bluuebunny/crossref_metadata_2025 huggingface dataset:
T2/FLAIR-mismatch sign for noninvasive detection of IDH-mutant 1p/19q non-codeleted gliomas: validity and pathophysiology
Authors: Foltyn Martha , Nieto Taborda Karen Natalia , Neuberger Ulf , Brugnara Gianluca , Reinhardt Annekathrin , Stichel Damian , Heiland Sabine , Herold-Mende Christel , Unterberg Andreas , Debus Jürgen , Deimling Andreas von , Wick Wolfgang , Bendszus Martin , Kickingereder Philipp
Published: January 2020

Background

This study aimed to assess the validity and pathophysiology of the T2/FLAIR-mismatch sign for noninvasive identification of isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted glioma.

Methods

Magnetic resonance imaging scans from 408 consecutive patients with newly diagnosed glioma (113 lower-grade gliomas and 295 glioblastomas) were evaluated for the presence of T2/FLAIR-mismatch sign by 2 independent reviewers. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the performance of the T2/FLAIR-mismatch sign for identifying IDH-mutant 1p/19q non-codeleted tumors. An exploratory analysis of differences in contrast-enhancing tumor volumes, apparent diffusion coefficient (ADC) values, and relative cerebral blood volume (rCBV) values in IDH-mutant gliomas with versus without the presence of a T2/FLAIR-mismatch sign (as well as analysis of spatial differences within tumors with the presence of a T2/FLAIR-mismatch sign) was performed.

Results

The T2/FLAIR-mismatch sign was present in 12 cases with lower-grade glioma (10.6%), all of them being IDH-mutant 1p/19q non-codeleted tumors (sensitivity = 10.9%, specificity = 100%, PPV = 100%, NPV = 3.0%, accuracy = 13.3%). There was a substantial interrater agreement to identify the T2/FLAIR-mismatch sign (Cohen’s kappa = 0.75 [95% CI, 0.57–0.93]). The T2/FLAIR-mismatch sign was not identified in any other molecular subgroup, including IDH-mutant glioblastoma cases (n = 5). IDH-mutant gliomas with a T2/FLAIR-mismatch sign showed significantly higher ADC (P < .0001) and lower rCBV values (P = .0123) as compared to IDH-mutant gliomas without a T2/FLAIR-mismatch sign. Moreover, in IDH-mutant gliomas with T2/FLAIR-mismatch sign the ADC values were significantly lower in the FLAIR-hyperintense rim as compared to the FLAIR-hypointense core of the tumor (P = .0005).

Conclusions

This study confirms the high specificity of the T2/FLAIR-mismatch sign for noninvasive identification of IDH-mutant 1p/19q non-codeleted gliomas; however, sensitivity is low and applicability is limited to lower-grade gliomas. Whether the higher ADC and lower rCBV values in IDH-mutant gliomas with a T2/FLAIR-mismatch sign (as compared to those without) translate into a measurable prognostic effect requires investigation in future studies. Moreover, spatial differences in ADC values between the core and rim of tumors with a T2/FLAIR-mismatch sign potentially reflect specific distinctions in tumor cellularity and microenvironment.
Comparison of Upper Extremity Function in Women With and Women Without a History of Breast Cancer
Authors: Fisher Mary Insana , Capilouto Gilson , Malone Terry , Bush Heather , Uhl Timothy L
Published: January 2020

Background

Breast cancer treatments often result in upper extremity functional limitations in both the short and long term. Current evidence makes comparisons against a baseline or contralateral limb, but does not consider changes in function associated with aging.

Objective

The objective of this study was to compare upper extremity function between women treated for breast cancer more than 12 months in the past and women without cancer.

Design

This was an observational cross-sectional study.

Methods

Women who were diagnosed with breast cancer and had a mean post–surgical treatment time of 51 months (range = 12–336 months) were compared with women who did not have breast cancer (CTRL group). Self-reported upper extremity function using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and shoulder range of motion, strength, and muscular endurance were measured. Participants were divided into 3 groups: breast cancer involving the nondominant limb (BC-ND), breast cancer involving the dominant limb (BC-DOM), and CTRL.

Results

A total of 59 women in the CTRL group, 23 women in the BC-ND group, and 28 women in the BC-DOM group completed measures. Mean DASH scores in women with breast cancer were higher than those of women in the CTRL group, regardless of the limb on which cancer occurred (Cohen d = 1.13; 95% CI = 2.20 to 16.21) Range of motion for the BC-ND group was significantly less for flexion (Cohen d = 1.19, 95% CI = −13.08 to −0.11) and external rotation (Cohen d = 1.11, 95% CI = −18.62 to −1.98) compared with the CTRL group. Strength in the BC-ND group was 23% to 25% lower in the CTRL group for external (Cohen’s d = 0.89, 95% CI = 0.09 to 0.12) and internal rotation (Cohen d = 0.92, 95% CI = 0.10 to 0.13). Endurance was not significantly different in the 3 groups.

Limitations

Some participants had rehabilitation, which may have skewed results. The range of post–surgical treatment times was broad, making it difficult to determine when function returned. Muscular endurance measures demonstrated a ceiling effect and large variance, limiting the ability to distinguish differences among participants. These results may not be generalizable to the subset of women who were treated with lumpectomy, sentinel node biopsy, or chest wall radiation alone or who underwent a contralateral prophylactic mastectomy.

