bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer
Authors: Belorusova Anna Y , Bourguet Maxime , Hessmann Steve , Chalhoub Sandra , Kieffer Bruno , Cianférani Sarah , Rochel Natacha
Published: September 2020

The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.
A Baker’s Dozen of Top Antimicrobial Stewardship Intervention Publications in 2019
Authors: Stover Kayla R , Chahine Elias B , Cluck David , Green Sarah , Chastain Daniel B , Childress Darrell , Faulkner-Fennell Carmen , Lusardi Katherine , McGee Edoabasi U , Turner Michelle , Bookstaver P Brandon , Bland Christopher M
Published: September 2020

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship–related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one’s institution.
Jasmonic Acid- and Ethylene-Induced Mitochondrial Alternative Oxidase Stimulates Marssonina brunnea Defense in Poplar
Authors: Liao Yangwenke , Cui Rongrong , Xu Xin , Cheng Qiang , Li Xiaogang
Published: September 2020

Mitochondrial processes are implicated in plant response to biotic stress caused by viruses, actinomyces, bacteria and pests, but their function in defense against fungal invasion remains unclear. Here, we investigated the role and regulation of mitochondrial alternative oxidase (AOX) in response to black spot disease caused by the hemibiotrophic fungus Marssonina brunnea in poplar. M. brunnea inoculation induced the transcription of the AOX1a gene in the mitochondrial electron transport chain and of jasmonic acid (JA) and ethylene (ET) biosynthetic genes, with the accumulation of these phytohormones in poplar leaf, while inhibiting the transcript amount of the mitochondrial cytochrome c oxidase gene (COX6b) and genes related to salicylic acid (SA). Enhanced AOX reduced poplar susceptibility to M. brunnea with a higher ATP/ADP ratio while the repressed AOX caused the reverse effect. Exogenous JA and 1-aminocyclopropane-1-carboxylic acid (ACC, a biosynthetic precursor of ET) inhibited the transcript amount of COX6b and consequently increased the ratio of AOX pathway to total respiration. Furthermore, the transcription of CYS C1 and CYS D1 genes catalyzing cyanide metabolism was induced, while the cysteine (CYS) substrate levels reduced upon M. brunnea inoculation; exogenous JA and ACC mimicked the effect of M. brunnea infection on cysteine. Exogenous SA enhanced, while JA and ACC reduced, poplar susceptibility to M. brunnea. Moreover, inhibiting AOX completely prohibited JA- and ET-increased tolerance to M. brunnea in poplar. These observations indicate that the JA- and ET-induced mitochondrial AOX pathway triggers defense against M. brunnea in poplar. This effect probably involves cyanide. These findings deepen our understanding of plant–pathogenic fungi interactions.
Size-mediated temperature effect on embryonic development in Eodiaptomus japonicus (Copepoda, Calanoida) in Lake Biwa, Japan
Authors: Liu Xin , Ban Syuhei
Published: September 2020

Egg size has numerous ecological implications for zooplankton, and can influence hatching duration and female fecundity. In this study, temperature functions of embryonic development time (EDT) were determined in the copepod Eodiaptomus japonicus from Lake Biwa, in the cold and warm seasons, to clarify synergistic effects of egg size and temperature on EDT. EDT was longer for cold season eggs than warm ones, but both seasons were well fitted by Bĕlehrádek’s function. Egg size was significantly correlated with female body size within seasons, but the relationship did not differ significantly between seasons. These results suggest that seasonal variation in EDT, which was associated with egg size, may result from temperature-mediated variation of female body size, because larger females produced larger eggs as temperature decreased. Larger eggs may enhance fitness under severe food conditions in winter due to high hatchability and naupliar survival.
Exploring Patient Perceptions of Opioid Treatment Agreements in a Community Health Center Environment
Authors: Irwin Adriane N , Braden-Suchy Natalea , Hartung Daniel M
Published: September 2020

Objective

Describe patient attitudes toward opioid treatment agreements (OTAs) and characterize perceptions of their impact on patient care, behavior, communication with prescribers, and engagement with the health care system.

Design

Qualitative descriptive study.

Setting

Federally qualified health center with six clinic locations serving a rural population.

Subjects

Patients were prescribed long-term opioid therapy and were required to sign an OTA through an in-person office visit with a clinical pharmacist.

Methods

Patients who signed an OTA were recruited to participate in semistructured, in-person, one-on-one interviews. Data were analyzed using immersion-crystallization methods.

