bluuebunny/crossref_metadata_2025 huggingface dataset:
The Preconditioning of Busulfan Promotes Efficiency of Human CD133+ Cells Engraftment in NOD Shi-SCID IL2Rγcnull (NOG) Mice via Intra-Bone Marrow Injection
Authors: Guo Xiaofang , Yin Xiaoxiao , Zhu Wenjuan , Pan Ying , Wang Hui , Liang Yinming , Zhu Xiaofei
Published: April 2019

Human CD133+ stem cells were injected into the bone marrow cavity of NOG (NOD Shi-SCID IL2Rγcnull) mice with or without preconditioning of busulfan in order to assess the efficiency of human CD133+ cells engraftment. Peripheral blood from CD133+-engrafted NOG mice was analyzed by flow cytometry. The results showed that human CD19+ B lymphocytes could be detected at 4 weeks post-transplantation, and human CD4+, CD8+ subsets of T lymphocytes, CD19– CD14– HLA-DR+ DCs and CD19– CD14+ monocytes could be detected at 16 weeks post-transplantation. The survival rate of mice in busulfan-untreated group (100%) was slightly higher than that in the busulfan-pretreated group (83%) ( P > 0.05). However, the differentiation efficiency of CD133+ stem cells in busulfan-pretreated group was significantly higher than that in the untreated group ( P < 0.05). This data imply that CD133+ cells could be a good resource for a humanized mouse model, and the preconditioning of busulfan could be more conducive to accelerating the differentiation of human CD133+ cells in NOG mice by intra-bone marrow injection.
Book review: Akshaya Mukul, Gita Press and the Making of Hindu India
Authors: Kumar Manoj
Published: April 2019

Akshaya Mukul, Gita Press and the Making of Hindu India. Noida: HarperCollins Publishers India, The New India Foundation, 2015. 540 pp., ₹799 (hardbound). ISBN: 139789351772309; 109351772306.
Effects and safety of separate low-dose hydrocortisone use in patients with septic shock: A meta-analysis
Authors: Wu Jing , Huang Man , Wang QianWen , Ma Yuefeng , Jiang Libing
Published: April 2019

Objective:

The aim of this study was to explore the effects and safety of low-dose hydrocortisone in patients with septic shock.

Methods:

The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched from database inception until 1 August 2018. Two reviewers performed literature selection, data extraction, and quality evaluation independently.

Results:

Twelve randomized controlled trials were included in this meta-analysis. The combined results showed that low-dose hydrocortisone use had no survival benefit in patients with septic shock (relative risk = 1.09; 95% confidence interval = 0.88–1.05; P = 0.37). But low-dose hydrocortisone use was useful for shock reverse (relative risk = 1.09; 95% confidence interval = 1.00–1.19; P = 0.04) and in shortening the time of vasopressor support (weighted mean difference = −1.79, 95% confidence interval = −2.05 to −1.52; P < 0.00001). In addition, use of low-dose hydrocortisone was associated with a higher risk of hyperglycemia (relative risk = 1.21; 95% confidence interval = 1.04–1.40; P = 0.01) and hypernatremia (relative risk = 6.34; 95% confidence interval = 1.19–33.81; P = 0.03). There was no significant improvement of intensive care unit mortality (relative risk = 1.11; 95% confidence interval = 0.93–1.33; P = 0.23) or hospital mortality (relative risk = 1.08; 95% confidence interval = 0.94–1.24; P = 0.29), length of intensive care unit (weighted mean difference = −1.84; 95% confidence interval = −5.80 to 2.11; P = 0.36) or length of hospital (weighted mean difference = 0.11; 95% confidence interval = −2.06 to 2.29; P = 0.98), and time of mechanical support (weighted mean difference = −0.69; 95% confidence interval = −1.76 to −0.38; P = 0.20) with the use of low-dose hydrocortisone. There was no significant difference in secondary infection (relative risk = 1.04; 95% confidence interval = 0.91–1.18; P = 0.57), recurrence of shock (relative risk = 1.47; 95% confidence interval = 0.64–3.39; P = 0.36), and gastrointestinal bleeding (relative risk = 1.41; 95% confidence interval = 0.89–2.22; P = 0.14) with the use of low-dose hydrocortisone.

