bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis
Authors: Jin Xingzhong , Antony Benny , Wang Xia , Persson Monica SM , McAlindon Timothy , Arden Nigel K , Srivastava Sudeepti , Srivastava Rajeshwar , Van Middelkoop Marienke , Bierma-Zeinstra Sita MA , Zhang Weiya , Cicuttini Flavia , Ding Changhai
Published: April 2020

Introduction

Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function.

Methods and analysis

A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest.

Ethics and dissemination

Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations.

PROSPERO registration number

CRD42018107740.
Incidence, types and acceptability of pharmaceutical interventions about drug related problems in a general hospital: an open prospective cohort
Authors: Saldanha Valdjane , Randall Martins Rand , Lima Sara Iasmin Vieira Cunha , Batista de Araujo Ivonete , Gouveia Oliveira Antonio
Published: April 2020

Objectives

To evaluate the incidence and types of drug-related problems (DRP) in a general teaching hospital and to evaluate the acceptability of pharmaceutical interventions by the medical team.

Design

Prospective cohort study during 2 years.

Setting

Conducted in a Brazilian University Hospital.

Participants

The patient cohort consisted of 9303 patients with a total of 12 286 hospitalisation episodes.

Primary outcome measures

DRP detected by pharmacists’ review of 100% medication orders using Pharmaceutical Care Network Europe 6.2 classification.

Results

Patients with a mean age of 52.6±17.7 years and 50.9% females. A total of 3373 DRP in 1903 hospital episodes were identified, corresponding to a cumulative incidence of 15.5%. ‘Treatment ineffectiveness’ (11.5%) and ‘Treatment costs’ (5.90%) were the most common DRP and ‘Drug use process’ (18.4%) and ‘Treatment duration’ (31.0%) the main causes of DRP. The medicines involved most often involved in DRP were anti-infectives (36.0%), mainly cephalosporins (20.2%), antiulcer (38.6%), analgesics/antipyretics (61.2%), propulsives (51.2%), opioids (38.5%) and antiemetics (57.4%). From 1939 pharmaceutical interventions, at least, 21.4% were not approved by the medical team.

Conclusion

DRP detected by 100% medication order review by hospital pharmacists occur in a significant proportion of hospital episodes, the most frequent being related to treatment effectiveness and treatment costs. The medications mostly involved were cephalosporins, penicillins, antidyspeptics, analgesics, antipyretics, opioids and antiemetics. Pharmaceutical interventions had low acceptability by the medical staff.
Ethical aspects of time in intensive care decision making
Authors: Seidlein Anna-Henrikje , Hannich Arne , Nowak Andre , Gründling Matthias , Salloch Sabine
Published: April 2020

The decision-making environment in intensive care units (ICUs) is influenced by the transformation of intensive care medicine, the staffing situation and the increasing importance of patient autonomy. Normative implications of time in intensive care, which affect all three areas, have so far barely been considered. The study explores patterns of decision making concerning the continuation, withdrawal and withholding of therapies in intensive care. A triangulation of qualitative data collection methods was chosen. Data were collected through non-participant observation on a surgical ICU at an academic medical centre followed by semi-structured interviews with nurses and physicians. The transcribed interviews and observation notes were coded and analysed using qualitative content analysis according to Mayring. Three themes related to time emerged regarding the escalation or de-escalation of therapies: influence of time on prognosis, time as a scarce resource and timing in regards to decision making. The study also reveals the ambivalence of time as a norm for decision making. The challenge of dealing with time-related efforts in ICU care results from the tension between the need to wait to optimise patient care, which must be balanced against the significant time pressure which is characteristic of the ICU setting.
Suffering and the moral orientation of presence: lessons from Nazi medicine for the contemporary medical trainee
Authors: Frush Benjamin Wade , Malone Jay R
Published: April 2020

Medical trainees should learn from the actions of Nazi physicians to inform a more just contemporary practice by examining the subtle assumptions, or moral orientations, that led to such heinous actions. One important moral orientation that still informs contemporary medical practice is the moral orientation of elimination in response to suffering patients. We propose that the moral orientation of presence, described by theologian Stanley Hauerwas, provides a more fitting response to suffering patients, in spite of the significant barriers to enacting such a moral orientation for contemporary trainees.
Impact of workplace injury on opioid dependence, abuse, illicit use and overdose: a 36-month retrospective study of insurance claims
Authors: Asfaw Abay , Boden Leslie I
Published: April 2020

Objectives

To examine the impact of workplace injury on opioid dependence, abuse and overdose (opioid-related morbidity) and if severity of injury increases the hazard of these health effects.

Methods

We used MarketScan databases to follow injured and propensity score matched non-injured workers, both without prior opioid-related diagnoses. Using a Cox proportional hazard model, we examined the impact of workplace injury on opioid-related morbidity.

Results

The hazard of opioid-related morbidity for injured workers was 1.79 times than that of matched non-injured workers (95% CI 1.89 to 3.60). For medical-only and lost-time injured workers, it was respectively 1.54 (95% CI 1.02 to 2.32) and 2.91 (95% CI 1.75 to 4.84) times that of non-injured workers.