Conclusion

In the long term, women with breast cancer have lower self-reported shoulder function than women without breast cancer. Motion and strength are lower among women who have experienced cancer on the nondominant limb.
Industry Structure and the Strategic Provision of Trade Credit by Upstream Firms
Authors: Lehar Alfred , Song Victor Y , Yuan Lasheng
Published: January 2020

Trade credit can serve as a collusion mechanism for competing supply chains to increase producer surplus in medium concentrated industries. We analyze theoretically how this form of financing influences retailers’ behavior in the product market, study incentives to deviate, and show evidence consistent with the model’s predictions. Trade credit use is inversely U shaped in industry concentration, and this pattern is more pronounced in industries more prone to collusion and when incentives to deviate are smaller.
Transfer ofXanthomonas campestrispv.arecaeandX. campestrispv.musacearumtoX. vasicola(Vauterin) asX. vasicolapv.arecaecomb. nov. andX. vasicolapv.musacearumcomb. nov. and Description ofX. vasicolapv.vasculorumpv. nov.
Authors: Studholme David J. , Wicker Emmanuel , Abrare Sadik Muzemil , Aspin Andrew , Bogdanove Adam , Broders Kirk , Dubrow Zoe , Grant Murray , Jones Jeffrey B. , Karamura Georgina , Lang Jillian , Leach Jan , Mahuku George , Nakato Gloria Valentine , Coutinho Teresa , Smith Julian , Bull Carolee T.
Published: January 2020

We present an amended description of the bacterial species Xanthomonas vasicola to include the causative agent of banana Xanthomonas wilt, as well as strains that cause disease on Areca palm, Tripsacum grass, sugarcane, and maize. Genome-sequence data reveal that these strains all share more than 98% average nucleotide with each other and with the type strain. Our analyses and proposals should help to resolve the taxonomic confusion that surrounds some of these pathogens and help to prevent future use of invalid names.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
How complementary feeding in infants affects allergies, chronic disease, and neurodevelopment
Authors: Duffy Diane M.
Published: January 2020

Recommendations for the timing and type of complementary foods to introduce to infants have recently changed. These changes are due to increased understanding of how these foods affect the development of food allergies, risk for obesity and other chronic diseases, and infant neurodevelopment. This article brings the current recommendations and recent research together and organizes them for clinicians in pediatrics to enable them to understand and convey this information to parents of infants.
Ropivacaine and Ketorolac Wound Infusion for Post–Cesarean Delivery Analgesia
Authors: Barney Emily Z. , Pedro Christina D. , Gamez Brock H. , Fuller Matthew E. , Dominguez Jennifer E. , Habib Ashraf S.
Published: January 2020

OBJECTIVE:

To evaluate the efficacy of wound infusion with ropivacaine plus ketorolac compared with placebo for post–cesarean delivery analgesia in women who received a multimodal analgesic regimen including intrathecal morphine.

METHODS:

In a randomized double-blind study, women undergoing scheduled cesarean delivery under spinal or combined spinal epidural anesthesia were randomized to wound infusion with ropivacaine 0.2% plus ketorolac, or saline placebo using an elastometric pump for 48 hours. The primary outcome was pain score with movement at 24 hours after surgery (0–10 scale, 0=no pain and 10=worst possible pain). Secondary outcomes included pain scores at rest at 24 hours, pain scores at rest and with movement at 2 and 48 hours, opioid consumption, and time to first rescue analgesic. A sample size of 35 per group (n=70) was planned.

RESULTS:

From November 8, 2016, to May 17, 2019, 247 women were screened, and 71 completed the study per protocol: 38 in the placebo group and 33 in the ropivacaine plus ketorolac group. Patient demographics and intraoperative characteristics were comparable between the groups. There was no significant difference between the groups in the primary outcome of pain score with movement at 24 hours (difference in median score 0, 95% CI −1 to 2, P=.94). There were also no significant differences between the placebo and ropivacaine plus ketorolac groups in pain scores at other time points, in total opioid consumption (difference in median consumption −12.5 mg, 95% CI −30 to 5, P=.11), or in time to rescue analgesics (median [interquartile range] 660 [9–1,496] vs 954 [244–1,710] minutes, hazard ratio 0.69, 95% CI 0.41 to 1.17, P=.16).

CONCLUSION:

There was no benefit of wound infusion with ropivacaine and ketorolac in women who received intrathecal morphine and a multimodal analgesic regimen.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02829944.

FUNDING SOURCE:

The study was supported in part by Avanos Medical Inc.
Perineorrhaphy Compared With Pelvic Floor Muscle Therapy in Women With Late Consequences of a Poorly Healed Second-Degree Perineal Tear
Authors: Bergman Ida , Westergren Söderberg Marie , Ek Marion
Published: January 2020

OBJECTIVE:

To evaluate outcomes after pelvic floor muscle therapy, as compared with perineorrhaphy and distal posterior colporrhaphy, in the treatment of women with a poorly healed second-degree obstetric injury diagnosed at least 6 months postpartum.