Conclusion:

Although there was no effect of low-dose hydrocortisone on survival of patients with septic shock, it is associated with a higher rate of shock reversal and shortening duration of vasopressor support; thus, low-dose hydrocortisone may be an alternative drug in septic shock patients who are refractory to fluid resuscitation and vasopressors.
A young lady with right peripheral facial palsy
Authors: Lau James Siu Ki , Chan Puisy Yau Ng , Kan Pui Gay
Published: April 2019

A common diagnosis to patients with sudden onset of peripheral facial paralysis is Bell’s palsy. However, when there are other clinical features, such as increased intracranial pressure or bidirectional nystagmus, one must consider central causes. This report illustrates the importance of detailed observation and identification of nystagmus in arriving at an accurate clinical diagnosis.
Optic nerve sheath diameter as a predictor of acute cerebellar infarction in acute vertigo patients without brain computed tomography abnormalities
Authors: You Myoung Sun , Lee Sun Hwa , Yun Seong Jong , Ryu Seokyong , Choi Seung Woon , Kim Hye Jin , Kang Tae Kyung , Oh Sung Chan , Cho Suk Jin
Published: April 2019

Background and objectives:

To date, no study has investigated the ability of optic nerve sheath diameter calculated from non-contrast brain computed tomography to predict acute cerebellar infarction in patients with acute vertigo. The aim of our study was to evaluate the predictive utility of optic nerve sheath diameter for diagnosing acute cerebellar infarction in patients with acute vertigo without computed tomography abnormalities.

Methods:

We retrospectively enrolled patients with acute vertigo without computed tomography abnormalities who underwent magnetic resonance imaging including diffusion-weighted imaging at our emergency department between January 2016 and December 2017. Two emergency physicians independently measured optic nerve sheath diameter at 3 mm (ONSD3) and 10 mm (ONSD10) behind the globe in each patient. Final magnetic resonance imaging reports with clinical progress notes were used as the reference standard. A multivariate logistic regression analysis, receiver operating characteristic curves, and intra-class correlation coefficients were calculated to estimate predictive value.

Results:

A total of 34 patients (16.1%) were diagnosed with acute infarction and 177 patients (83.9%) were diagnosed with peripheral vertigo. Mean ONSD3 ( p < 0.001) and ONSD10 ( p < 0.001) were independent predictive factors for distinguishing acute infarction and peripheral vertigo. ONSD3 (cut-off = 4.22 mm) had 100% (95% confidence interval = 89.7–100.0) sensitivity and 97.7% (95% confidence interval = 95.1–99.6) specificity with area under the receiver operating characteristic curve of 0.988 (95% confidence interval = 0.978–1.0), while ONSD10 (cut-off = 3.63 mm) had 100% (95% confidence interval = 89.7–100.0) sensitivity and 87.6% (95% confidence interval = 81.8–92.0) specificity with area under the receiver operating characteristic curve of 0.976 (95% confidence interval = 0.959–0.997). There were good inter- and intra-observer agreements for both sides of ONSD3 and ONSD10 (intra-class correlation coefficient range = 0.652–0.773).

Conclusion:

Optic nerve sheath diameter, in particular OSND3, is a feasible predictive marker for acute infarction in patients with acute vertigo without computed tomography abnormalities. This information can assist decision-making in ordering brain magnetic resonance imaging for the assessment of acute vertigo.
Impact on Healthy Behaviors of Group Obesity Management Visits in Middle School Health Centers
Authors: Schapiro Naomi A. , Green Emily K. , Kaller Shelly , Brindis Claire D. , Rodriguez Atziri , Alkebulan-Abakah Mizan , Chen Jyu-Lin
Published: April 2019

This mixed-methods community-based participatory pilot study examined the feasibility and preliminary efficacy of group obesity management visits offered through school-based health centers. The study was implemented through an academic–community partnership in three school health centers serving primarily Latinx and African American youth. Participants ( n = 71) completed pre- and post-surveys about intention to change diet and exercise habits, knowledge and self-efficacy related to healthy eating, and social support. Focus groups were conducted after the intervention and 18 months later. Group visits were feasible and highly valued by study participants. Quantitative results showed a significant decrease in soda consumption, increased support from classmates, and an increased number of exercise days. In focus groups, youth endorsed cooking, tasting, and shopping activities, noted the importance of family involvement in behavior change, and stated that stress reduction mindfulness exercises helped to change eating habits. Implications for school-based health care and school nursing are discussed.
School Nurse Websites: What Do They Tell Us About School Nurses?
Authors: Moss Eileen , Bergren Martha Dewey , Maughan Erin D.
Published: April 2019

Problem:

Stakeholders often misunderstand the role of the school nurse resulting in underutilization or elimination of school nurse positions. Social media and school nurse websites are recommended to increase school nurse visibility and change the public narrative of school nursing.

Objective:

The objective of this needs assessment is to determine whether school nurses are using web presence to increase their visibility to affect the narrative of school nursing.

Method:

An evaluation was conducted to determine the presence and content of school nurse websites in 50 schools and their school districts across the nation.

Results:

Fewer than one third of school nurses have websites, three fourths of districts have a school district health websites, and there was no evidence of a nurse in 10% of the school websites assessed.