Conclusions

Reducing workplace injury or severity of workplace injury, as well as efforts to ensure appropriate opioid prescribing for injured workers, may help to reduce the societal costs of opioid use.
Genetic mechanisms underlying feed utilization and implementation of genomic selection for improved feed efficiency in dairy cattle
Authors: Brito Luiz F. , Oliveira Hinayah R. , Houlahan Kerry , Fonseca Pablo A.S. , Lam Stephanie , Butty Adrien M. , Seymour Dave J. , Vargas Giovana , Chud Tatiane C.S. , Silva Fabyano F. , Baes Christine F. , Cánovas Angela , Miglior Filippo , Schenkel Flavio S.
Published: April 2020

The economic importance of genetically improving feed efficiency has been recognized by cattle producers worldwide. It has the potential to considerably reduce costs, minimize environmental impact, optimize land and resource use efficiency, and improve the overall cattle industry’s profitability. Feed efficiency is a genetically complex trait that can be described as units of product output (e.g., milk yield) per unit of feed input. The main objective of this review paper is to present an overview of the main genetic and physiological mechanisms underlying feed utilization in ruminants and the process towards implementation of genomic selection for feed efficiency in dairy cattle. In summary, feed efficiency can be improved via numerous metabolic pathways and biological mechanisms through genetic selection. Various studies have indicated that feed efficiency is heritable, and genomic selection can be successfully implemented in dairy cattle with a large enough training population. In this context, some organizations have worked collaboratively to do research and develop training populations for successful implementation of joint international genomic evaluations. The integration of “-omics” technologies, further investments in high-throughput phenotyping, and identification of novel indicator traits will also be paramount in maximizing the rates of genetic progress for feed efficiency in dairy cattle worldwide.
Through-Plane Conductivity of Anion Exchange Membranes at Sub-Freezing Temperatures—Hydroxide vs (Bi-)Carbonate Ions
Authors: Schwämmlein Jan N. , Pham Nhat Long T. , Mittermeier Thomas , Egawa Masamitsu , Bonorand Lukas , Gasteiger Hubert A.
Published: April 2020

Anion exchange membrane fuel cells (AEMFCs) are considered as potential future alternative for proton exchange membrane fuel cells (PEMFCs) due to their potential to not require platinum. However, many properties of alkaline ionomers/membranes are not yet well-characterized. The goal of this study is to evaluate the suitability of current AEMs for application in a wide range of operating conditions, especially at temperatures below the freezing point of water. For this, a method was developed to reversibly convert the counter ion of the cationic group in the membrane electrode assembly (MEA) from (bi-)carbonate to hydroxide and vice versa. Subsequently, the through-plane membrane conductivity in an AEMFC was evaluated by electrochemical impedance spectroscopy at different temperatures (−20°C to 50°C) and water contents, whereby the electrical resistance contribution (contact and through-plane) to the high frequency resistance of the cell was determined in an ex-situ experiment. The results obtained in this study were compared to a standard PEM (Nafion 212) and to a sulfonic acid based membrane with a hydrocarbon backbone. The here acquired conductivity data suggest that the conductivity of the evaluated anion exchange membrane, particularly in its (bi-)carbonate form, would be too low at sub-zero temperature to meet automotive freeze start requirements.
Post-Test Raman Investigation of Silver Based Gas Diffusion Electrodes
Authors: Jovanovic Sven , Krause Ralf , Lüken Alexander , Ackermann Jörg , Merz Steffen , Jakes Peter , Eichel Rüdiger-A. , Granwehr Josef
Published: April 2020

Gas diffusion electrodes are used to overcome mass transport limitations of the electrochemical conversion of CO2. Long-time stability remains one of the key challenges for industrial application. A deactivation mechanism is the formation of carbon on the electrode surface, blocking the active sites of the catalyst. We investigated the effect of 100 h of electrochemical CO2 reduction at a current density of 100 mA cm−2 on a silver based gas diffusion electrode by means of Raman microscopy. Although there was no degradation in electrochemical performance, a darkening of the electrode surface was observed. Raman measurements of the darkened surface revealed intensive carbon signals. Both the darkened surface as well as the carbon signals persisted after washing. However, a surface darkening could also be observed for silver electrodes used for electrolysis in carbon free, aqueous media. This suggests that a formation of nanostructures on the electrode surface rather than the formation of a carbon layer is causing the surface darkening. Such structures enable Surface Enhanced Raman Scattering (SERS) and cause signal enhancement of environmental carbon on the electrode. The changes in surface structure were confirmed with scanning electron microscopy (SEM), and SERS experiments were carried out for verification of the enhancement effect.
Revisiting the t0.5 Dependence of SEI Growth
Authors: Attia Peter M. , Chueh William C. , Harris Stephen J.
Published: April 2020

