bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intradural Schwannoma Exacerbating the Symptoms of Degenerative Lumbar Stenosis: Case Report
Authors: Meguins Lucas , Abílio Raphael , Santos Herbert , Valsechi Linoel , Duarte Elísio , Morais Dionei 
Published: January 2017

Introduction Schwannoma is a common intradural slow-growing, benign and encapsulated tumor that originates from the myelin sheaths of the nerve fibers. However, a lumbar schwannoma complicating the symptoms of spinal stenosis is an extremely rare association.
Aim To describe the case of a woman presenting a lumbar schwannoma in association with spinal stenosis.
Case Report A 53 year-old female was referred to neurosurgical evaluation due to the worsening of a lumbar pain that was irradiating to the left inferior leg along the anterolateral surface. A neurological examination revealed motor deficits for extension of the left leg and attenuation of the left patellar reflex. Magnetic resonance imaging (MRI) showed lumbar spinal stenosis due to flavum ligament hypertrophy and disc herniation in the L3L4 and L4L5 segments, and an expansive lesion with homogeneous contrast enhancement occupying the left neuroforamen of the L3L4 segment. The patient underwent surgical resection of the tumor and decompression of the stenotic segments with posterior screw instrumentation from L3 to L5. She presented an uneventful recovery and significant improvement of the lumbar pain, and was still free of symptoms 6 months after surgery. An anatomopathological examination defined the tumor as a schwannoma (Grade I – World Health Organization [WHO]).
Conclusion The present study highlights that lumbar schwannoma is a possible etiology complicating the symptoms of patients with previous lumbar spinal stenosis. It is important to treat both pathologies to improve the patients' symptoms.
Family Medicine Physicians With Substance Use Disorder: A 5-year Outcome Study
Authors: Rose John S. , Campbell Michael D. , Yellowlees Peter , Skipper Gregory E. , DuPont Robert L. 
Published: January 2017

Objectives:
There is little published evidence on how well family medicine physicians (FMPs) with substance use disorder (SUD) perform in Physician Health Programs (PHPs). We examined outcomes for FMP compared with non-FMP physicians.

Methods:
This study utilized data from a 5-year, longitudinal, cohort study involving 904 physicians with diagnoses of SUD consecutively admitted to one of 16 state PHPs between 1995 and 2001. We compared 175 FMPs to 687 other physicians. Outcome measures were relapse, successful completion of monitoring contract at 5 years, and licensed and employed at 5 years.

Results:
Of the 3 outcome variables measured: relapse, successful completion of monitoring contract at 5 years, and licensed and employed at 5 years, FMPs had similar rates of success on all variables except monitoring contract completion at 5 years when compared with the other physician cohort.

Conclusions:
In this study, FMPs with SUD do as well as other physicians in PHPs at 5 years. However, FMPs were less likely to complete the monitoring contract at 5 years as compared to the other physician cohort.
Incorporating the patient's perspective in outcomes research
Authors: Hsiao Betty , Fraenkel Liana 
Published: January 2017

Purpose of review
Incorporation of the patients’ perspective in clinical research is critical to ensure that outcomes measured reflect those, which matter most to patients. This review summarizes recent efforts to include the patients’ perspective in the development of outcome measures and the importance of encouraging patient participation in decision-making and self-management.

Recent findings
Since the inclusion of fatigue as a patient-endorsed core outcome measure in rheumatoid arthritis (RA) trials, OMERACT has been instrumental in advocating for patient involvement in the development of core domains and instruments; current endeavors include cultivating an understanding of remission through the eyes of patients and gaining a sense of how to measure features of pain and ‘stiffness’ deemed as important to patients. The concept of remission was further explored in RA patients, highlighting a common goal of returning to normality; additionally, various tools have been developed to assess for unmet needs in rheumatology patients. Advances have also been made in the development and revision of patient-centered core measures in rheumatologic diagnoses outside of RA.

Summary
Incorporating the patients’ perspective is now considered an essential feature in outcomes research. Future research should focus on how best to involve patients in specific research activities.
Widespread Down-Regulation of Cardiac Mitochondrial and Sarcomeric Genes in Patients With Sepsis*
Authors: Matkovich Scot J. , Al Khiami Belal , Efimov Igor R. , Evans Sarah , Vader Justin , Jain Ashwin , Brownstein Bernard H. , Hotchkiss Richard S. , Mann Douglas L. 
Published: January 2017

Objectives:
The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts.

Design:
Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts.

Setting:
ICUs at Barnes-Jewish Hospital, St. Louis, MO.

Patients:
Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors.

Interventions:
None other than those performed as part of patient care.

Measurements and Main Results:
Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± sd). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA levels in septic cardiomyopathy were both distinct from and more profound than changes in messenger RNA levels in the hearts of patients with end-stage heart failure.