Anticipated Contribution to Practice:

The needs assessment determined that nurses are not maximizing school websites to communicate their role to stakeholders.
Isolation, Characterization, and Genomic Analysis of Pseudomonas sp. Strain SMT-1, an Efficient Fluorene-Degrading Bacterium
Authors: Desta Mulugeta , Wang Weiwei , Zhang Lige , Xu Ping , Tang Hongzhi
Published: April 2019

Comprehensive study of novel microbial organisms capable of degrading fluorene is crucial to develop essential strategies for further application on enhanced bioremediation technologies. Many fluorene-degrading bacteria have been studied; however, little information about the genome sequences of these organisms, which would facilitate investigation of the molecular mechanisms of fluorene degradation, is available. In this study, a bacterial strain designated SMT-1, which uses fluorene as its sole carbon source, was isolated from Laogang landfill in Shanghai, People’s Republic of China, and identified as a Pseudomonas sp., based on 16S rRNA gene sequence analysis. Maximum growth and degrading activity of strain SMT-1 were observed at 30°C, pH 7.0 and 200 r/min in mineral salt medium containing 0.4 mm fluorene. We obtained a draft genome sequence of strain SMT-1 to gain insight into the genetic mechanisms for the degradation of aromatic compounds. Sequences greater than 1 kb in length were obtained by Illumina sequencing; strain SMT-1 was found to contain 5542 predicted genes. This working draft genome comprises 68 contigs and DNA scaffolds and has a total size of 6 108 237 bp and a calculated G + C content of 61.59%. Amino acid metabolism clusters were enriched in SMT-1 genes annotation, with the highest abundant observed for the “ABC transporters” subcategories, followed by transcription, energy production and conversion, and inorganic ion transport and metabolism. The genomic information for SMT-1 provides a useful resource for elucidating the molecular mechanism of fluorene catabolism.
Norm emergence as agenda diffusion: Failure and success in the regulation of cluster munitions
Authors: Rosert Elvira
Published: April 2019

The research on international norms offers several models of their evolution; however, a convincing model specifically depicting the phase of norm emergence is still lacking. Macro models (e.g. the norm life cycle) focus on the overall evolution of norms and distinguish the emergence phase as one among others, but they remain too rough. Meso models focus on a specific phase, but on phases other than norm emergence, such as diffusion (e.g. the signalling model) or enforcement (e.g. the spiral model). If they do focus on emergence, this focus remains case-specific and lacks theorisation. Micro models (e.g. the persuasion model or the funnelling model) focus on specific sequences within a phase. In this article, I develop one model of norm emergence by conceptualising it as the diffusion of a problem through different agendas and the discursive transformation of a problem into a (problem-solving) norm. The model distinguishes four sequences of norm emergence: problem adoption by norm entrepreneurs; issue creation in the public sphere; candidate norm creation in the institutional-deliberative sphere; and norm creation in multilateral negotiations. I illustrate the utility of this model by tracing the emergence of the norm against cluster munitions.
Expenditure-based segmentation of tourists taking into account unobserved heterogeneity: The case of Venice
Authors: Mortazavi Reza , Lundberg Magdalena
Published: April 2019

Visitors to big tourist cities are very likely heterogeneous and can be classified into different segments, for example, low and high spenders. Previous studies on visitor expenditure-based segmentation seem to have only taken into account observed heterogeneity, usually segmenting tourists based on observed characteristics. In the present study, however, the visitors to Venice, Italy, are segmented with respect to their spending into different groups based on both observed and unobserved heterogeneity using a finite mixture model. The results indicate that the visitors belong to three latent classes with respect to their expenditure. Interestingly, different variables affect expenditure differently depending on the latent class belonging. The overall conclusion is that segmenting tourists into different classes based on unobserved heterogeneity with respect to their spending is preferable and more informative than treating the visitors as one homogeneous group. The approach is also more useful for different types of policymaking.
An overview of 38 least squares–based frameworks for structural damage tomography
Authors: Smyl Danny , Bossuyt Sven , Ahmad Waqas , Vavilov Anton , Liu Dong
Published: April 2019