SEI growth in lithium-ion batteries is commonly assumed to scale with t
0.5, in line with simple models of diffusion-limited surface layer growth. As a result, this model is widely used for empirical predictions of capacity fade in lithium-ion batteries. However, the t
0.5 model is generally not theoretically sufficient to describe all of the various SEI growth modes. Furthermore, previous literature has not convincingly demonstrated that this model provides the best fit to measurements of SEI growth. In this work, we discuss the theoretical assumptions of the t
0.5 model, evaluate claims of t
0.5 dependence in six previously published datasets and one new dataset, and compare the performance of this model to that of other models. We find that few of the purported t
0.5 fits in literature are statistically justified, although t
0.5 generally describes SEI growth during storage better than SEI growth during cycling. Finally, we evaluate how the fitted exponents in the power-law models vary as a function of time, and we illustrate the limitations of using t
0.5 for prediction without validating its applicability to a particular dataset. This work illustrates the theoretical and empirical limitations of the t
0.5 model and highlights alternatives for more accurate estimates and predictions of SEI growth.
Experimental and Theoretical Examination of Low-Current Overcharge at Lithiated-Graphite Porous Electrodes
Authors: Verbrugge Mark W. , Xiao Xingcheng , Baker Daniel R.
Published: April 2020

We determine if a recently developed model for describing the thermodynamics of lithiated graphite in equilibrium with plated Li (lithium) is consistent with well-controlled, low-current-density experiments that lead to Li plating on lithiated graphite. We show through numerical differentiation of the experimental data how to identify when Li plating is taking place. Plating (overcharge) occurs well before the electrode potential falls to 0 V vs Li, which is consistent with underpotential deposition of Li on graphite. This observation (i) cannot be reproduced by today’s porous electrode models that do not incorporate the underpotential deposition of Li on the graphite surface, and (ii) is consistent with the Li activity model recently developed.
Rolling in the Deep: Imaging Findings and Diagnostic Pearls in Gallstone Ileus
Authors: Aldo Carnevale , Lorenzo Motta , Olgerta Labaj , Alberto Cossu , Licia Uccelli , Melchiore Giganti
Published: April 2020

Gallstone ileus is a dramatic complication of gallstone disease, uncommon but not exceptional in a busy emergency department. It represents a cause of mechanical intestinal obstruction, which predominantly occurs in elderly and frail patients; this contributes to the high morbidity and mortality rates associated with this condition. The modern radiologist is frequently asked to determine the cause of bowel obstruction and should be aware of the most pictorial features of this unusual disease. Broadly speaking, abdominal radiography and ultrasonography alone are limited in detecting the cause of bowel obstruction, but the sensitivity for the preoperative diagnosis of gallstone ileus may be improved by combining the findings obtained by both techniques. Computed tomography is the modality of choice for the diagnosis of this disease: it may accurately describe the number, size, and location of migrated gallstones and the exact site of bowel obstruction, providing a detailed preoperative planning. Magnetic resonance imaging may be used in selected cases for an exquisite anatomic definition of the fistulous communication.
HPTLC Fingerprint Profile and Identification of Antidiabetic and Antioxidant Leads from Bauhinia rufescens L
Authors: Osman Wadah , Mohammed Mona S , Khalid Hassan S , Muddathir Abdelkhalig , Shantier Shaza W. , Osman Bashier , Abdoon Iman
Published: April 2020

Diabetes is one of the world’s major health problems, and many reports have supported the role of oxidative stress in the pathogenesis of both type 1 and type 2 diabetes. The present study aims to evaluate the antidiabetic and antioxidant activity of Bauhinia rufescens, a plant used in Sudanese folkloric medicine for the treatment of diabetes. It was also aimed to identify isolates and characterize the bioactive antidiabetic and antioxidant compounds using bioactivity-guided fractionation followed by high-performance thin-layer chromatography (HPTLC) autobiography, liquid chromatography-mass spectrometric analysis, and nuclear magnetic resonance (NMR). Two potential compounds were successfully isolated and identified which may provide new leads for more potent analogues in drug discovery.
Elevated Midtrimester Triglycerides as a Biomarker for Postpartum Hyperglycemia in Gestational Diabetes
Authors: Lai Mengyu , Fang Fang , Ma Yuhang , Yang Jiaying , Huang Jingjing , Li Na , Kang Mei , Xu Xianming , Zhang Jiarong , Wang Yufan , Peng Yongde
Published: April 2020