Conclusions:
The expression profile of messenger RNAs in the heart of septic patients reveals striking decreases in expression levels of messenger RNAs that encode proteins involved in cardiac energy production and cardiac contractility and is distinct from that observed in patients with heart failure. Although speculative, the global nature of the decreases in messenger RNA expression for genes involved in cardiac energy production and contractility suggests that these changes may represent a short-term adaptive response of the heart in response to acute change in cardiovascular homeostasis.
Early Goal-Directed Therapy for Sepsis: A Novel Solution for Discordant Survival Outcomes in Clinical Trials
Authors: Kalil Andre C. , Johnson Daniel W. , Lisco Steven J. , Sun Junfeng 
Published: January 2017

Objectives:
Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance.

Design:
Random-effects and Bayesian hierarchical analyses.

Setting:
Studies that evaluated early goal-directed therapy.

Subjects:
Patients with severe sepsis and/or septic shock.

Interventions:
Early goal-directed therapy.

Measurements and Main Results:
A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71–0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67–0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78–1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68–0.95); p = 0.01. Differences in age, country, hospital location, era, systolic pressure, mean arterial pressure, lactate, bundle compliance, amount of fluid administered, and hemodynamic goal achievements were not associated with survival differences between studies. Factors associated with mortality differences between early goal-directed therapy and control included Acute Physiology and Chronic Health Evaluation II (relative risk = 1.05 [1.02–1.09]; p = 0.003), Sequential Organ Failure Assessment (relative risk = 1.09 [1.00–1.18]; p = 0.04), presence of shock (relative risk = 1.007 [1.002–1.013]; p = 0.006), time-to-first antibiotic (relative risk = 1.22 [1.09–1.36]; p = 0.0006), antibiotic administration within 6 hours (relative risk = 0.20 [0.09–0.45]; p = 0.0001), 4 hours (relative risk = 0.16 [0.06–0.39]; p = 0.0001), and 3 hours (relative risk = 0.09 [0.03–0.27]; p < 0.0001). The only factors that explained mortality differences between randomized and observational studies were time-to-first antibiotic (R
2 = 87%), antibiotic administration within 6 hours (R
2 = 94%), 4 hours (R
2 = 99%), 3 hours (R
2 = 99%), and appropriate antibiotic use (R
2 = 96%).

Conclusions:
Survival discordance was not associated with differences in early goal-directed therapy bundle compliance or hemodynamic goal achievement. Our results suggest that it was associated with faster and more appropriate antibiotic co-intervention in the early goal-directed therapy arm compared with controls in the observational studies but not in the randomized trials. Early goal-directed therapy was associated with increased mortality in patients with high-disease severity.
Evolution of Fibroblastic Connective Tissue Nevus in an Infant
Authors: Lynch Michael C. , Samson Thomas D. , Zaenglein Andrea L. , Chung Catherine G. 
Published: January 2017

Abstract:
Fibroblastic connective tissue nevus (FCTN) is a rare and recently described neoplasm of fibroblastic/myofibroblastic lineage. We report a case of a 1-month-old healthy male infant who presented with a dermal plaque on the upper chest since birth. A punch biopsy demonstrated a dermal spindle-cell neoplasm with variable smooth muscle actin positivity and negative staining for CD34, consistent with myofibroma. Over the course of the next year, the remaining lesional tissue exhibited clinical softening and a surgical excisional specimen revealed histologic findings distinct from the original biopsy. These included a poorly circumscribed proliferation of bland spindle cells arranged in short fascicles centered in the dermis and extending into the subcutis with positivity for CD34, and absence of staining with smooth muscle actin features diagnostic of FCTN. Our case allowed the opportunity to see this unusual neoplasm at different stages, and we hypothesize that FCTN may undergo an early cellular phase and that time is required for these lesions to “mature” and demonstrate the more characteristic features of FCTN.
ACUTE CENTRAL SEROUS CHORIORETINOPATHY
Authors: Daruich Alejandra , Matet Alexandre , Marchionno Laetitia , De Azevedo Jean-Dominique , Ambresin Aude , Mantel Irmela , Behar-Cohen Francine 
Published: January 2017

Purpose:
To evaluate the influence of clinical and multimodal imaging parameters on the duration of acute central serous chorioretinopathy (CSCR) episodes.

Methods:
Consecutive patients with first, treatment-naïve central serous chorioretinopathy episodes presenting within 20 days of symptoms onset were prospectively included. They were reevaluated 15 days to 20 days later, followed by monthly evaluation for 6 months. Subfoveal choroidal thickness (SFCT), fluorescein leakage intensity on fluorescein angiography, elevation of retinal pigment epithelium (RPE) lesions at leakage sites, focal/multifocal pattern of indocyanine green angiography (ICGA) at baseline, time-dependent pattern of subretinal fluid (SRF) resorption on OCT using volume segmentation, history of corticosteroid intake and mean blood pressure were evaluated using univariate (Log rank test) and multivariate (Cox proportional hazard regression) survival analysis.