The ability to reliably detect damage and intercept deleterious processes, such as cracking, corrosion, and plasticity are central themes in structural health monitoring. The importance of detecting such processes early on lies in the realization that delays may decrease safety, increase long-term repair/retrofit costs, and degrade the overall user experience of civil infrastructure. Since real structures exist in more than one dimension, the detection of distributed damage processes also generally requires input data from more than one dimension. Often, however, interpretation of distributed data—alone—offers insufficient information. For this reason, engineers and researchers have become interested in stationary inverse methods, for example, utilizing distributed data from stationary or quasi-stationary measurements for tomographic imaging structures. Presently, however, there are barriers in implementing stationary inverse methods at the scale of built civil structures. Of these barriers, a lack of available straightforward inverse algorithms is at the forefront. To address this, we provide 38 least-squares frameworks encompassing single-state, two-state, and joint tomographic imaging of structural damage. These regimes are then applied to two emerging structural health monitoring imaging modalities: Electrical Resistance Tomography and Quasi-Static Elasticity Imaging. The feasibility of the regimes are then demonstrated using simulated and experimental data.
Upper-Extremity Nerve Decompression Under Local Anesthesia: A Systematic Review of Methods for Reduction of Postoperative Pain and Opioid Consumption
Authors: Chocron Yehuda , Aljerian Albaraa , Thibaudeau Stephanie
Published: April 2019

Background: Opioid abuse is a major health concern in North America. Data have shown an alarming increase in opioid-related deaths and complications, which has shed light on current prescription practices across many specialties, including hand surgery. To that end, we sought to conduct a focused literature review to determine the available modalities to decrease postoperative pain and opioid consumption following upper-extremity nerve decompression procedures, taking advantage of the homogeneity and inherent pain pathways of this specific patient cohort. Methods: A systematic review of the literature was conducted. Primary studies evaluating perioperative and intraoperative modalities for postoperative pain reduction and analgesic consumption following upper-extremity nerve decompression procedures under local anesthesia were included. Studies implementing modalities requiring non–hand surgeon expertise (ie, intravenous sedation), as well as studies that include non–nerve decompression procedures, were excluded. Results: A total of 1478 studies were identified, and 9 studies were included after full-text review. Six studies evaluated intraoperative and 3 studies evaluated preoperative and postoperative modalities. Successful interventions included buffered anesthetic, the use of hyaluronidase, and varying techniques and mixtures for anesthetic administration. No successful preoperative or postoperative modalities were identified. Conclusion: Despite data reporting on the dangers associated with current opioid prescription practices, evidence-based modalities to decrease postoperative pain and opioid consumption are limited in general. Several intraoperative modalities do exist, and nonopioid oral analgesics, standardized opioid protocols, and reduced postoperative prescriptions can be used. Large randomized controlled trials evaluating perioperative modalities for pain reduction are needed to further address this issue.
Modeling and experimental analysis of cutting force in longitudinal–torsional ultrasonic-assisted milling of titanium
Authors: Wang Xiaobo , Jiao Feng , Zhao Chongyang , Zhao Bo
Published: April 2019

This study proposed a novel milling technology assisted by longitudinal–torsional compound ultrasonic vibration to overcome the difficulties in the processing of Ti-alloy heterogeneous surfaces or molding surfaces. Using the ball-end milling cutter as the research object, the geometrical model of the milling cutter edge was established, in which an axial position angle was used as the main parameter. The instantaneous cutting thickness was derived based on the cutter path and the cutting force model of the ball-head milling cutter under the longitudinal–torsional compound vibration condition. Finally, using the longitudinal–torsional synchronous vibration cutter system with a resonant frequency of 35.476 kHz and a longitudinal-to-torsional vibration amplitude ratio of approximately 0.25, the milling characteristics of fixed-curvature Ti-alloy workpieces under the longitudinal–torsional compound ultrasonic vibration condition were examined. Results show that the application of the longitudinal–torsional compound ultrasonic vibration can remarkably reduce the radial force Fx but impose almost no effects on the tangential force Fy and the axial force Fz.
Multi-objective optimization of urban road intersection signal timing based on particle swarm optimization algorithm
Authors: Jia Hongfei , Lin Yu , Luo Qingyu , Li Yongxing , Miao Hongzhi
Published: April 2019

Currently, signal control mode is the main control method of urban road intersections. Given that the traffic efficiency of road intersections is mainly affected by signal timing schemes, it is important to optimize signal timing at road intersections. Therefore, signal timing optimization methods of urban road intersections are explored in this work. When optimizing the timing of the signal at the intersections, the selection of optimization targets play an important role. At present, there are multiple objectives considered while designing signal timing scheme, including capacity, delays, and automobile exhaust. However, from the perspective of the traveler, they are more concerned about their own delay while passing intersections. In this work, we propose a novel multi-objective signal timing optimization model with goals of per capita delay, vehicle emissions, and intersection capacity. Considering the problem characteristics of the target problem, a meta-heuristic algorithm combining difference operator, which is based on Particle Swarm Optimization Algorithm, is developed. To test the validity of proposed approach, we applied it to real-world intersection signal timing problems in China. The results show that the optimized signal timing scheme obtained by the proposed algorithm is better than the realistic one. Also, the effectiveness of the developed algorithm is demonstrated by comparing it with other efficient algorithms.
Electroacupuncture downregulates P2X3 receptor expression in dorsal root ganglia of the spinal nerve-ligated rat
Authors: Liang Yi , Gu Yanping , Shi Renyi , Li Guangwen , Chen Yong , Huang Li-Yen Mae
Published: April 2019