Results

Among the 20 patients recruited, 50% were men; 70% were insured by the state’s Medicaid program; and 85% were using opioids for hip, back, and/or neck pain. Four major themes arose from the interviews. First, individuals who use long-term opioids experience a wide variety of opioid-related fears and stigmas. Second, individuals articulated real or potential benefits from implementing OTAs. Third, opinions differed on whether OTAs affected behavior and reduced opioid misuse and diversion. Finally, individuals provided feedback on the health care system’s OTA implementation process.

Conclusions

Patients experienced a wide variety of opioid-related fears and stigmas, including how OTA requirements can perpetuate these issues. Despite these feelings, participants articulated real or potential positive outcomes from the use of OTAs, although they were mixed on whether these agreements translated to any behavior changes. If OTAs are to become standard practice, future research is needed to describe the diversity of patient perspectives and experiences with OTAs and to evaluate their effect on patient outcomes.
Integrating Symptoms Into the Diagnostic Criteria for Breast Cancer–Related Lymphedema: Applying Results From a Prospective Surveillance Program
Authors: Brunelle Cheryl L , Roberts Sacha A , Horick Nora K , Gillespie Tessa C , Jacobs Jamie M , Daniell Kayla M , Naoum George E , Taghian Alphonse G
Published: September 2020

Objective

The objectives of this study were to determine whether patients reporting symptoms are more likely to develop lymphedema and to describe the temporal relationship between symptom onset and lymphedema.

Methods

This was a prospective longitudinal cohort study of 647 women treated for breast cancer and screened for lymphedema using arm volume measurements and subjective questionnaires (n = 647; 2284 questionnaires [median 3.5 per patient, range = 1–24]). Primary study outcome was lymphedema (relative volume change ≥10%). The Kaplan–Meier method was used to estimate cumulative lymphedema incidence. Cox proportional hazards models were used to assess the relationship between symptoms, other risk factors, and lymphedema.

Results

A total of 64 patients (9.9%) developed lymphedema. On multivariable analysis, patients reporting increased arm size (hazard ratio = 3.09, 95% CI = 1.62–5.89) were more likely to progress to lymphedema than those who did not report this symptom. Of those who developed lymphedema, 37 (58%) reported an increased arm size a median of 6.1 months before lymphedema onset (range = 68.6 months before to 50.2 months after lymphedema onset).

Conclusion

Patients at risk of lymphedema who report increased arm size might do so prior to lymphedema onset and are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without objective or observable edema, these patients should be followed vigilantly and considered for early intervention. Symptoms should be incorporated into screening and diagnostic criteria for lymphedema.

Impact

This study shows that patients at risk for breast cancer–related lymphedema who report increased arm size should be considered at high risk for progression to lymphedema—even without edema on measurement or clinical examination—and should be followed vigilantly, with consideration of early intervention.

Lay summary

If you are at risk of lymphedema and you feel as though your arm size has increased, you might develop lymphedema, and you are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without measurable or observable edema, you should be followed vigilantly and consider early intervention.
Heterogeneous impacts of research grant funding
Authors: Bloch Carter
Published: September 2020

This paper seeks to examine whether there is heterogeneity in the impacts of research grant funding, by examining whether before–after differences in citation impact are related to the past performance of grantees. Analysis of the heterogeneity in funding impacts can potentially inform the selection of awardees and the design of funding instruments and application and assessment procedures. We examine the impacts of research project grants awarded over the period from 2005 to 2008 from the Danish Council for Independent Research. For the matched sample of grantees and rejected applicants, mean before–after differences are significantly greater for grantees than rejected applicants. However, results are more mixed when comparing overall distributions instead of mean values, where results are either not significant or weakly significant at the 10% level. This suggests that grants lead to strong results for some but are much less for the majority of grantees. The analysis finds indications that citation impact of research grants is positively related to past research performance, thus providing indications of heterogeneity in grant effects. Additional work could be very useful in further exploring possible systematic relationships between other applicant characteristics, such as years of experience as a researcher and overall publication activity, and subsequent impacts.
A Model of Relative Thinking
Authors: Bushong Benjamin , Rabin Matthew , Schwartzstein Joshua
Published: September 2020

Fixed differences loom smaller when compared to large differences. We propose a model of relative thinking where a person weighs a given change along a consumption dimension by less when it is compared to bigger changes along that dimension. In deterministic settings, the model predicts context effects such as the attraction effect but predicts meaningful bounds on such effects driven by the intrinsic utility for the choices. In risky environments, a person is less likely to sacrifice utility on one dimension to gain utility on another that is made riskier. For example, a person is less likely to exert effort for a fixed monetary return if there is greater overall income uncertainty. We design and run experiments to test basic model predictions and find support for these predictions.
Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren’s syndrome
Authors: Jimenez-Royo Pilar , Bombardieri Michele , Ciurtin Coziana , Kostapanos Michalis , Tappuni Anwar R , Jordan Natasha , Saleem Azeem , Fuller Teresa , Port Kathleen , Pontarini Elena , Lucchesi Davide , Janiczek Robert , Galette Paul , Searle Graham , Patel Neel , Kershaw Lucy , Gray Calum , Ratia Nirav , van Maurik André , de Groot Marius , Wisniacki Nicolas , Bergstrom Mats , Tarzi Ruth
Published: September 2020

Objectives

To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes.