Results:
Thirty-one patients were included (26 men, 5 women, mean age: 40.0 ± 8.9 years, range: 24–58), of which 26 (84%) had episode resolution by 6 months. Using univariate analysis, episode duration was longer in cases with subfoveal choroidal thickness ≥500 μm (P = 0.0002), retinal pigment epithelium elevation at leakage sites ≥50 μm (P = 0.033), and a peak in subretinal fluid observed during follow-up (P = 0.013), and there was a near-significant association of intense fluorescein leakage (P = 0.074) with longer episodes. Using multivariate analysis, subfoveal choroidal thickness ≥500 μm (P = 0.017), retinal pigment epithelium elevation at leakage sites ≥50 μm (P = 0.010) and patient age ≥40 years (P = 0.010) were significantly and independently associated to longer episodes. Indocyanine green angiography pattern, corticosteroid intake, and blood pressure did not influence episode duration.

Conclusion:
Older age, higher subfoveal choroidal thickness, and higher degree of retinal pigment epithelium alteration at leakage sites are independent factors of longer acute central serous chorioretinopathy episodes.
Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15–18 Months of Age in Mexico
Authors: Melo Flor Irene Rodriguez , Morales José Juan Renteria , De Los Santos Abiel Homero Mascareñas , Rivas Enrique , Vigne Claire , Noriega Fernando 
Published: January 2017

Background:
The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated.

Methods:
This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed.

Results:
Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study.

Conclusion:
Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.
Insulin Resistance and Markers of Inflammation in HIV-infected Ugandan Children in the CHAPAS-3 Trial
Authors: Dirajlal-Fargo Sahera , Musiime Victor , Cook Adrian , Mirembe Grace , Kenny Julia , Jiang Ying , Debanne Sara , Klein Nigel , McComsey Grace A. 
Published: January 2017

Background:
Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation.

Methods:
We compared baseline and changes in insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART)–naive Ugandan children from the Children with HIV in Africa-Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens trial randomized to zidovudine-, stavudine- or abacavir (ABC)–based regimen. Nonparametric methods were used to explore between-group and within-group differences, and multivariable analysis to assess associations of HOMA-IR.

Results:
One-hundred eighteen children were enrolled, and median age (interquartile range) was 2.8 years (1.7–4.3). Baseline median HOMA-IR (interquartile range) was 0.49 (0.38–1.07) and similar between the arms. At week 48, median relative changes in HOMA-IR were 14% (−29% to 97%) in the zidovudine arm, −1% (−30% to 69%) in the stavudine arm and 6% (−34% to 124%) in the ABC arm (P ≤ 0.03 for all the arms compared with baseline, but P = 0.90 for between-group differences). Several inflammation markers significantly decreased in all study arms; soluble CD14 increased on ABC and did not change in the other 2 arms. In multivariate analysis, only changes in soluble CD163 were positively associated with HOMA-IR changes.

Conclusions:
In ART-naive Ugandan children, HOMA-IR changed significantly after 48 weeks of ART and correlated with monocyte activation.
Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial
Authors: Nielsen Rikke Vibeke , Fomsgaard Jonna Storm , Siegel Hanna , Martusevicius Robertas , Nikolajsen Lone , Dahl Jørgen Berg , Mathiesen Ole 
Published: January 2017

Abstract
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg−1·h−1 or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval −59 to −25), P < 0.001. Sedation was significantly reduced in the ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.
Epigenetic upregulation of CXCL12 expression mediates antitubulin chemotherapeutics–induced neuropathic pain
Authors: Xu Ting , Zhang Xiao-Long , Ou-Yang Han-Dong , Li Zhen-Yu , Liu Cui-Cui , Huang Zhen-Zhen , Xu Jing , Wei Jia-You , Nie Bi-Lin , Ma Chao , Wu Shao-Ling , Xin Wen-Jun 
Published: January 2017

Abstract
Clinically, Microtubule-targeted agents–induced neuropathic pain hampers chemotherapeutics for patients with cancer. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12 and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 using the transgenic mice (CXCL12−/+
) or neutralizing antibody or siRNA ameliorated the mEPSC's enhancement and mechanical allodynia. In addition, paclitaxel and vincristine both could increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the acetylation of histone H4 in the CXCL12-expressing neurons. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that antitubulin chemotherapeutics increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, and contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in CXCL12 gene promoter. Inhibition of STAT3 by intrathecal injection of adeno-associated virus encoding Cre and green fluorescent protein into STAT3flox/flox
mice or inhibitor S3I-201 into rats suppressed the CXCL12 upsurge by decreasing the acetylation of histone H4. Finally, blockade of CXCR4 but not CXCR7 ameliorated the paclitaxel- or vincristine-induced mechanical allodynia. Together, these results suggested that enhanced interaction between STAT3 and p300 mediated the epigenetic upregulation of CXCL12 in dorsal horn neurons, which contributed to the antitubulin chemotherapeutics–induced persistent pain.
Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia
Authors: Kubo Asako , Shinoda Masamichi , Katagiri Ayano , Takeda Mamoru , Suzuki Tatsuro , Asaka Junichi , Yeomans David C. , Iwata Koichi 
Published: January 2017

AbstractOxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor–immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K+channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K+current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K+channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.