Electroacupuncture has been shown to effectively reduce chronic pain in patients with nerve injury. The underlying mechanisms are not well understood. Accumulated evidence suggests that purinergic P2X3 receptors (P2X3Rs) in dorsal root ganglion neurons play a major role in mediating chronic pain associated with nerve injury. The aim of this study is to determine if electroacupuncture stimulation alters P2X3R activity in dorsal root ganglia to produce analgesia under neuropathic pain condition. Peripheral neuropathy was produced by ligation of the left lumbar 5 (L5) spinal nerve in rats. Low-frequency (2 Hz) electrical stimulation was applied to ipsilateral ST36 and BL60 acupoints in rats. The P2X3R agonist (α,β-meATP)-induced flinch responses were reduced after electroacupuncture treatment. Western analyses showed that P2X3R expression was upregulated in nerve-uninjured lumbar 4 (L4) dorsal root ganglion neurons ipsilateral to the spinal nerve ligation. Electroacupuncture-stimulation reversed the upregulation. In nerve-injured L5 dorsal root ganglia, P2X3R expression was substantially reduced. Electroacupuncture had no effect on the reduction. We also determined the injury state of P2X3R expressing dorsal root ganglion neurons using the neuronal injury marker, activating transcription factor 3 (ATF3). Immunohistochemical assay showed that in L4 dorsal root ganglia, almost all P2X3Rs were expressed in uninjured (ATF3−) neurons. Spinal nerve ligation increased the expression of P2X3Rs. Electroacupuncture reduced the increase in P2X3R expression without affecting the percentage of ATF + neurons. In ipsilateral L5 dorsal root ganglion neurons, spinal nerve ligation reduced the percentage of P2X3R + neurons and markedly increased the percentage of ATF3 + cells. Almost all of P2X3Rs were expressed in damaged (ATF3+) neurons. Electroacupuncture had no effect on spinal nerve ligation-induced changes in the percentage of P2X3R or percentage of ATF3 + cells in L5 dorsal root ganglia. These observations led us to conclude that electroacupuncture effectively reduces injury-induced chronic pain by selectively reducing the expression of P2X3Rs in nerve-uninjured L4 dorsal root ganglion neurons.
Baseline history of patients using selexipag for pulmonary arterial hypertension
Authors: Highland Kristin B. , Hull Michael , Pruett Janis , Elliott Caitlin , Tsang Yuen , Drake William
Published: April 2019

Introduction:

Since its introduction to the market in 2016, selexipag has been an alternative oral therapy among both treatment-naïve patients and those with mono or dual therapy failure; however, limited information is available regarding the presentation and management of patients with pulmonary arterial hypertension (PAH) prior to selexipag initiation. This study examined treatment patterns, healthcare utilization, and costs in the 12 months prior to and the 6 months following selexipag initiation.

Methods:

This was a retrospective study of adult commercial and Medicare Advantage with Part D (MAPD) health plan members with a medical or pharmacy claim for selexipag from 1 January 2016 through 31 May 2017, a diagnosis of pulmonary hypertension, and continuous health plan enrollment for 12 months prior to selexipag initiation (baseline period). Treatment patterns, healthcare utilization, and costs were measured over the baseline period and the 6 months following selexipag initiation (among patients with ⩾6 months of follow up).

Results:

After inclusion and exclusion criteria were applied, 95 patients were included in the analysis. At study start, 57.9% of patients were prescribed combination therapy, increasing to 69.5% immediately prior to selexipag initiation. Approximately 60% of patients had one baseline regimen. Emergency visits and inpatient admissions during the baseline period occurred in 63.2% and 48.4% of patients, respectively. Baseline medical costs rose steadily, increasing 266.8% in commercial and 26.7% in MAPD enrollees from the beginning to the end of the 12-month baseline period. PAH-related healthcare costs accounted for more than 80% of total costs. Mean medical costs in the 6 months following selexipag initiation were US$17,215 in commercial and US$23,976 in MAPD enrollees.