Methods

In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored.

Results

Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration.

Conclusion

Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.
BENCHMARKING THE DOSE MAP SOFTWARE FOR CLINICAL IMPLEMENTATION AND ESTABLISHMENT OF A LOCAL FOLLOW-UP PROTOCOL FOR THE MANAGEMENT OF SKIN INJURES FOLLOWING COMPLEX INTERVENTIONAL CARDIOLOGY PROCEDURES
Authors: Rizk Chadia , Sarkis Antoine , Bejjani Alice , Dabin Jérémie , Farah Jad
Published: September 2020

This paper aims to validate the accuracy of the peak skin dose (Dskin,max) computed by the Dose Map software (DMS)—general electric and establish a local follow-up protocol for the management of patient skin injuries following complex interventional cardiology procedures (ICPs). Dskin,max was computed by the DMS and was simultaneously measured by a dense mesh of 72 thermoluminescent dosemeters for 20 ICP. Measured and computed Dskin,max were compared using Lin’s concordance coefficient (${\rho}_c$). The implementation of a local follow-up strategy was based on a computed Dskin,max of 2 Gy. After eliminating 2 outliers, the average deviation between the two methods was 6% (range: −36 to +40%). Concordance between the two methods was moderate with ${\rho}_c$ (confidence interval) of 0.9128 (0.8541–0.9486). DMS computes Dskin,max with an acceptable accuracy and can be used to setup an individual follow-up process for patients with high skin exposure and risks.
Overlapping certification and technical efficiency of ICT convergence companies in South Korea
Authors: Kim Kyunam , Choe Chung , Lee Daeho
Published: September 2020

Since the late 1990s, in South Korea, two innovation certification policies—InnoBiz and Venture certifications—have fostered the innovation activities of venture companies and small- to medium-sized enterprises.The two certifications, however, share similar features in their policy goals, targets, and main content. This study aims to evaluate how technical efficiencies of firms differ based on the types of innovation certifications it achieves and examine the result when a firm simultaneously achieves overlapping certifications. We classified information and communication technology convergence firms into four different groups by certification type and evaluated their performance based on technical efficiency (TE) by applying stochastic frontier analysis and meta-frontier analysis. Our results show that the meta-frontier TE of the group with overlapping certifications is lower than that of the group with a single certification, implying that there is no remarkable performance improvement in terms of the efficiency, particularly when certifications sharing similar characteristics are implemented.
Severe Malnutrition and Anemia Are Associated with Severe COVID in Infants
Authors: Kulkarni Rajesh , Rajput Uday , Dawre Rahul , Sonkawade Naresh , Pawar Sameer , Sonteke Somendra , Varvatte Balaji , Aathira K C , Gadekar Kailas , Varma Santosh , Nakate Leena , Kagal Anju , Kinikar Aarti
Published: September 2020

Background

COVID-19 is uncommon and less severe in children than adults. It is thought that infants may be at higher risk for severe disease than older children. There is a paucity of literature on infants with COVID, particularly those with severe disease.

Objective

We describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of infants with confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India

Methodology

Infants who tested positive for SARS-CoV-2 and were admitted between 1 April 2020 and 7 August 2020 were included in the study.

Results

A total of 13 infants were admitted during the study period. The median age was 8 months (IQR 6) and nine were male. Common presenting features were fever (n = 8, 62%), poor feeding, irritability, and runny nose (n = 3, 23%). Comorbidities noted were severe acute malnutrition (SAM) in three cases (23%) and nutritional megaloblastic anemia, iron deficiency anemia, sickle thalassemia and renal calculi in one case (8%) each. There was a history of low birth weight in two cases (15%). Pallor was noted in three cases (23%), SAM in three cases (23%) and tachypnea and respiratory distress in four cases (30%). Severe anemia, thrombocytopenia, elevated ferritin, abnormal procalcitonin, abnormal C Reactive Protein and deranged D-dimer was noted in three cases (23%) each. Neutrophil–lymphocyte ratio was normal in all cases. Three infants (43%) had evidence of pneumonia on the chest radiograph, of which one had adult respiratory distress syndrome (ARDS) like pattern, one infant had cardiomegaly and perihilar infiltrates. Hydroxychloroquine and azithromycin were given to five patients (38%), Intravenous Immunoglobulin and methylprednisolone were administered to one patient (8%). One infant died of ARDS with multi-organ dysfunction with refractory shock and hemophagocytic lymphohistiocytosis.