METHODS:

We performed a single center, open-label, randomized controlled trial. After informed consent, patients with a poorly healed second-degree perineal tear at minimum 6 months postpartum were randomized to either surgery or physical therapy. The primary outcome was treatment success, as defined by Patient Global Impression of Improvement, at 6 months. Secondary outcomes included the Pelvic Floor Distress Inventory, the Pelvic Floor Impact Questionnaire, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, and the Hospital Anxiety and Depression Scale. Assuming a 60% treatment success in the surgery group and 20% in the physical therapy group, plus anticipating a 20% loss to follow-up, a total of 70 patients needed to be recruited.

RESULTS:

From October 2015 to June 2018, 70 of 109 eligible patients were randomized, half into surgery and half into tutored pelvic floor muscle therapy. The median age of the study group was 35 years, and the median duration postpartum at enrollment in the study was 10 months. There were three dropouts in the surgery group postrandomization. In an intention-to-treat analysis, with worst case imputation of missing outcomes, subjective global improvement was reported by 25 of 35 patients (71%) in the surgery group compared with 4 of 35 patients (11%) in the physical therapy group (treatment effect in percentage points 60% [95% CI 42–78%], odds ratio 19 [95% CI 5–69]). The surgery group was superior to physical therapy regarding all secondary endpoints.

CONCLUSION:

Surgical treatment is effective and superior to pelvic floor muscle training in relieving symptoms related to a poorly healed second-degree perineal tear in women presenting at least 6 months postpartum.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02545218.
Topical Hemostatic Agents in Gynecologic Surgery for Benign Indications
Authors: Stachowicz Anne M. , Whiteside James L.
Published: January 2020

Since a variety of procoagulant products, collectively called hemostatic agents, became available to surgeons in the mid-20th century, their use has increased across multiple specialties, including gynecology. Congruent with past research on the causes of regional variation in the practice of medicine, available evidence suggests that a central predictor for use of these products is physician preference rather than documented clinical necessity. Use of these products adds risks and avoidable cost. This article seeks to highlight specific gynecologic circumstances in which evidence and surgical judgment supports hemostatic agent use and other settings in which use should be reconsidered.
SUMOylation of vascular endothelial growth factor receptor 2 inhibits the proliferation, migration, and angiogenesis signaling pathway in non-small cell lung cancer
Authors: Wang Mei , Jiang Xiaodong
Published: January 2020

Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in non-small cell lung cancer (NSCLC), and is the main target of antiangiogenesis therapy against this disease. However, there is limited evidence regarding its regulatory mechanism. Thus, elucidating the underlying mechanism of regulation of VEGFR2 is of great value to antiangiogenesis therapy. The colocalization of VEGFR2 and small ubiquitin-like modifier 1 (SUMO1) was detected through confocal microscopy. We examined the level of VEGFR2 SUMOylation in cells and rat tissues, and its effects on the angiogenesis signaling pathway (immunoprecipitation and western blotting), as well as the proliferation (Cell Counting Kit-8 assay) and migratory ability (cell scratch and Transwell assays) of NSCLC cells. Apoptosis was evaluated through Hoechst staining. VEGFR2 and SUMO1 are colocalized in the cytoplasm. VEGFR2 can be SUMOylated through combination with SUMO1 in cells and rat tissues, and the level of VEGFR2 SUMOylation in NSCLC is higher than that observed in healthy cells and tissues. Cell proliferation, migration, and the protein levels of phosphorylated-VEGFR2/phosphorylated-Akt/phosphorylated-extracellular signal-regulated kinase 1/2 (p-VEGFR2/p-Akt/p-ERK1/2) were significantly increased in NSCLC cells transfected with VEGFR2 K1270R versus those reported in cells transfected with VEGFR2 (wild-type). The levels of p-VEGFR2/p-Akt/p-ERK1/2 protein were significantly decreased in cells transfected with sentrin-specific protease 1-targeting small interfering RNA (siSENP1) versus those recorded in nontransfected controls. VEGFR2 SUMOylation may play an important role in antiangiogenesis therapy of NSCLC. The level of VEGFR2 SUMOylation may be a prognostic marker in patients with NSCLC.
Critical Care Bed Capacity in Asian Countries and Regions
Authors: Phua Jason , Faruq Mohammad Omar , Kulkarni Atul P. , Redjeki Ike Sri , Detleuxay Khamsay , Mendsaikhan Naranpurev , Sann Kyi Kyi , Shrestha Babu Raja , Hashmi Madiha , Palo Jose Emmanuel M. , Haniffa Rashan , Wang Chunting , Hashemian Seyed Mohammad Reza , Konkayev Aidos , Mat Nor Mohd Basri , Patjanasoontorn Boonsong , Nafees Khalid Mahmood Khan , Ling Lowell , Nishimura Masaji , Al Bahrani Maher Jaffer , Arabi Yaseen M. , Lim Chae-Man , Fang Wen-Feng ,   for the Asian Analysis of Bed Capacity in Critical Care (ABC) Study Investigators, and the Asian Critical Care Clinical Trials Group
Published: January 2020

Objective:

To assess the number of adult critical care beds in Asian countries and regions in relation to population size.

Design:

Cross-sectional observational study.

Setting:

Twenty-three Asian countries and regions, covering 92.1% of the continent’s population.

Participants:

Ten low-income and lower-middle–income economies, five upper-middle–income economies, and eight high-income economies according to the World Bank classification.

Interventions:

Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data.

