently described percutaneous iliac screw placement methods are entirely dependent on fluoroscopy.
Purpose
The purpose of this study was to determine the safety and the accuracy of percutaneous and open iliac screw placement using a primarily tactile technique with adjunctive anteroposterior (AP) fluoroscopy.
Study Design/Context
All patients who underwent open and percutaneous iliac screw placement over a 5-year period were identified. Charts were reviewed to assess for any instances of neurologic or vascular injury associated with iliac screw placement. Screw accuracy was judged with postoperative computed tomography (CT) scans.
Patient Sample
A total of 133 patients were identified who underwent open or percutaneous iliac screw placement. Computed tomography scans were available for 57 patients, and all of these patients were included in the study, with a total of 115 iliac screws.
Outcome Measures
Radiographic measurements were performed, consisting of the distance of the iliac screw to the sciatic notch on postoperative radiographs and CT scans. Computed tomography scans were used to determine iliac screw accuracy.
Methods
Charts were reviewed to assess for any neurologic or vascular injuries related to screw placement. The distance of the iliac screw to the sciatic notch was measured and compared on AP radiography and CT scans. Computed tomography scans were assessed for any screw violation of the iliac cortex or the sciatic notch. The accuracy of open iliac screw placement was compared with minimally invasive percutaneous placement.
Results
There were no neurologic or vascular injuries related to screw placement in the 133 patients. Computed tomography scans were available for 115 iliac screws, with 3 cortical breaches, all by less than 2 mm. All 112 other screws were accurately intraosseous. There was a strong correlation between the iliac screw to the sciatic notch distance when measured by CT scan compared with AP radiography (r=0.9), thus validating the accuracy of AP fluoroscopy in guiding iliac screw placement with respect to the sciatic notch. Iliac screw accuracy was equal with the open and percutaneous insertion techniques.
Conclusions
The described surgical technique represents a safe and reliable surgical option for iliac screw placement. Intraoperative AP fluoroscopy accurately reflects the distance of the iliac screw to the sciatic notch. Percutaneous iliac screws placed with this technique are as accurate as open iliac screws.
https://ift.tt/2Nn9EhL
Clinical outcomes of percutaneous suction aspiration and drainage for the treatment of infective spondylodiscitis with paravertebral or epidural abscess
Publication date: September 2018
Source: The Spine Journal, Volume 18, Issue 9
Author(s): Tsunemasa Matsubara, Kei Yamada, Kimiaki Sato, Masafumi Gotoh, Kensei Nagata, Naoto Shiba
Abstract
Background Context
Patients with infective spondylodiscitis who failed conservative treatment are generally indicated for open surgery. However, some patients are poor candidates for standard surgery, hence the need to evaluate less invasive approaches. Good outcomes were previously reported for percutaneous suction aspiration and drainage (PSAD) in the treatment of infective spondylodiscitis resistant to conservative therapy. We recently extended the surgical approach of PSAD to allow drainage of paravertebral or epidural abscesses in patients with progressive infective spondylodiscitis.
Purpose
To evaluate the clinical outcomes of PSAD for infective spondylodiscitis with paravertebral or epidural abscess.
Design
Retrospective case series.
Patient Sample
Patients with infective spondylodiscitis and associated epidural or paravertebral abscess treated using PSAD at our institution, between 1998 and 2014.
Outcome Measures
Serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and imaging data obtained via plain radiography, computed tomography, and magnetic resonance imaging were analyzed. Serum measurements were taken preoperatively and at several time points postoperatively. Clinical outcomes were evaluated using the modified MacNab criteria for overall functional mobility.
Methods
Data were obtained from the patients' case notes, radiological images, and medical records. Student t test was used to assess the relevance of changes in serum levels of CRP and ESR at each evaluated time point, as well as the change in sagittal Cobb angle between the preoperative state and the state at final follow-up.
Results
Fifty-two patients (31 men and 21 women; average age, 70.6 years) were included in our analysis. The median (range) CRP levels and ESR values at the time of diagnosis were 6.86 (0.04–20.15) mg/dL and 78.8 (26–120) mm/h, respectively. At 1 year postoperatively, these values had decreased to 0.18 (0.0–1.2) mg/dL and 13.8 (4–28) mm/h for CRP and ESR, respectively. At final follow-up, bone union was observed in 80.8% (42 of 52) of patients, with instability identified in five patients. Regarding functional mobility, excellent outcomes were obtained in 26.9% (14 of 52) of patients, whereas good, fair, and poor outcomes were noted in 42.3% (22 of 52), 3.9% (2 of 52), and 26.9% (14 of 52) of patients, respectively. Overall, treatment was considered effective in 69.2% (36 of 52) of patients.
Conclusions
Percutaneous suction aspiration and drainage can serve as an effective alternative to open surgery for the treatment of patients with progressive infective spondylodiscitis and associated paravertebral or epidural abscess.
https://ift.tt/2Dn22qK
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