Conclusion

SAM and anemia may be associated with severe COVID in infants.
Fungicide Sensitivity Survey of Plasmopara viticola Populations in Georgia Vineyards
Authors: Campbell Sarah E. , Brannen Phillip M. , Scherm Harald , Brewer Marin T.
Published: September 2020

Grapevine downy mildew, caused by Plasmopara viticola, is among the most damaging diseases of grapes globally and in the viticultural regions of Georgia (U.S.A.). Although management of this disease typically involves fungicide applications, resistance development in P. viticola can render chemical management ineffective. The objective of this study was to survey fungicide sensitivities of P. viticola populations in vineyards across three regions in Georgia. Samples were collected from eight vineyards in 2017 and four in 2018 and tested phenotypically for sensitivity to quinone outside inhibitor (QoI), carboxylic acid amide (CAA), and phenylamide (PA) fungicides using leaf disc bioassays. In addition, DNA was extracted from P. viticola samples collected from 2015 through 2018 in these 12 vineyards and six others for a total of 18 vineyards sampled. All available DNA samples were tested for the presence of the known resistance-causing mutations G143A (QoI) and G1105S (CAA) using polymerase chain reaction (PCR). This study documented widespread occurrence of QoI resistance in P. viticola in Georgia, with 83.0% of isolates collected in 2017 and 2018 testing positive for QoI resistance based on bioassay and 82.9% of isolates collected from 2015 to 2018 testing positive for QoI resistance through PCR testing. In total, 94.4% (17/18) of surveyed vineyards had confirmed QoI resistance by the conclusion of the survey period. No reduced sensitivity to CAA or PA fungicides was identified. Due to widespread QoI resistance, these fungicides should not be relied upon for downy mildew management in Georgia vineyards with a long history of their use.
Eosinophilic esophagitis as a complication of food oral immunotherapy
Authors: Jin Hope , Trogen Brit , Nowak-Wegrzyn Anna
Published: September 2020

Purpose of review

Food oral immunotherapy (OIT) has emerged as way to mitigate serious allergic reactions including life-threatening anaphylaxis related to accidental ingestion. However, gastrointestinal-related adverse effects of OIT have been reported and are often cited as reasons for discontinuation of therapy. We summarize recent research on the prevalence of eosinophilic esophagitis (EoE) in patients undergoing OIT.

Recent findings

We examined 12 recent studies on OIT for peanut, milk, walnut, egg, and wheat, which enrolled a total of 620 patients. Gastrointestinal symptoms were common during OIT, and while generally mild, 24 (3.9%) patients from the reviewed studies reported gastrointestinal symptoms that were significant enough to prompt discontinuation of OIT. Of these, two (0.3% of the total 620 patients or 8.3% of those with gastrointestinal symptoms) patients had biopsy-confirmed EoE. One of these patients was subsequently found to also have ulcerative colitis that had been previously undiagnosed.

EoE is a rare but concerning side effect of OIT. More research is needed to better elucidate both the OIT-related and patient-related factors that may predispose individuals to develop EoE. The presence of comorbid conditions and/or preexisting subclinical esophageal eosinophilia may account for some of cases of EoE identified during OIT.
Suicide Probability Among Tramadol Addicts
Authors: Saad Mohamed Ahmed , Ibrahim Nesreen M. , Mazloum Ayat , Naguib Rehab M. , Azzam Lobna
Published: September 2020

Objectives:

Tramadol addiction is one of the major addiction problems in growing countries, especially in Egypt. Moreover, there is a strong relation between suicidality and addiction even after exclusion of personality disorders; the burden of suicide adds to the burden of substance abuse in those individuals and their families.

Materials and Methods:

A cross-sectional descriptive study was conducted on 72 tramadol-dependent patients who were recruited randomly in this study from the addiction outpatient clinic of Okasha Institute of Psychiatry of Ain Shams University, after obtaining an informed consent. They are assessed by (1) Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders for diagnosis of substance use disorder, (2) Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis II Disorders for exclusion of personality disorders, (3) suicide probability scale, and (4) Addiction Severity Index.

Results:

Regarding suicidal probability, 44.44% of the sample showed risk of suicide, which was severe among 19.44%, moderate among 11.11%, and mild among 13.89% of the sample. Regarding “Addiction Severity Index,” most patients had no real medical problem. In the employment domain, 38.89% had a slight problem. In the drug use domain, 80.56% had a moderate problem.