Measurements and Main Results:

Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle–income economies (2.3; interquartile range, 1.4–2.7) than in upper-middle–income economies (4.6; interquartile range, 3.5–15.9) and high-income economies (12.3; interquartile range, 8.1–20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r
2 = 0.19; p = 0.047), the universal health coverage service coverage index (r
2 = 0.35; p = 0.003), and the Human Development Index (r
2 = 0.40; p = 0.001) on univariable analysis.

Conclusions:

Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle–income than in upper-middle–income and high-income countries and regions.
Association between variant alleles of major histocompatibility complex class II regulatory genes and nasopharyngeal carcinoma susceptibility
Authors: Zhou Ping , Liu Sha , Ji Nan-Nan , Zhang Shuang , Wang Peng , Lin Bing , Yang Ping , Lin Xian-Tao , Cai Yi-Zheng , Wang Zi-Ming , Zhou Han , Sun Shi-Yao , Hao Xin-Bao
Published: January 2020

Major histocompatibility complex (MHC) class II regulatory genes play a paramount role in immune response that can exert a predominant influence on clinical outcome of Epstein–Barr virus infection consistently assumed as the main pathogenetic factor for nasopharyngeal carcinoma. To elucidate the relationship between allelic variants ofMHCclass II regulatory genes and susceptibility to nasopharyngeal carcinoma, a total of 28 polymorphic loci atMHCclass II regulatory genes, involvingCIITA,CREB1,RFXfamily genes (RFX5,RFXAP,andRFXANK), andNFYfamily genes(NFYA,NFYB, andNFYC), were genotyped by multiplex SNaPshot minisequencing in 137 patients with nasopharyngeal carcinoma and 107 healthy controls from the southern Chinese population. Allelic analysis disclosed that rs7404873, rs6498121, rs6498126, and rs56074043 shared correlations with nasopharyngeal carcinoma (Ptrend< 0.05). Further, rs6498126 onCIITAwas independently associated with the risk of developing nasopharyngeal carcinoma (CC vs. GG, odds ratio: 7.386, 95% confidence interval: 1.934–28.207,Ptrend< 0.01). Conversely, rs7404873 onCIITAand rs56074043 onNFYBmanifested epistatic interaction to decreased susceptibility of nasopharyngeal carcinoma (rs7404873, TT vs. GG, odds ratio: 0.256, 95% confidence interval: 0.088–0.740,Ptrend< 0.05; rs56074043, AA vs. AG, odds ratio: 0.341, 95% confidence interval: 0.129–0.900,Ptrend< 0.05). Additionally, bioinformatics analysis revealed that the three variants were transcriptional regulatory in function and might impact the expression of nearby genes. The findings suggested genetic variants onMHCclass II regulatory genes contributed to nasopharyngeal carcinoma susceptibility and might provide new insights for screening high-risk population.
Transforming Nursing Education Through Interprofessional Collaborative Innovation
Authors: Haverkamp Jacqueline , Chovan John D. , Justice Stephanie , Ball Kay , Ballard Kacy C. , Batross Deana , Becker Jeffrey D. , Butz Sue , Chavez Ruth , Garrett Brian , Hummer Kirk , Johnson Vanessa , Prusinski Regina , Shoemaker Joy , Smith Amy L. , Zamaripa Christine
Published: January 2020

This project story is about transforming nursing education through interprofessional collaborative innovation to develop and use a complement of technology-based portable simulation devices collectively known as the Healthcare Education Simulation Station. This collection of inexpensive, simulated point-of-care instruments controlled wirelessly by an instructor or simulation operator were developed and field tested by an interdisciplinary team to enhance learning experiences in several configurations, including those using standardized patients and those using static and low-, mid-, and high-fidelity manikins. The core feature of this project story is the collaboration of students and faculty from two unrelated disciplines, nursing and engineering. The story includes a description of the development, field testing, and initial deployment of a simulated pulse oximeter, capnograph, automated sphygmomanometer, cardiac monitor, thermometer, and fetal monitor. Underpinning this project story is Rogers' Diffusion of Innovation theory and how the characteristics of the innovation, the personnel, and the environment worked together to enable this project and the innovation's subsequent diffusion into nursing education. The aspiration to improve learning experiences for students in multiple disciplines was paramount. The desire to acquire high-quality, dynamic educational tools for nursing educators, coupled with an environment that encourages collaboration, led to an innovation that can transform nursing preparation and ultimately improve patient care, while minimizing cost.
Single-port laparoscopy-assisted vaginal repair of a cesarean scar defect: a single-center retrospective study
Authors: Zhang Yong-Li , Wang Guo-Cheng , Qu Jun-Jie , Du Gui-Qiang , Zhou Wei-Qiang
Published: January 2020

Background:

The incidence of uterine cesarean scar defect (niche) is high, and some patients require surgery. Single-port laparoscopy can reduce post-operative pain, and provide better cosmetic effects. This study was performed to evaluate the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scar defect (niche) in women after cesarean section.

Methods:

This study included 74 patients who were diagnosed with uterine cesarean niche at the Shanghai First Maternity and Infant Hospital from January 2013 to June 2015. Thirty-seven patients underwent single-port laparoscopy-assisted vaginal surgery as the case group, and the remaining patients underwent vaginal repair surgery as the control group. We collected data from the inpatient and follow-up medical records. The clinical characteristics of these two groups were compared. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and multivariate analyses.