Conclusions:

The majority of patients with PAH remained on the same therapy in the 12 months prior to selexipag initiation despite high rates of healthcare utilization and increasing costs. Mean medical costs appeared to decrease after adding or switching to selexipag.
Comparison of toxicity and effectiveness between fixed-dose and body surface area-based dose capecitabine
Authors: de Man Femke M. , Veerman G.D. Marijn , Oomen-de Hoop Esther , Deenen Maarten J. , Meulendijks Didier , Mandigers Caroline M.P.W. , Soesan Marcel , Schellens Jan H.M. , van Meerten Esther , van Gelder Teun , Mathijssen Ron H.J.
Published: April 2019

Background:

Capecitabine is generally dosed based on body surface area (BSA). This dosing strategy has several limitations; however, evidence for alternative strategies is lacking. Therefore, we analyzed the toxicity and effectiveness of fixed-dose capecitabine and compared this strategy with a BSA-based dose of capecitabine in a large set of patients.

Methods:

Patients treated with fixed-dose capecitabine between 2003 and 2015 were studied. A comparable group of patients, dosed based on BSA, was chosen as a control cohort. A total of two combined scores were used: capecitabine-specific toxicity (diarrhea, National Cancer Institute Common Toxicity Criteria grade ⩾3, hand-foot syndrome ⩾2, or neutropenia ⩾2), and clinically relevant events due to toxicity, that is, hospital admission, dose reduction, or discontinuation. Per treatment regimen, patients were divided into three BSA groups based on BSA quartiles corrected for sex. Toxicity scores were compared by a Chi-square test between cohorts, and within cohorts using BSA groups. Progression-free survival (PFS) was estimated by the Kaplan–Meier method.

Results:

A total of 2319 patients were included (fixed dosed, n = 1126 and BSA-based dose, n = 1193). Overall, four regimens were evaluated: capecitabine-radiotherapy ( n = 1178), capecitabine-oxaliplatin ( n = 519), capecitabine triplet ( n = 181) and capecitabine monotherapy ( n = 441). The incidence of capecitabine-specific toxicity and clinically relevant events was comparable between fixed-dose and BSA-dosed patients, while a small difference (7.1%) in absolute dose was found. Both cohorts showed only a higher incidence of both toxicity scores in the lowest BSA group of the capecitabine-radiotherapy group ( p < 0.05). Subgroups of the fixed-dose cohort analyzed for PFS, showed no differences between BSA groups.

Conclusions:

Fixed-dose capecitabine is as comparably well tolerated and effective as BSA-based dosing and could be considered as a reasonable alternative for BSA-based dosing.
CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products
Authors: Chavez Julio C. , Bachmeier Christina , Kharfan-Dabaja Mohamed A.
Published: April 2019

Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin’s lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.
Barriers to physical activity in patients with pulmonary hypertension
Authors: Cascino Thomas M. , McLaughlin Vallerie V. , Richardson Caroline R. , Behbahani‐Nejad Nilofar , Moles Victor M. , Visovatti Scott H. , Jackson Elizabeth A.
Published: April 2019

Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have low levels of physical activity (PA). Increased PA has health benefits including improved quality of life. This study aimed to identify patient‐perceived barriers to PA that correlate with objectively measured PA in this population. We performed a cross‐sectional survey of 40 patients with PAH and CTEPH. Participants rated how often 15 barriers interfere with being physically active on a 5‐point Likert Scale. The primary outcome measure was PA quantified using the Fitbit Zip activity tracker for two weeks. The primary independent variables were the 15 barriers and a summary score (total average barriers). Separate multivariable linear regressions were performed to assess the association between the 15 barriers and the summary score and PA adjusting for age, sex, and PAH etiology. Of the participants, 85% (34/40) had valid step counts and were included. Of these 34, 85% (n = 29) were female and 91% (n = 31) had PAH. The median (interquartile range [IQR]) number of daily steps was 3913 (2309–6313). The barriers endorsed most strongly were lack of self‐discipline, lack of energy, and lack of interest. In the multivariable analysis, a 1‐unit increase in perceived lack of interest, lack of enjoyment, and lack of skills was associated with a significant decrease in step counts of ‐1414 steps (95% confidence interval [CI] = (−2580 – −248), −1458 steps (−2404 – −511), and −1533 steps (−2910 – −156), respectively. Counseling and interventions aimed at increasing PA in patients with PAH should address interest, enjoyment, and skill development.
Management of women affected by endometriosis: Are we stepping forward?
Authors: Di Guardo Federica , Shah Mohsin , Cerana Maria Cecilia , Biondi Antonio , Karaman Erbil , Török Péter , Yela Daniela A. , Giampaolino Pierluigi , Marín-Buck Alejandro , Laganà Antonio Simone
Published: April 2019