There is a significant relation between the degree of medical, drug use, and legal problem and the severity of suicidal risk. Moreover, the longer duration of addiction and the advanced age of patients are risk factors for suicidal probability.

Conclusions:

There is a suicide probability among tramadol addicts. The duration of tramadol use could be considered a strong risk factor for suicide, as the longer the duration of tramadol, the higher the suicidal risk.
Risk Factors for Increased Postoperative Pain and Recommended Orderset for Postoperative Analgesic Usage
Authors: Armstrong April D. , Hassenbein Susan E. , Black Sarah , Hollenbeak Christopher S.
Published: September 2020

Objective:

An interdisciplinary pain team was established at our institution to explore options for improving pain control in patients undergoing orthopedic surgery by identifying traits that put a patient at increased risk for inadequate pain control postoperatively.

Materials and Methods:

The interdisciplinary pain team identified 7 potential risk factors that may lead to inadequate pain control postoperatively including (1) history of physical, emotional, or sexual abuse; (2) history of anxiety; (3) history of drug or alcohol abuse; (4) preoperative nonsteroidal anti-inflammatory drug, or disease-modifying antirheumatic drug use; (5) current opioid use; (6) psychological conditions other than anxiety; and (7) current smoker. Statistical analysis determined which risk factors were associated with increased preoperative and postoperative pain scores.

Results:

A total of 1923 patients undergoing elective orthopedic surgery were retrospectively identified. Hip, knee, and shoulder replacements accounted for 76.0% of the procedures. 78.5% of patients had 3 or fewer risk factors and 17.1% had no risk factors. Anxiety, other psychological conditions, current opioid use, and current smoking were significantly associated with higher preoperative and postoperative pain scores.

Discussion:

We found a significant association between anxiety, current smoking, psychological conditions, and current opioid use with increased preoperative and postoperative reported pain score. We propose that identification of these risk factors should prompt more attention to postoperative pain control plans and will improve communication with patients and providers. We recommend a multimodal approach to postoperative pain control, and developed a pain orderset to help guide providers.
Vancomycin Powder Use in Fractures at High Risk of Surgical Site Infection
Authors: Qadir Rabah , Costales Timothy , Coale Max , Mulliken Alexandra , Zerhusen Timothy , Joshi Manjari , Castillo Renan C. , Carlini Anthony R. , O'Toole Robert V.
Published: September 2020

Objectives:

To determine if the use of intrawound vancomycin powder reduces surgical-site infection after open reduction and internal fixation of bicondylar tibial plateau, tibial pilon, and calcaneus fractures.

Design:

Retrospective analysis.

Setting:

Level I trauma center.

Patients:

All fractures operatively treated from January 2011 to February 2015 were reviewed; 583 high-risk fractures were included, of which 35 received topical vancomycin powder. A previously published prospectively collected cohort of 235 similar high-risk fractures treated at our center from 2007 through 2010 served as a second comparison group.

Intervention:

Topical vancomycin powder at wound closure.

Main Outcome Measurements:

Deep surgical-site infection. Analyses used both univariate comparison of all patients and 1:2 matching analysis using both nearest neighbor and propensity-based matching.

Results:

Compared with a control group of fractures treated during the same time period without vancomycin powder, the infection rate with vancomycin powder was significantly lower [0% (0/35) vs. 10.6% (58/548), P = 0.04]. Compared with our previously published historical infection rate of 13% for these injuries, vancomycin powder was also associated with significantly decreased deep surgical-site infection (0% vs. 13%, P = 0.02). These results agreed with the matched analyses, which also showed lower infection in the vancomycin powder group (0% vs. 11%–16%, P ≤ 0.05).

Conclusions:

Vancomycin powder may play a role in lowering surgical-site infection rates after fracture fixation. A larger randomized controlled trial is needed to validate our findings.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Fate of Patients After a Staged Nonunion Procedure for Known Infection
Authors: Zhang Joanne Y. , Tornetta Paul , Dale Kevin M. , Jones Clifford B. , Mullis Brian H. , Egol Kenneth A. , Robinson Elliot , Bosse Michael J. , Schmidt Andrew H. , Hymes Robert A.
Published: September 2020

Objectives:

To determine the factors associated with successful union and eradication of infection in the setting of staged procedures to treat obviously infected nonunions of long bones. We hypothesize that patients with positive intraoperative cultures obtained at the time of definitive surgery for infected nonunions are more likely to have persistent nonunion than those with negative cultures.

Design:

Multicenter retrospective review.