Results:

Patients who underwent single-port laparoscopy-assisted vaginal repair had a significantly longer operation time (2.3 [2.0–2.7] vs. 2.0 [1.6–2.3] h, P = 0.015), shorter gas passage time (1.2 [1.0–1.5] vs. 1.7 [1.0–2.0] days, P = 0.012), shorter hospital stay (3.1 [3.0–4.0] vs. 4.5 [4.0–6.0] days, P = 0.019), and fewer complications (0 vs. 4 cases). Univariate analysis showed that depth of the niche (P = 0.021) the mild adhesiolysis score (P = 0.035) and moderate adhesiolysis score (P = 0.013) were associated with the bladder injury. Multivariate analysis showed that the moderate adhesiolysis score (P = 0.029; 95% confidence interval, 1.318–3.526) was the strongest independent predictor of bladder injury.

Conclusion:

This study confirmed the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scars.
Comparison of the muscarinic antagonist effects of scopolamine and L-687,306
Authors: Winger Gail , Jutkiewicz Emily M. , Woods James H.
Published: January 2020

This study aimed to use central and peripheral assays to compare the effects of the muscarinic antagonist scopolamine with those of a novel muscarinic antagonist, L-687,306 [(3R,4R)-3-(3-cyclopropyl-1,2,4,oxadiazol[5-yl]-1-azabicyclo[2.2.1]heptane. Groups of rats were trained to discriminate the stimulus effects of the muscarinic agonist, arecoline (1.0 mg/kg); concomitant measures of response rate were recorded. Separate groups were prepared with telemetery devices for recording bradycardia induced by arecoline (10 mg/kg). Methyl arecoline and arecoline were nearly equally potent in producing a brief but profound bradycardia, indicative of an equivalent effect in the heart. L-687,306 and scopolamine were both able to block this peripheral effect of arecoline. L-687,306 produced a surmountable antagonism of both the discriminative and rate-suppressing effects of arecoline. Scopolamine, however, was unable to antagonize the rate-reducing effects of arecoline in the discrimination assay. This limited the number of rats that could respond to the discriminative stimulus effects of arecoline, as well as the amount of arecoline stimulus effects they were able to report. The data suggest that L-687,306 may be a more generally effective muscarinic antagonist than scopolamine and support earlier reports that this antagonist has less direct effect on behavior.
Cardiovascular Risk and Safety Evaluation of a Dual Peroxisome Proliferator–Activated Receptor-Alpha/Gamma Agonist, Aleglitazar, in Patients With Type 2 Diabetes: A Meta-analysis
Authors: Han Chun-Liu , Qu Chang-Zhi
Published: January 2020

This study evaluates the cardiovascular risk and safety of a dual peroxisome proliferator–activated receptor alpha and gamma (PPARα&γ), aleglitazar, for the management of type 2 diabetes mellitus. Studies were identified after a literature search in electronic databases and included in the meta-analysis according to eligibility criteria. Meta-analyses of mean differences in the changes from the baseline or odds ratios of selected indices between the aleglitazar- and the placebo/comparator-treated participants were performed. Seven studies {11,832 individuals; age 59.3 years [95% confidence interval (CI) 56.4–61.9]; body mass index 30.8 kg/m2 [95% CI 30.1–31.7]; sex, 54% males [44–64]} were included. In comparison with the placebo or pioglitazone, the aleglitazar treatment significantly improved %HbA1c, high-density lipoprotein-cholesterol (HDL-chol), and triglycerides. Aleglitazar also significantly decreased fasting plasma glucose and apolipoprotein B compared with the placebo. However, compared with the placebo or pioglitazone, aleglitazar significantly increased serum creatinine levels and significantly decreased the estimated glomerular filtration rate. In addition, the aleglitazar treatment was associated with a significantly increased body weight. Incidence of hypoglycemia, gastrointestinal hemorrhage, bone fractures, heart failure, cardiovascular death, and malignancy was higher in the aleglitazar group. Despite efficacy in glycemic and lipidic control, the aleglitazar treatment was associated with a poor safety profile.
The Volume-Outcome Paradigm for Gynecologic Surgery: Clinical and Policy Implications
Authors: WRIGHT JASON D.
Published: January 2020

Studies over the past decade have clearly demonstrated an association between high surgeon and hospital volume and improved outcomes for women undergoing gynecologic surgical procedures. In contrast to procedures associated with higher morbidity, the association between higher volume and improved outcomes is often modest for gynecologic surgeries. The lower magnitude of this association has limited actionable policy changes for gynecologic surgery. These data have been driving initiatives such as regionalization of care, targeted quality improvement at low volume centers and volume-based credentialing in gynecology.
VARIX OF A VORTEX VEIN AMPULLA INDUCED BY NODULAR SCLERITIS
Authors: Cabral Diogo , Nogueira Vanda
Published: January 2020

Purpose:

To describe a patient with a painful red-eye syndrome and a choroidal mass lesion that was diagnosed after multimodal imaging with a vortex vein ampulla varix induced by a nodular posterior scleritis.

Methods:

Retrospective case report documented with fluorescein angiography, indocyanine green angiography, b-mode ultrasound, fundus imaging, and swept-source optical coherence tomography.