Background. Whether elevated triglyceride (TG) levels during pregnancy were a biomarker for postpartum abnormal glucose metabolism (AGM) in women with previous gestational diabetes mellitus (GDM) remained unknown. The aim of this study was to investigate the association between TG levels during the second trimester and postpartum AGM in GDM women. Methods. This was a retrospective cohort study including 513 GDM women. A 75 g oral glucose tolerance test (OGTT) was performed, and lipid levels were determined during pregnancy and the postpartum period. GDM patients were categorized into tertiles according to their TG levels at 24–28 weeks of gestation (TG<2.14 mmol/L, TG: 2.14–2.89 mmol/L, and TG>2.89 mmol/L). A logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Results. During pregnancy, women in the high TG tertile showed higher HbA1c levels (5.47±0.58% versus 5.28±0.49%, p=0.006), higher total cholesterol (TC) levels (5.85±1.23 mmol/L versus 5.15±0.97 mmol/L, p=0.026), and higher HOMA-IR (2.36 (1.62-3.45) versus 1.49 (0.97-2.33), p<0.001) than the participants in the low TG tertile. After delivery, the prevalence rates of AGM based on above tertiles of TG levels during pregnancy were 26.90%, 33.33%, and 43.27%, respectively (p=0.006). High TG tertile during the second trimester was associated with the presence of postpartum AGM (adjusted OR: 2.001, 95% CI: 1.054-3.800, p=0.034). Conclusions. The elevated midtrimester TG levels were not only accompanied by higher glucose and lipid levels and more severe insulin resistance at the time of the measurement but were a biomarker for postpartum AGM as well.
Efficacy of Amflow®, a Real-Time-Portable Feedback Device for Delivering Appropriate Ventilation in Critically Ill Patients: A Randomised, Controlled, Cross-Over Simulation Study
Authors: Kim Jong Won , Park Sang O , Lee Kyeong Ryong , Hong Dae Young , Baek Kwang Je
Published: April 2020

Objective. The aim of this study was to test whether Amflow® (a newly designed portable ventilation feedback device) can assist rescuers in delivering target tidal volume (VT) and respiration rate (RR) during self-inflating bag (SB) ventilations in various clinical scenarios. Method. This was a simulation study with a prospective cross-over design. A total of 40 trained participants who underwent training for SB ventilation were recruited. Using a SB with or without Amflow® alternately, participants delivered ventilations to test lungs connected to a gas flow analyser in each of three different scenarios: acute respiratory distress syndrome (ARDS; 315–385 ml ranges for 350 ml target VT, with 20 breaths/min); cardiopulmonary resuscitation (CPR; 450–550 ml ranges for 500 ml target VT with 10 breaths/min); and adult head trauma (630–770 ml ranges for 700 ml target VT with 15 breaths/min). Results. The feedback group (SB with Amflow®) demonstrated a significantly higher percentage of delivering the appropriate VT ranges than the no-feedback group for both ARDS (58.6% versus 23.5%, respectively) and CPR (85.4% versus 41.0%, respectively) (all p<0.05). However, there was no significant difference between the two groups in the percentage of delivering the appropriate VT ranges in head trauma patients (65.9% versus 68.3%, respectively; p=0.092). In all three scenarios, a higher percentage of target RR delivered was achieved in the feedback group (88.3%, 99.2%, and 96.3%, respectively) compared with the no-feedback group (5.8%, 12.5%, and 10.0%, respectively) (all p<0.05). Conclusion. The Amflow® device could be useful for rescuers in delivering SB ventilation with appropriate VT and RR simultaneously in various critical situations, except for clinical cases that demand greater delivered VT.
The Combination of CD147 and MMP-9 Serum Levels Is Identified as Novel Chemotherapy Response Markers of Advanced Non-Small-Cell Lung Cancer
Authors: Qiao Xiaojuan , Gu Yan , Yu Jingfeng , Wang Jinghui , Liu Xuan , Gu Meng , Ma Li , Jia Yongfeng , Zhang Shucai
Published: April 2020

To evaluate the correlation between the changes in serum concentrations of cluster of differentiation-147 (scCD147) and chemotherapy outcome in patients with NSCLC and evaluate the combination of scCD147 with serum matrix metalloproteinase-9 (scMMP-9) levels in the prediction of chemotherapy response, eighty-two patients with advanced LC were enrolled. Newly diagnosed cases were treated with platinum-based chemotherapy. We measured scCD147 protein levels in LC cases by ELISA and used receiver operating characteristic (ROC) curves to analyze the results. Four time points were chosen to examine the association between the changes in scCD147 and chemotherapy outcome: before chemotherapy and 21 days after the start of the first, second, and fourth chemotherapy cycles. We assessed the combination of scCD147 and scMMP-9 serum levels in predicting the chemotherapy response. scCD147 was higher in LC cases than that in healthy volunteers (HVs). scCD147 was associated with distant metastases and TNM stage. scCD147 and scMMP-9 appeared to be independent predictive factors for chemotherapy outcomes after the first and second chemotherapy cycles for patients with NSCLC. Multivariable analysis also demonstrated that variations in scCD147 and scMMP-9 could be independent factors for monitoring chemotherapy outcome for patients with NSCLC. Furthermore, when scCD147 and scMMP-9 are combined into a new risk model, it has a markedly better prediction of chemotherapy outcomes than each protein alone. scCD147 and MMP-9 are potential predictive biomarkers for efficacy, and their combination significantly improves the predictive power for chemotherapy response in patients with NSCLC.
PBMCs to Stress‐Associated miR‐18a‐5p and miR‐22‐3p Ratios as New Indicators of Metabolic Syndrome
Authors: Huang Yuxiang , Zhao Liqin , Yan Yuxiang , Chen Jingyu , Liu Pengfei , Xv Weicheng , Qian Ge , Li Chijian , Liang Shiyi , Zou Hequn , Li Yongqiang
Published: April 2020