Setting:

Eight academic Level 1 trauma centers.

Patients/Participants:

Patients who underwent staged management for obviously infected nonunion of a long bone.

Main Outcome Measurements:

For each patient, initial fracture management, management of retained implants, number of debridements, grafting, bacteriology, antibiotic course, bone defect management, soft-tissue coverage, and definitive surgery performed were reviewed.

Results:

A total of 134 patients were treated with staged procedures for obviously infected nonunion of a long bone (mean age 49 years, 60% open fractures, and mean follow-up 22 months). During definitive procedures, 120 patients had intraoperative cultures taken with 43% having positive cultures. For culture-positive patients, 41 patients achieved eventual union and 10 had persistent nonunion. Of 69 culture-negative patients, 66 achieved eventual union and 3 had persistent nonunion. The number of patients with union versus persistent nonunion was statistically significant between culture-positive and culture-negative groups (P = 0.015).

Conclusions:

Management of infected nonunion in long bones with staged treatments before definitive fixation are beneficial but ultimately less effective when performed in the setting of positive bacterial cultures at the time of definitive management.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Evaluation of RAS mutational status through BEAMing assay to monitor disease progression of metastatic colorectal cancer: a case report
Authors: Lastraioli Elena , Lavacchi Daniele , Palmieri Valeria Emma , Castiglione Francesca , Messerini Luca , Di Costanzo Francesco , Antonuzzo Lorenzo
Published: September 2020

Since the introduction of antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (moAbs), the treatment of metastatic colorectal cancer (mCRC) has become crucially dependent on the mutation profile of the tumour over the last two decades. Recently, rechallenge strategy with cetuximab-based chemotherapy has demonstrated to be active in a subgroup of patients whose tumour maintained wild-type RAS and RAF status. In this setting, liquid biopsy may replace tissue sample for the identification of specific subgroups of pretreated patients that may benefit from the reintroduction of anti-EGFR moAbs. In November 2014, a 64-year-old man with IVB stage BRAF, KRAS and NRAS wild-type mCRC was admitted in our hospital. He received FOLFIRI cetuximab as first-line treatment with deep and long-lasting partial response (PR), followed by cetuximab maintenance therapy until January 2016. At the time of disease progression, FOLFIRI cetuximab regimen was reintroduced resulting in stabilization of disease and he continued with capecitabine cetuximab therapy until disease progression in October 2016. Then, the patient consecutively received FOLFOX bevacizumab, TAS-102, regorafenib and FOLFIRI followed by de Gramont maintenance treatment. Finally, he was retreated with FOLFIRI cetuximab with disease progression within 3 months and died in May 2019. During his clinical course, liquid biopsy detected two mutations: one in KRAS Cd.12 and one in NRAS Cd. 61. The longitudinal assessment of RAS status offers considerable advantages in order to avoid side effects and economic costs for ineffective treatment choices. Liquid biopsy could help better monitor the disease and provide molecularly guided treatments.
Down-regulation of miR-155 inhibits inflammatory response in human pulmonary microvascular endothelial cells infected with influenza A virus by targeting sphingosine-1-phosphate receptor 1
Authors: Shen Si-Mei , Jiang Hao , Zhao Jiang-Nan , Shi Yi
Published: September 2020

Background:

Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.

Methods:

Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.

Results:

MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.

Conclusion:

MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.
Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis
Authors: Cai Xian-Lei , Li Xue-Ying , Liang Chao , Xu Yuan , Zhang Miao-Zun , Yu Wei-Ming , Li Xiu-Yang
Published: September 2020

Background

Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection.

Methods

The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results.

Results

A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = –27.1 min, 95% confidence interval [CI]: –40.8 min to –13.4 min) and lengths of hospital stay (WMD = –1.43 d, 95% CI: –2.31 d to –0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 – 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 – 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = –41.03 min, 95% CI: –59.53 min to –22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 – 10.34).

Conclusions

In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.
Patient satisfaction with intravenous regional anaesthesia or an axillary block for minor ambulatory hand surgery
Authors: Teunkens An , Vermeulen Kristien , Belmans Ann , Degreef Ilse , Van de Velde Marc , Rex Steffen
Published: September 2020

BACKGROUND

Intravenous regional anesthesia (IVRA) and the axillary brachial plexus block are popular alternatives to general anaesthesia in ambulatory hand surgery. Although both have proven their effectiveness, patients’ preferences have never been evaluated.

OBJECTIVES

We investigated patient satisfaction with both techniques and hypothesised that satisfaction after IVRA is noninferior compared with axillary brachial plexus block.

DESIGN

A prospective, randomised controlled trial.