Endometriosis is an estrogen-dependent chronic disease defined by the presence of endometrial-like tissue, glands and stroma in ectopic areas. Among all the pathogenic theories proposed to explain the origin of the disease, a pivotal role for immune, hormonal, and epigenetic disbalances have been hypothesized. Endometriosis affects up to 10%–15% of women in reproductive age and represents one of the most common gynecological causes of severe pelvic pain. The main symptoms reported by patients are dysmenorrhea and deep dyspareunia. Although the histological confirmation has been commonly considered mandatory, to date the possibility offered by the improvement in imagining techniques allows to make a proper diagnosis of the disease in most of the cases. Medical therapy represents only a symptomatic treatment and not the definitive solution. The aim of the hormonal therapy is to abolish the menstrual flow using progestin, oral contraceptives, and gonadotropin-releasing hormone agonists to reduce pelvic pain. Surgical treatment consisting of laparoscopy has the goal of abolishing pain and may be conservative or radical in nature depending on the patients’ desire of spontaneous conception in the future. Radical surgery seems to be associated with a higher percentage of pain relief as well as higher recurrence rates. Due to the worldwide acceptance and the ongoing evolution of minimally invasive surgery to treat both benign and malignant diseases, future investigations may be conducted to consider this approach to save the function of all the organs involved by the disease and to reduce post-operative discomfort and psychological impact.
A Biomechanical Comparison of the Arciero and LaPrade Reconstruction for Posterolateral Corner Knee Injuries
Authors: Treme Gehron P. , Salas Christina , Ortiz Gabriel , Gill George Keith , Johnson Paul J. , Menzer Heather , Richter Dustin L. , Qeadan Fares , Wascher Daniel C. , Schenck Robert C.
Published: April 2019

Background:

Injury to the posterolateral corner (PLC) of the knee requires reconstruction to restore coronal and rotary stability. Two commonly used procedures are the Arciero reconstruction technique (ART) and the LaPrade reconstruction technique (LRT). To the authors’ knowledge, these techniques have not been biomechanically compared against one another.

Purpose:

To identify if one of these reconstruction techniques better restores stability to a PLC-deficient knee and if concomitant injury to the proximal tibiofibular joint or anterior cruciate ligament affects these results.

Study Design:

Controlled laboratory study.

Methods:

Eight matched-paired cadaveric specimens from the midfemur to toes were used. Each specimen was tested in 4 phases: intact PLC (phase 1), PLC sectioned (phase 2), PLC reconstructed (ART or LRT) (phase 3), and tibiofibular (phase 4A) or anterior cruciate ligament (phase 4B) sectioning with PLC reconstructed. Varus angulation and external rotation at 0º, 20º, 30º, 60º, and 90º of knee flexion were quantified at each phase.

Results:

In phase 3, both reconstructions were effective at restoring laxity back to the intact state. However, in phase 4A, both reconstructions were ineffective at stabilizing the joint owing to tibiofibular instability. In phase 4B, both reconstructions had the potential to restrict varus angulation motion. There were no statistically significant differences found between reconstruction techniques for varus angulation or external rotation at any degree of flexion in phase 3 or 4.

Conclusion:

The LRT and ART are equally effective at restoring stability to knees with PLC injuries. Neither reconstruction technique fully restores stability to knees with combined PLC and proximal tibiofibular joint injuries.

Clinical Relevance:

Given these findings, surgeons may select their reconstruction technique based on their experience and training and the specific needs of their patients.
Resistance Exercise Counteracts Tumor Growth in Two Carcinoma Rodent Models
Authors: PADILHA CAMILA S. , TESTA MAYRA T. , MARINELLO POLIANA C. , CELLA PAOLA S. , VOLTARELLI FABRÍCIO A. , FRAJACOMO FERNANDO T. , CECHINI RUBENS , DUARTE JOSÉ ALBERTO R. , GUARNIER FLAVIA A. , DEMINICE RAFAEL
Published: April 2019

Purpose

Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals’ life span.

Methods

Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology.

Results

Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff–Bloom–Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span.

Conclusion

RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.
Things We Do For No Reason: HIT Testing in Low Probability Patients
Authors: Li Amanda , Hicks Lisa K , Fan Eddy
Published: April 2019

Inspired by the ABIM Foundation's Choosing Wisely® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.
Critical Errors in Inhaler Technique among Children Hospitalized with Asthma
Authors: Samady Waheeda , Rodriguez Victoria A , Gupta Ruchi , Palac Hannah , Karamanis Marina , Press Valerie G
Published: April 2019