Purpose. Metabolic syndrome (MetS) is associated with chronic stress. miR‐18a‐5p and miR‐22‐3p are two miRNAs which can target the glucocorticoid receptor. This study looked at the changes in metabolic parameters and the predictive value of the peripheral blood mononuclear cells (PBMCs) to stress‐associated miRNA ratios as new indicators in subjects with and without MetS in southern China. Patients and Methods. There were 81 participants (39 with MetS and 42 without MetS) in this cross‐sectional study. The potential miRNAs were filtrated in the GEO database. The expression of miR‐18a‐5p and miR‐22‐3p in PBMCs was evaluated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The risk of miRNA and PBMCs to stress‐associated miRNA ratios contributing to the presence of MetS was estimated by univariate and multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results. MetS was positively correlated with cortisol, IL‐6, lymphocyte to miR‐18a‐5p ratio (LT18R), lymphocyte to miR‐22‐3p ratio (LT22R), monocyte to miR‐18a‐5p ratio (MT18R), monocyte to miR‐22‐3p ratio (MT22R), PBMCs to miR‐18a‐5p ratio (PT18R), and PBMCs to miR‐22‐3p ratio (PT22R) and negatively associated with the expression levels of miR‐18a‐5p and miR‐22‐3p (P < 0.05). In addition, PT18R (odds ratio: 0.894; 95% CI: 0.823‐0.966; P < 0.001) and PT22R (odds ratio: 0.809; 95% CI: 0.717‐0.900; P < 0.001) were independent predictors of MetS, respectively. A receiver operating characteristic (ROC) curve analysis was performed to assess the value of the PT18R‐PT22R (PMR) panel (odds ratio: 0.905; 95% CI: 0.838‐0.971; P < 0.001) for predicting MetS. The area under the curve yielded a cut‐off value of 0.608, with sensitivity of 74.4% and specificity of 95.2% (P < 0.001). Conclusion. In summary, miR‐18a‐5p and miR‐22‐3p in PBMCs may be important biomarkers of stress reaction and may play a role in vulnerability to MetS. Besides, the inflammatory cells to the two miRNA ratios demonstrated high accuracy in the diagnosis of MetS.
Manganese Neurotoxicity as a Complication of Chronic Total Parenteral Nutrition
Authors: Khan Alisha , Hingre Jonathan , Dhamoon Amit S.
Published: April 2020

Manganese accumulation in the central nervous system creates clinical symptoms of cognitive dysfunction, behavioral changes, and movement disorders resembling Parkinson’s disease. Radiographic features of this rare clinical entity include symmetric T1 hyperintensities in the bilateral globus pallidi, with corresponding hypointensities on T2-weighted images. Total parenteral nutrition (TPN) is an increasingly used potentially lifesaving therapy for patients who cannot tolerate enteral nutrition. However, when used over a period of several weeks to months, its associated risks and complications carry significant morbidity and mortality. One of the more rare complications of TPN use is manganese toxicity. We provided care for a 38-year-old female on chronic TPN who presented to the hospital with Parkinsonian features, confusion, falls, and lethargy. MRI brain showed T1 hyperintensities in the bilateral globus pallidi, which were attributed to manganese toxicity from chronic TPN use. Supporting evidence for this rare entity included decreased signal intensity in the bilateral globus pallidi on T2-weighted images and T1 hyperintensities in the substantia nigra. With antifungal treatment and permanent cessation of TPN, her mentation and neurological symptoms began to improve within a week. Repeat MRI brain performed one month after discontinuation of TPN revealed improvement of the T1 hyperintensities in the bilateral globus pallidi. Our objective in presenting this case is to highlight manganese neurotoxicity as a rare complication of TPN in a patient without known hepatic dysfunction and to emphasize the importance of routinely monitoring patients for the possible adverse effects of chronic TPN. Our case is among the handful of published cases in which a patient without known liver dysfunction, which is the primary organ responsible for manganese elimination from the body, developed manganese neurotoxicity.
Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms
Authors: Gay-Chevallier Servane , de Mestier Louis , Perinel Julie , Forestier Julien , Hervieu Valérie , Ruszniewski Philippe , Millot Ingrid , Valette Pierre-Jean , Pioche Mathieu , Lombard-Bohas Catherine , Subtil Fabien , Adham Mustapha , Walter Thomas
Published: April 2020

Introduction: The characteristics, prognostic factors, and management of duodenal neuroendocrine neoplasms (dNEN) are ill-defined, given their rarity. Whether nonsurgical management might be appropriate for patients with nonmetastatic dNEN and a good prognosis, as is the case for pancreatic NEN (pNEN), is unknown. We aimed to describe the management and prognosis of nonmetastatic dNEN patients. Methods: All consecutive patients with nonmetastatic dNEN managed between 1981 and 2018 in 2 expert centers were included. Recurrence-free survival (RFS) and factors associated with recurrence were estimated. Results: A total of 145 patients with dNEN were included. Twenty-eight patients with sporadic, nonfunctioning, small (median 7 mm) dNEN underwent endoscopic resection, with a 5-year RFS rate of 89.4%. Local recurrence occurred in 2 patients, who underwent surgery with no new events. The 5-year RFS rate was 87.9% in patients who underwent surgery. Upon univariate analysis, age, size, Ki67 index, and lymph node involvement (LN+) were significantly associated with worse RFS for all dNEN treated (endoscopy/surgery); multivariate analysis found that age, size, and LN+ were associated with worse RFS. Conclusion: Selected nonmetastatic dNEN had a favorable outcome, and a less invasive therapeutic strategy appeared more suitable than oncological surgery.
Priorities for Patient‐Centered Research in Valvular Heart Disease: A Report From the National Heart, Lung, and Blood Institute Working Group
Authors: Lindman Brian R. , Arnold Suzanne V. , Bagur Rodrigo , Clarke Lindsay , Coylewright Megan , Evans Frank , Hung Judy , Lauck Sandra B. , Peschin Susan , Sachdev Vandana , Tate Lisa M. , Wasfy Jason H. , Otto Catherine M.
Published: April 2020