SETTING

Ambulatory surgical day care centre, University Hospitals of Leuven, Belgium, from September 2016 to November 2017.

PATIENTS

One hundred and twenty adults undergoing minor ambulatory hand surgery were included in this study.

INTERVENTION

Patients received either IVRA with 300 mg lidocaine or an axillary block with 280 mg mepivacaine.

MAIN OUTCOME MEASURES

The primary endpoint was the evaluation of patient satisfaction using the ‘Evaluation du Vécu de l’Anésthesie Locoregional’ (EVAN-LR) questionnaire. Secondary outcomes included different procedural times, block quality, tourniquet discomfort, the incidence of block failure and postoperative nausea and vomiting (PONV), the severity of postoperative pain and the need for postoperative analgesics during the first 24 h.

RESULTS

Noninferiority of IVRA was shown for the median [IQR] total score on the EVAN-LR questionnaire, IVRA-group: 92 [87 to 96] vs. axillary brachial plexus block-group: 91[87 to 97]; Hodges--Lehmann estimator (95% confidence interval (CI)] for the shift: −0.25 (−2.60 to 2.20). Induction of anaesthesia and time to discharge, requiring partial recovery of the motor block, were significantly longer in the axillary brachial plexus block group. The IVRA-group had a lower block quality, a higher incidence of tourniquet-discomfort and higher median intra-operative and postoperative pain scores on day 0; 0 [0 to 2] vs. 0 [0 to 0] and 0.8 [0 to 1.8] vs. 0 [0 to 0.25], respectively, but no increase in the need for supplementary analgesics or conversion rate to general anaesthesia.

CONCLUSION

IVRA and axillary brachial plexus block result in comparably high patient satisfaction in ambulatory hand surgery.

CLINICAL TRIAL REGISTRATION

EudraCT 2016-002325-11.
Relationship between psychological factors and spinal motor behaviour in low back pain: a systematic review and meta-analysis
Authors: Christe Guillaume , Crombez Geert , Edd Shannon , Opsommer Emmanuelle , Jolles Brigitte M. , Favre Julien
Published: September 2020

This meta-analysis investigated whether more negative psychological factors are associated with less spinal amplitude of movement and higher trunk muscle activity in individuals with low back pain. Furthermore, it examined whether pain intensity was a confounding factor in this relationship. We included studies that provided at least 1 correlation coefficient between psychological (pain-related fear, catastrophizing, depression, anxiety, and self-efficacy) and spinal motor behaviour (spinal amplitude and trunk muscle activity) measures. In total, 52 studies (3949 participants) were included. The pooled correlation coefficients (95% confidence interval; number of participants) were −0.13 (−0.18 to −0.09; 2832) for pain-related fear, −0.16 (−0.23 to −0.09; 756) for catastrophizing, −0.08 (−0.13 to −0.03; 1570) for depression, −0.08 (−0.30 to 0.14; 336) for anxiety, and −0.06 (−0.46 to 0.36; 66) for self-efficacy. The results indicated that higher levels of pain-related fear, catastrophizing, and depression are significantly associated with reduced amplitudes of movement and larger muscle activity and were consistent across subgroup and moderation analyses. Pain intensity did not significantly affect the association between these psychological factors and spinal motor behaviour and had a very small independent association with spinal motor behaviour. In conclusion, the very small effect sizes found in the meta-analyses question the role of psychological factors as major causes of spinal movement avoidance in low back pain. Experimental studies with more specific and individualized measures of psychological factors, pain intensity, and spinal motor behaviour are recommended.
Prevalence of glaucoma in the elderly population in Taiwan: The Shihpai Eye Study
Authors: Kuo Che-Yuan , Ko Yu-Chieh , Kuang Tung-Mei , Chou Pesus , Chiou Shih-Hwa , Liu Catherine Jui-Ling
Published: September 2020

Background:

This study aimed to evaluate the prevalence, characteristics, and the awareness status of glaucoma in an elderly Chinese population.

Methods:

A total of 460 individuals aged ≥72 years were enrolled in this cross-sectional community-based eye disease screening program. Glaucoma was diagnosed according to the diagnostic criteria proposed by the International Society of Geographical and Epidemiological Ophthalmology. Characteristics of subjects with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) were described and compared between groups using Mann-Whitney U and Fisher’s exact tests.

Results:

Forty subjects were diagnosed with glaucoma, including 17 subjects with POAG, 22 with PACG, and one with secondary glaucoma. The estimated prevalence of glaucoma, POAG, and PACG was 8.7%, 3.7%, and 4.8%, respectively. In total, 71% of the subjects with PACG and 77% of POAG subjects presented with a normal intraocular pressure (IOP) of <19 mmHg. The demographic and ocular characteristics were similar between the two groups; however, subjects with POAG had a longer axial length and smaller vertical disc diameter than those with PACG. Further, 95% of the glaucoma subjects ever visited the eye clinic, but only 32.5% of them were aware of the disease.