Results:

A 24-year-old man presented with a painful red eye and sudden onset blurred vision. Fundus exam disclosed macular choroidal folds and a nonpigmented mass lesion at the inferior equator. Swept-source optical coherence tomography showed enlarged choroidal vessels with fluid in the suprachoroidal space under the central macula and a hyporeflective lobulated choroidal cavity in the inferior temporal retina. Multimodal imaging with contrast dyes showed a dilated vortex vein ampulla with early hyperfluorescence and a complete washout in late acquisitions on indocyanine green. The patient recovered uneventfully after a short-course administration of oral nonsteroidal anti-inflammatory drugs, disclosing irregular scleral nodules on swept-source optical coherence tomography that remained stable over a twelve-month follow-up.

Conclusion:

This report suggests that nodular posterior scleritis can induce a vortex vein ampulla varix and contributes to a better understanding of the pathophysiology of this entity. We further suggest that in a diagnostic puzzling scenario the inflammatory syndrome should be treated before attempting to perform a chorioretinal biopsy.
Toward a new definition of glaucomatous optic neuropathy for clinical research
Authors: Iyer Jayant , Vianna Jayme R. , Chauhan Balwantray C. , Quigley Harry A.
Published: January 2020

Purpose of review

A process is ongoing to produce a definition of glaucomatous optic neuropathy (GON) using quantitative, objective data from structural and functional tests. At present, a common practice is to define GON by subjective features said to be ‘characteristic’ as judged by those experienced in glaucoma care.

Recent findings

An objective definition would standardize the comparison of clinical research results across studies, without precluding simultaneous use of idiosyncratic definitions in the same reports. To achieve this goal, expert opinion was solicited to reach optimal agreement on one or more consensus, GON definitions. An interactive period of online discussion by 176 international experts led to 110 responses in an online survey that narrowed possible definitional structures into testable criteria.

Two approaches to validation of one or more sets of criteria for definite and possible GON are ongoing. The general principles include definition for each eye individually, inclusion of a borderline category, no intraocular pressure criterion, and both structural and functional defects in appropriate physical locations. Each validation approach uses clinician diagnosis as a standard against which objective criteria are compared, with the initial approach using a three-level categorical scale, and the second approach using 0--100 scaling.
Early Administration of Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the Risk of Influenza B Virus-Associated Pneumonia in Hospitalized Pediatric Patients with Influenza B Virus Infection
Authors: Dai Zhichu , Zhang Li , Yu Qinqing , Liu Lichang , Yang Meixiang , Fan Kitling
Published: January 2020

We conducted a retrospective study to identify the risk factors for pneumonia in hospitalized pediatric patients with influenza B infection. Receiving oseltamivir within the first 48 hours of onset and frequent cough was respectively considered as a protective factor and a risk factor for the influenza B virus-associated pneumonia in hospitalized pediatric patients. Early administration of oseltamivir can reduce the risk of influenza B virus-associated pneumonia.
Mechanistic pain profiling in young adolescents with patellofemoral pain before and after treatment: a prospective cohort study
Authors: Holden Sinéad , Rathleff Michael Skovdal , Thorborg Kristian , Holmich Per , Graven-Nielsen Thomas
Published: January 2020

Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pronociceptive and antinociceptive mechanisms in young adolescents with PFP, their impact on prognosis, and responsiveness to treatment. Adolescents (N = 151, aged 10-14 years) diagnosed with PFP were compared with age-matched controls (N = 50) and subsequently tracked while participating in an intervention focussed on activity modification. They underwent quantitative sensory testing at baseline (preintervention), 4 weeks (during initial treatment), and 12 weeks (after treatment). Pressure pain thresholds (PPTs) were recorded on the knee, shin, and elbow. Temporal summation of pain (TSP) was assessed by the increase in pain intensity during 10 repeated cuff pressure pain stimulations on the leg. Conditioned pain modulation (CPM) was defined as change in cuff pain thresholds on one leg, during painful cuff conditioning on the contralateral leg. At baseline, adolescents with PFP had decreased PPTs at the knee, shin, and elbow (P < 0.001) as well as more facilitated TSP (P < 0.05) compared with controls. For CPM at baseline, controls displayed an increase in cuff pain thresholds during conditioning (P < 0.05), while those with PFP did not. More facilitated baseline TSP was associated with less improvements in pain intensity during the intervention (P < 0.01). Pressure pain thresholds increased at both follow-ups (P < 0.001), and the increased PPTs were associated with decreases in pain intensity (r = 0.316; P < 0.001). Overall, TSP remained facilitated at follow-ups, and there was no change in CPM. This is the first study to demonstrate a pronociceptive mechanism as a prognostic factor in young adolescents with PFP.
An unbiased and efficient assessment of excitability of sensory neurons for analgesic drug discovery
Authors: Mohammed Zainab A. , Kaloyanova Katerina , Nassar Mohammed A.
Published: January 2020