Over the past decade, the field of valvular heart disease (
VHD
) has rapidly transformed, largely as a result of the development and improvement of less invasive transcatheter approaches to valve repair or replacement. This transformation has been supported by numerous well‐designed randomized trials, but they have centered almost entirely on devices and procedures. Outside this scope of focus, however, myriad aspects of therapy and management for patients with
VHD
have either no guidelines or recommendations based only on expert opinion and observational studies. Further, research in
VHD
has often failed to engage patients to inform study design and identify research questions of greatest importance and relevance from a patient perspective. Accordingly, the National Heart, Lung, and Blood Institute convened a Working Group on Patient‐Centered Research in Valvular Heart Disease, composed of clinician and research experts and patient advocacy experts to identify gaps and barriers to research in
VHD
and identify research priorities. While recognizing that important research remains to be done to test the safety and efficacy of devices and procedures to treat
VHD
, we intentionally focused less attention on these areas of research as they are more commonly pursued and supported by industry. Herein, we present the patient‐centered research gaps, barriers, and priorities in
VHD
and organized our report according to the “patient journey,” including access to care, screening and diagnosis, preprocedure therapy and management, decision making when a procedure is contemplated (clinician and patient perspectives), and postprocedure therapy and management. It is hoped that this report will foster collaboration among diverse stakeholders and highlight for funding bodies the pressing patient‐centered research gaps, opportunities, and priorities in
VHD
in order to produce impactful patient‐centered research that will inform and improve patient‐centered policy and care.
Neurophysiological Correlates of Frequency, Concreteness, and Iconicity in American Sign Language
Authors: Emmorey Karen , Winsler Kurt , Midgley Katherine J. , Grainger Jonathan , Holcomb Phillip J.
Published: April 2020

To investigate possible universal and modality-specific factors that influence the neurophysiological response during lexical processing, we recorded event-related potentials while a large group of deaf adults ( n = 40) viewed 404 signs in American Sign Language (ASL) that varied in ASL frequency, concreteness, and iconicity. Participants performed a go/no-go semantic categorization task (does the sign refer to people?) to videoclips of ASL signs (clips began with the signer’s hands at rest). Linear mixed-effects regression models were fit with per-participant, per-trial, and per-electrode data, allowing us to identify unique effects of each lexical variable. We observed an early effect of frequency (greater negativity for less frequent signs) beginning at 400 ms postvideo onset at anterior sites, which we interpreted as reflecting form-based lexical processing. This effect was followed by a more widely distributed posterior response that we interpreted as reflecting lexical-semantic processing. Paralleling spoken language, more concrete signs elicited greater negativities, beginning 600 ms postvideo onset with a wide scalp distribution. Finally, there were no effects of iconicity (except for a weak effect in the latest epochs; 1,000–1,200 ms), suggesting that iconicity does not modulate the neural response during sign recognition. Despite the perceptual and sensorimotoric differences between signed and spoken languages, the overall results indicate very similar neurophysiological processes underlie lexical access for both signs and words.
The “World Café” as a Participatory Method for Collecting Qualitative Data
Authors: Löhr Katharina , Weinhardt Michael , Sieber Stefan
Published: April 2020

We introduce and discuss “World Café” (WC), a participatory assessment tool widely used in community development and organizational change processes, as additional qualitative research method. We propose WC as a participatory method of data collection for a large group of participants, discussing its strengths and weaknesses in comparison to semistructured interviews and focus groups, two well-established methods in qualitative research. As a research method, we find that WC complements other methods in important ways. When there are many participants, it helps guide the exploration and verification of themes. Integrating the method into the research design may help increase both the reference sample and the level of participation. Furthermore, as a participatory method, it not only produces data for the researchers but also has the potential to benefit the participants, as it facilitates dialogue and mutual learning, thus motivating their participation and responses.
Developing Action Plans in Youth Photovoice to Address Community-Level HIV Risk in Rural Malawi
Authors: Lofton Saria , Norr Kathleen F. , Jere Diana , Patil Crystal , Banda Chimwemwe
Published: April 2020