Conclusion:

Glaucoma is prevalent in the elderly population in Taiwan, but the diagnostic rate and disease awareness are low. Since most subjects with glaucoma presented with normal IOPs, optic disc evaluation is critical for diagnosing glaucoma in the elderly in Taiwan
The clinical outcomes of elderly esophageal cancer patients who received definitive chemoradiotherapy
Authors: Lu Hao-Wei , Chen Chien-Chih , Chen Hsin-Hua , Yeh Hui-Ling
Published: September 2020

Background:

Neoadjuvant chemoradiotherapy (CRT) followed by an esophagectomy is the standard treatment for locally advanced esophageal cancer, but remains a great challenge for elderly patients. Therefore, we aim to evaluate the efficacy of definitive CRT in elderly patients with esophageal cancer.

Methods:

From December 2007 to October 2017, 40 esophageal cancer patients aged ≥70 years receiving definitive CRT were retrospectively analyzed. All patients received cisplatin-based chemotherapy. Ten patients received standard doses of cisplatin 20 mg/m2 and fluorouracil (5-FU) 800 mg/m2 for 4 days, during the first and fifth weeks of radiotherapy. Eighteen patients received modified doses of cisplatin 16 to 18 mg/m2 and 5-FU 600 to 800 mg/m2. Twelve patients received lower doses of cisplatin 10 to 12 mg/m2 and 5-FU 400 to 600 mg/m2. The endpoints were overall survival (OS), tumor response rate, and treatment compliance.

Results:

The 3-year OS rate was 28.8% The 3-year OS rates for patients receiving standard, modified, and lower doses were 12.5%, 53.8%, and 0.0%, respectively (p = 0.05). There were 87.5% of patients completing the scheduled radiotherapy dose, along with two cycles of concurrent chemotherapy. The response rate (clinical complete response and partial response rate) was 70.0%. Multivariate analysis revealed that no statistical difference was found in the OS among three groups of chemotherapy dosage. The treatment response was the only independent prognostic factor to OS (p < 0.001).

Conclusion:

Definitive CRT with dose modification is a feasible, safe, and reasonable treatment for elderly esophageal cancer patients. Achieving a better compliance to CRT via an optimal dose modification of chemotherapy may provide better clinical outcomes and would be the treatment goal for elderly esophageal cancer patients.
Early echocardiographic signs of diastolic dysfunction predict acute kidney injury in cirrhotic patients
Authors: Wu Pei-Shan , Wang Ying-Wen , Tai Cheng-Chun , Hsieh Yun-Cheng , Lee Pei-Chang , Huang Chin-Chou , Huang Yi-Hsiang , Hou Ming-Chih , Lin Han-Chieh , Lee Kuei-Chuan
Published: September 2020

Background:

Cardiovascular dysfunction in cirrhotic patients affects survival and the development of cirrhotic complications. We aimed to evaluate potential echocardiographic parameters to predict mortality and acute kidney injury (AKI) in cirrhotic patients.

Methods:

A total of 103 cirrhotic patients who underwent echocardiography between February 2009 and August 2016 in Taipei Veterans General Hospital were retrospectively enrolled. Cardiac function was evaluated using transthoracic two-dimensional echocardiography with tissue Doppler imaging. Cox hazard regression analysis was used for assessing predictors for 1-year mortality and AKI within 1 year.

Results:

Baseline echocardiographic parameters were similar between survivors (n = 92) and nonsurvivors (n = 11). Lower serum levels of albumin, as well as higher albumin-bilirubin (ALBI) scores, Child-Pugh scores, and model for end-stage liver disease scores were observed in nonsurvivors. Cox proportional hazard regression analysis revealed Child-Pugh score as the only predictor of 1-year mortality. Baseline serum creatinine (Cr) > 1.5 mg/dL, total bilirubin > 2 mg/dL, and a higher E/e′ ratio predict occurrence of AKI within 1 year. Among patients with serum Cr < 1.5 mg/dL, an increased atrial filling velocity and higher ALBI scores predict AKI occurrence within 1 year.

Conclusion:

Severity of underlying liver disease but not echocardiographic parameters predicts 1-year mortality in cirrhosis. Early echocardiographic signs of diastolic dysfunction and higher ALBI scores may predict development of AKI in cirrhotic patients with serum Cr < 1.5 mg/dL.