Alleviating chronic pain is challenging, due to lack of drugs that effectively inhibit nociceptors without off-target effects on motor or central neurons. Dorsal root ganglia (DRG) contain nociceptive and non-nociceptive neurons. Drug screening on cultured DRG neurons, rather than cell lines, allows for the identification of drugs most potent on nociceptors with no effects on non-nociceptors (as a proxy for unwanted side effects on central nervous system and motor neurons). However, screening using DRG neurons is currently a low-throughput process, and there is a need for assays to speed this process for analgesic drug discovery. We previously showed that veratridine elicits distinct response profiles in sensory neurons. Here, we show evidence that a veratridine-based calcium assay allows for an unbiased and efficient assessment of a drug effect on nociceptors (targeted neurons) and non-nociceptors (nontargeted neurons). We confirmed the link between the oscillatory profile and nociceptors, and the slow-decay profile and non-nociceptors using 3 transgenic mouse lines of known pain phenotypes. We used the assay to show that blockers for Nav1.7 and Nav1.8 channels, which are validated targets for analgesics, affect non-nociceptors at concentrations needed to effectively inhibit nociceptors. However, a combination of low doses of both blockers had an additive effect on nociceptors without a significant effect on non-nociceptors, indicating that the assay can also be used to screen for combinations of existing or novel drugs for the greatest selective inhibition of nociceptors.
Interobserver agreement of the visual Herder scale for the assessment of solitary pulmonary nodules on 18F Fluorodeoxyglucose PET/computed tomography
Authors: Ordidge Katherine L. , Gandy Nemi , Arshad Mubarik A. , Wallitt Kathryn , Soneji Neil , Khan Sameer , Barwick Tara D.
Published: January 2020

Background

British Thoracic Society guidelines recommend 18F Fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) for solitary pulmonary nodule (SPN) follow-up in high-risk individuals or if the CT Brock score is >10%. Nodule tracer uptake is assessed visually in comparison to the surrounding lung tissue and mediastinal blood pool (Herder score). This score is used to calculate the risk of malignancy and guide patient management. Despite its widespread use, there have been no studies to date looking at interobserver agreement using the Herder scale.

Patients and methods

18F-FDG PET/CT studies of 100 consecutive patients imaged for the evaluation of SPN were retrospectively analysed. Anonymized images were reviewed independently by three Consultant Nuclear Medicine Radiologists and the Herder score was documented, along with a confidence score graded 1–3, where 1 indicated ‘not at all confident’ and 3 indicated ‘very confident’. Interobserver agreement was assessed using interclass correlation coefficient modelling.

Results

There was complete reviewer agreement in 81% cases, and interclass correlation with Cronbach’s alpha was excellent at 0.973 (95% confidence interval, 0.962–0.981). The agreement between pairs of reviewers was good and confidence scores using the Herder scale were high, with reviewers giving a confidence score of 3 in an average of 78% of cases.

Conclusion

Our study suggests excellent interobserver agreement for use of the Herder scale in evaluating SPNs. Reviewer confidence scores were high reflecting high confidence in the use of the Herder scale for evaluating SPN.
Tumor protein 53 mutations in acute myeloid leukemia: conventional induction chemotherapy or novel therapeutics
Authors: Asghari Hannah , Talati Chetasi
Published: January 2020

Purpose of review

Tumor protein 53 (TP53) protein is involved in fundamental processes of cancer, aging, and DNA repair. Thus, TP53 dysfunction is implicated in malignant processes and remains the most commonly mutated gene in cancer but represents a relatively small proportion in acute myeloid leukemia (AML). Patients with TP53-mutated AML attain inferior responses to therapy resulting in poor overall outcomes.

Recent findings

Traditional treatment approaches with conventional chemotherapy yields suboptimal responses for patients with TP53 mutant AML compared with wildtype TP53. In recent years, there is increasing interest in understanding the role and underlying biology of TP53 mutations in AML with efforts to harness the physiological tumor suppressive function of TP53 protein. Novel combination and targeted therapies may contribute to improved outcomes; however, responses to therapy may be short-lived and ongoing research is indicated to evaluate relapse-risk reduction strategies. These patients may benefit from consideration of enrollment in clinical trials or lower intensity therapy approaches in lieu of intensive chemotherapy.

Pharmacological treatments targeting the TP53 pathway in addition to novel emerging therapeutics and immunotherapy-based approaches hold promise for treatment of TP53 mutant AML.
Student Perceptions Related to Immediate Workplace Usefulness of RN-to-BSN Program Content
Authors: Sitzman Kathleen , Carpenter Tristin , Cherry Kim
Published: January 2020

BACKGROUND

Despite a national directive for associate degree in nursing (ADN) nurses to complete BSN degrees, there is limited research related to student perceptions of the value added by BSN education.

PURPOSE

The purpose was to explore perceptions of immediate workplace usefulness of RN-to-BSN content for ADNs.

METHODS

Qualitative narrative data provided by 263 RN-BSN students in their final semester before graduating with a BSN were analyzed. Students were asked, “How have you used what you are learning in the RN-BSN program at work?”

RESULTS

Themes included the following: research and evidence-based practice, leadership, professionalism, communication, intentional holistic caring, critical thinking, cultural competence, safety and quality improvement, interdisciplinarity, population-based care, and fiscal awareness.

CONCLUSION

Results clarified content that students found useful and provided insight into specific benefits that employers might expect to see when ADNs complete BSN-level education.
Sepsis in Complex Patients in the Emergency Department
Authors: Fesnak Sarah , Abbadessa Mary Kate , Hayes Katie , Ostapenko Svetlana , Lavelle Jane , Zorc Joseph J. , Balamuth Fran
Published: January 2020

Objectives

To compare timeliness of sepsis recognition and initial treatment in patients with and without high-risk comorbid conditions.