Youth-driven approaches to HIV prevention can engage youth and improve health outcomes. Photovoice has been used to engage youth in identifying the assets and challenges in their communities. In sub-Saharan Africa, youth remain vulnerable to HIV infection. This article describes a photovoice project, named Youth Photovoice, conducted in rural Malawi, which focused on community places and situations relating to risky sexual behaviors that place youth at risk of HIV infection. Twenty-four youth, ages 13–17 (12 males and 12 females), participated in Youth Photovoice. During the photovoice process, youth identified five community situations and places that put them at risk of unsafe sex and thus HIV infection: initiation ceremonies, isolated places, community celebrations, local businesses such as bars and rest houses, and church-sponsored activities. Youth used a systematic action planning process to develop action plans. They presented their action plans to local leaders and parents. Parents and leaders responded positively and agreed to help the youth carry out their plans. If their plans to address community situations that put them at risk of unsafe sex succeed, there will be a direct impact on reducing the risk of HIV infection among youth. Youth Photovoice provided the opportunity for youth to obtain new skills, build new partnerships, and present their ideas to community leaders. Integrating this action planning process into photovoice helped to guide the youth toward actualizing their HIV prevention plans in their community. This process can increase the effectiveness of photovoice initiatives to address other community issues in a wide variety of settings.
A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD–mutant acute myeloid leukemia
Authors: Smith Catherine C. , Levis Mark J. , Frankfurt Olga , Pagel John M. , Roboz Gail J. , Stone Richard M. , Wang Eunice S. , Severson Paul L. , West Brian L. , Le Mai H. , Kayser Sabine , Lam Bao , Hsu Henry H. , Zhang Chao , Bollag Gideon , Perl Alexander E.
Published: April 2020

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI–resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD–mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. Plasma inhibitory assay demonstrated that patients dosed with ≥3000 mg had sufficient levels of active drug in their trough plasma samples to achieve 95% inhibition of FLT3 phosphorylation in an FLT3-ITD AML cell line. Based on a plateau in drug exposure, the 3000-mg dose was chosen as the recommended phase 2 dose. The most frequently reported treatment-emergent adverse events were diarrhea (50%), fatigue (47%), and nausea (46%). Based on modified response criteria, the overall response rate to pexidartinib among all patients was 21%. Twenty-three percent of patients treated at ≥2000 mg responded. The overall composite complete response rate for the study was 11%. Six patients were successfully bridged to transplantation. Median overall survival (OS) of patients treated in dose expansion was 112 days (90% confidence interval [CI], 77-150 days), and median OS of responders with complete remission with or without recovery of blood counts was 265 days (90% CI, 170-422 days). This trial was registered at www.clinicaltrials.gov as #NCT01349049.
First report of tethered cord syndrome in a patient with Sotos syndrome
Authors: Kuzucu Pelin , Türkmen Tolga , Börcek Alp Özgün
Published: April 2020

Background

Sotos syndrome is caused by a gene deletion with an autosomal dominant pattern of inheritance. The Sotos syndrome was first described by Juan Sotos. Cole and Hughes identified the clinical characteristics of this syndrome. This syndrome is characterized by macrocephaly, frontal bossing, ocular hypertelorism, overgrowth, subdural hygroma, ventricular dilatation, agenesis of the corpus callosum. This syndrome is associated with mutations in NSD 1 (nuclear receptor SET domain-containing protein 1) gene, protein insufficiency, and a 5q35 microdeletion. Sotos syndrome is reported to occur in approximately 1/10,000–15,000 births.

Case presentation

We present a patient with Sotos syndrome who is harboring a sacral lipoma and tethered cord syndrome and she had growth retardation, frontal bossing and hypertelorism. After a standard approach for tethered cord syndrome, the patient was discharged 3 days after without any additional neurodeficits.

Conclusion

In the literature, sacral lipoma and tethered cord syndrome with Sotos syndrome have not been published yet.
The associations of sugar-sweetened, artificially sweetened and naturally sweet juices with all-cause mortality in 198,285 UK Biobank participants: a prospective cohort study
Authors: Anderson Jana J. , Gray Stuart R. , Welsh Paul , Mackay Daniel F. , Celis-Morales Carlos A. , Lyall Donald M. , Forbes John , Sattar Naveed , Gill Jason M. R. , Pell Jill P.
Published: April 2020

Background

Recent efforts to address the obesity epidemic have focused on sugar consumption, especially sugar-sweetened beverages. However, sugar takes many forms, is only one contributor to overall energy consumption and is correlated with other health-related lifestyle factors. The objective was to investigate the associations with all-cause mortality of sugar- and artificially sweetened beverages and naturally sweet juices.

Methods

Setting: UK Biobank, UK. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016; 198,285 men and women aged 40–69 years were eligible for this study (40% of the UK Biobank), of whom 3166 (1.6%) died over a mean of 7 years follow-up. Design: prospective population-based cohort study. Exposure variables: dietary consumption of sugar-sweetened beverages, artificially sweetened beverages, naturally sweet juices (100% fruit/vegetable juices) and total sugar intake, self-reported via 24-h dietary assessment tool completed between 2009 and 2012. Main outcome: all-cause mortality. Cox regression analyses were used to study the association between the daily intake of the above beverages and all-cause mortality. Models were adjusted for sociodemographic, economic, lifestyle and dietary confounders.