Methods

This was a retrospective cohort study of patients presenting to a pediatric emergency department (ED) who triggered a vital sign-based electronic sepsis alert resulting in bedside “huddle” assessment per institutional practice. A positive sepsis alert was defined as age-specific tachycardia or hypotension, concern for infection, and at least 1 of the following: abnormal capillary refill, abnormal mental status, or a high-risk condition. High-risk conditions were derived from the American Academy of Pediatrics sepsis alert tool. Patients with a positive alert underwent bedside huddle resulting in a decision regarding initiation of sepsis protocol. Placement on the protocol and time to initiation of protocol and individual therapies were compared for patients with and without high-risk conditions.

Results

During the 1-year study period, there were 1107 sepsis huddle alerts out of 96,427 ED visits. Of these, 713 (65%) had identified high-risk conditions, and 394 (35%) did not. Among patients with sepsis huddles, there was no difference in sepsis protocol initiation for patients with high-risk conditions compared with those without (24.8% vs 22.0%, P = 0.305). Between patients with high-risk conditions and those without, there were no differences in median time from triage to sepsis protocol activation, triage to initial intravenous antibiotic, triage to initial intravenous fluid therapy, or ED length of stay.

Conclusions

Timeliness of care initiation was no different in high-risk patients with sepsis when using an electronic sepsis alert and protocolized sepsis care.
An Update on Cryopreservation of Adipose Tissue
Authors: Gal Shaili , Pu Lee L. Q.
Published: January 2020

Currently, fat transplantation occurs immediately after harvesting procedures. Because low rates of fat graft take are well reported in the literature, many patients require multiple surgical procedures for fat graft harvest. These subsequent procedures lead to increased cost, donor-site morbidity, and patient discomfort in the long term. The ability to preserve our patients’ own adipose aspirate would allow us to counteract these shortcomings and ultimately improve the clinical outcome after fat grafting. Unfortunately, there is no optimal and practical adipose tissue cryopreservation protocol for use by the plastic surgeon at the present time. Because of this dilemma, the senior author (L.L.Q.P.) has investigated this concept in an effort to create a protocol that is both technically sound and clinically achievable to allow for the long-term preservation of adipose tissue. In this article, the authors aim to outline this effort, review current clinical applications that have been reported in the literature, and detail exciting future perspectives in the use of preserved lipoaspirates for repeated fat grafting procedures or in the form of cell-based therapy engineered for reconstructive endeavors for their patients.
Pain in Clients Attending a South African Voluntary Counseling and Testing Center Was Frequent and Extensive But Did Not Depend on HIV Status
Authors: Wadley Antonia L. , Lazarus Erica , Gray Glenda E. , Mitchell Duncan , Kamerman Peter R.
Published: January 2020

Background:

The frequency of pain is reported to be high in people living with HIV, but valid comparisons between people living with HIV and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV.

Setting:

Participants were recruited from an HIV voluntary counseling and testing center at the Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.

Methods:

Pain was assessed using the Wisconsin Brief Pain Questionnaire. Depressive and anxiety symptomatology was determined using the Hopkins Symptom checklist-25. We then stratified by HIV status.

Results:

Data from 535 black South Africans were analyzed: HIV-infected n = 70, HIV-uninfected n = 465. Overall, frequency of any current pain was high with 59% [95% confidence interval (CI): 55 to 63, n: 316/535] of participants reporting pain, with no difference related to HIV status: HIV-infected 50% (95% CI: 37 to 61, n: 35/70), HIV-uninfected 60% (95% CI: 56 to 65, n: 281/465). Pain intensity and number of pain sites were similar between the groups as were symptoms of anxiety and depression: mean Hopkins Symptom Checklist-25 1.72 (95% CI: 1.57 to 1.87) HIV-infected participants and 1.68 (95% CI: 1.63 to 1.73) HIV-uninfected participants. Univariate analysis showed female sex and greater depressive and anxiety symptomatology associated with pain. In a multivariable modeling, only depressive and anxiety symptomatology was retained in the model.

Conclusion:

The high frequency of pain found in both HIV-infected and HIV-uninfected individuals presenting at a voluntary counseling and testing center was more likely to be associated with depression and anxiety, than with the presence or absence of HIV.
Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting
Authors: Greenberg Lauren , Ryom Lene , Wandeler Gilles , Grabmeier-Pfistershammer Katharina , Öllinger Angela , Neesgaard Bastian , Stephan Christoph , Calmy Alexandra , Rauch Andri , Castagna Antonella , Spagnuolo Vincenzo , Johnson Margaret , Stingone Christof , Mussini Cristina , De Wit Stéphane , Necsoi Coca , Campins Antoni A. , Pradier Christian , Stecher Melanie , Wasmuth Jan-Christian , Monforte Antonella d'Arminio , Law Matthew , Puhr Rainer , Chkhartishvilli Nikoloz , Tsertsvadze Tengiz , Garges Harmony , Thorpe David , Lundgren Jens D. , Peters Lars , Bansi-Matharu Loveleen , Mocroft Amanda ,   RESPOND Study Group
Published: January 2020

Background:

Despite increased integrase strand transfer inhibitor (INSTI) use, limited large-scale, real-life data exists on INSTI uptake and discontinuation.

Setting:

International multicohort collaboration.

Methods:

RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan–Meier and Cox proportional hazards models describe time to and factors associated with discontinuation.

Results:

Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, and 2718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non–AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months.

Conclusions:

Uptake of DTG vs EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly because of treatment simplification.