Results

Total energy intake, total sugar intake and percentage of energy derived from sugar were comparable among participants who consumed > 2/day sugar-sweetened beverages and > 2/day fruit/vegetable juices (10,221 kJ/day versus 10,381 kJ/day; 183 g versus 190 g; 30.6% versus 31.0%). All-cause mortality was associated with total sugar intake (highest quintile adj. HR 1.28, 95% CI 1.06–1.55) and intake of sugar-sweetened beverages (> 2/day adj. HR 1.84, 95% CI 1.42–2.37) and remained so in sensitivity analyses. An association between artificially sweetened beverage intake and mortality did not persist after excluding deaths in the first 2 years of follow-up (landmark analysis) nor after excluding participants with recent weight loss. Furthermore, the inverse association between fruit/vegetable juice intake and mortality did not persist after additional adjustment for a diet quality score.

Conclusions

Higher mortality is associated with sugar-sweetened beverages specifically. The lack of an adverse association with fruit/vegetable juices suggests that source of sugar may be important and the association with artificially sweetened beverage may reflect reverse causation.
Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats
Authors: Abekura Yu , Ono Isao , Kawashima Akitsugu , Takizawa Katsumi , Koseki Hirokazu , Miyata Haruka , Shimizu Kampei , Oka Mieko , Kushamae Mika , Miyamoto Susumu , Kataoka Hiroharu , Ishii Akira , Aoki Tomohiro
Published: April 2020

Background

As subarachnoid hemorrhage due to rupture of an intracranial aneurysm (IA) has quite a poor outcome despite of an intensive medical care, development of a novel treatment targeting unruptured IAs based on the correct understanding of pathogenesis is mandatory for social health.

Methods

Using previously obtained gene expression profile data from surgically resected unruptured human IA lesions, we selected G-protein coupled receptor 120 (GPR120) as a gene whose expression is significantly higher in lesions than that in control arterial walls. To corroborate a contribution of GPR120 signaling to the pathophysiology, we used an animal model of IAs and examine the effect of a GPR120 agonist on the progression of the disease. IA lesion was induced in rats through an increase of hemodynamic stress achieved by a one-sided carotid ligation and induced hypervolemia. Eicosapentaenoic acid (EPA) was used as an agonist for GPR120 in this study and its effect on the size of IAs, the thinning of media, and infiltration of macrophages in lesions were examined.

Result

EPA administered significantly suppressed the size of IAs and the degenerative changes in the media in rats. EPA treatment also inhibited infiltration of macrophages, a hallmark of inflammatory responses in lesions. In in vitro experiments using RAW264.7 cells, pre-treatment of EPA partially suppressed lipopolysaccharide-induced activation of nuclear factor-kappa B and also the transcriptional induction of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant for macrophages to accumulate in lesions. As a selective agonist of GPR120, TUG-891, could reproduce the effect of EPA in RAW264.7 cells, EPA presumably acted on this receptor to suppress inflammatory responses. Consistently, EPA remarkably suppressed MCP-1 expression in lesions, suggesting the in vivo relevance of in vitro studies.

Conclusions

These results combined together suggest the potential of the medical therapy targeting GPR120 or using EPA to prevent the progression of IAs.
Improving the treatment of pre-operative anemia in hepato-pancreato-biliary patients: a quality improvement initiative
Authors: Zwiep Terry M. , Gilbert Richard W. D. , Moloo Husein , Touchie Donna , Martel Guillaume , Wallace Tom , Bertens Kimberly A.
Published: April 2020

Background

Pre-operative anemia is a common, but treatable, condition encountered by surgical patients. It has been associated with increased perioperative complications, length of stay, and blood transfusions. The aim of this project was to increase the treatment rate of pre-operative anemia to 75% of patients consented for major hepato-pancreato-biliary (HPB) surgery.

Methods

This was an interrupted time series study and a spread initiative from a similar project in a colorectal surgery population. Interventions included an anemia screening and treatment algorithm, standardized blood work, referral to a patient blood management program, and standardized oral iron prescriptions. The primary outcome measure was the change in pre-operative anemia treatment rate and the secondary outcome measure was the post treatment increase in hemoglobin.

Results

A total of 208 patients were included (n = 124 pre-intervention and n = 84 post-intervention). Anemia was present in 39.9% of patients. The treatment rate of pre-operative anemia increased to 44.1% from 28.6%. The mean hemoglobin increased from 110 g/L to 119 g/L in patients who were treated (p = 0.03). There was no significant increase or decrease in blood transfusions or mean number of red cell units transfused per patient. Screening rates for pre-operative anemia increased from 41.1 to 64.3% and appropriate referrals to the patient blood management program increased from 14.3 to 67.6%.

Conclusions

This study demonstrates a small scale spread initiative focused on the treatment of pre-operative anemia. Although the goal to treat 75% of anemic patients was not reached, an effective referral pathway to an existing patient blood management program was developed, and a significant increase in the mean hemoglobin in anemic patients who have been treated pre-operatively was demonstrated.