Past studies have not evaluated inhaler use in hospitalized children with asthma. The objectives of this study were to evaluate inhaler technique in hospitalized pediatric patients with asthma and identify risk factors for improper use. We conducted a prospective cross‐sectional study in a tertiary children's hospital for children 2‐16 years of age admitted for an asthma exacerbation, and inhaler technique demonstrations were analyzed. Of 113 participants enrolled, 55% had uncontrolled asthma, and 42% missed a critical step in inhaler technique. More patients missed a critical step when they used a spacer with mouthpiece instead of a spacer with mask (75% [51%‐90%] vs 36% [27%‐46%]) and were older (7.8 [6.7‐8.9] vs 5.8 [5.1‐6.5] years). Patients using the spacer with mouthpiece remained significantly more likely to miss a critical step when adjusting for other clinical covariates (odds ratio 6.95 [1.71‐28.23], P = .007). Hospital‐based education may provide teachable moments to address poor proficiency, especially for older children using a mouthpiece.
RUY DUARTE DE CARVALHO E O PARADOXO DO MODERNO ESTADO-NAÇÃO ANGOLANO
Authors: Rodrigues Fischgold Christian
Published: April 2019

O presente artigo analisa dois textos publicados pelo autor angolano Ruy Duarte de Carvalho nos últimos anos de sua vida: “Tempo de ouvir o ‘outro’ enquanto o “outro” ainda existe, antes que haja só o outro... (2008), e Da Angola Diversa (2009). Esses textos apresentam uma visão da problemática da representação da diversidade e propõem uma cartografia das alteridades contemporâneas inseridas nas estruturas do Estado angolano.
Journal Scan
Authors: Welyczko Nikki
Published: April 2019

Nikki Welyczko, Associate Professor at the Faculty of Health and Life Sciences, De Montfort University, provides a brief overview of recently published nursing and health articles
Mentioning the unmentionable: a stoma care nurse's journey to discussing sexuality comfortably with ostomates
Authors: Bird Andrew
Published: April 2019

Sexuality is a fundamental activity of daily living, affected by a number of external factors, including illness and surgery, such as stoma formation. Ostomates should have an opportunity to discuss sexuality with a stoma care nurse, but it can be a difficult topic to raise, due to social and cultural taboos, as well as misconceptions about health and roles and denial of problems and responsibilities. Engaging in these difficult conversations is an important skill that can be learned and perfected, so long as the need is identified. This journey is illustrated by the author's personal experience. Permission-giving according to the Ex-PLISSIT model makes it easier for patients to open up about sexuality, making it possible to identify and address common sexual problems experienced by ostomates.
Training a new non-medical endoscopist within 7 months: lessons learned
Authors: Ware Dale
Published: April 2019

Background:

The demands on endoscopy services are ever growing, due to the Bowel Cancer Screening Programme and advancements in endoscopic technologies. In order to meet these needs, service providers have looked to non-medical staff as potential endoscopists in a bid to expand workforces and deliver timely endoscopic procedures to patients, as appropriate, within referral guidelines.

Method:

A training plan was developed to train four nurses to become endoscopists. Two nurses would be trained at a time over a period of 7 months. This article outlines the challenges that were faced and overcome in order to successfully train four non-medical endoscopists within the time frame.

Results:

The target of 200 procedures within the 7 months were met for all trainees.

Conclusion:

Organisation and communication with all disciplines involved were key to a successful training programme. Forward planning and advanced booking of lists were vital to ensure regular training lists and good patient attendance.
Ageing gracefully
Authors: Harrison Penny
Published: April 2019

Penny Harrison, Senior Lecturer in Adult Nursing at De Montfort University, Leicester, discusses a new report from the Centre for Ageing Better
Gaining an advantage in an increasingly competitive sector
Authors: DICKONS GILLY
Published: April 2019

In a sector that seems to be growing day by day, it can be difficult for new clinics to get off the ground, or for well-established clinics to hold on to their clients. In this article, Gilly Dickons explores several ways that business owners can assess the competition and assert their own brand
Noninvasive Detection of Bladder Cancer by Shallow-Depth Genome-Wide Bisulfite Sequencing of Urinary Cell-Free DNA for Methylation and Copy Number Profiling
Authors: Cheng Timothy H T , Jiang Peiyong , Teoh Jeremy Y C , Heung Macy M S , Tam Jacqueline C W , Sun Xiao , Lee Wing-Shan , Ni Meng , Chan Ronald C K , Ng Chi-Fai , Chan K C Allen , Chiu Rossa W K , Lo Y M Dennis
Published: April 2019

BACKGROUND

The current diagnosis and monitoring of bladder cancer are heavily reliant on cystoscopy, an invasive and costly procedure. Previous efforts in urine-based detection of bladder cancer focused on targeted approaches that are predicated on the tumor expressing specific aberrations. We aimed to noninvasively detect bladder cancer by the genome-wide assessment of methylomic and copy number aberrations (CNAs). We also investigated the size of tumor cell-free (cf)DNA fragments.

METHODS

Shallow-depth paired-end genome-wide bisulfite sequencing of urinary cfDNA was done for 46 bladder cancer patients and 39 cancer-free controls with hematuria. We assessed (a) proportional contribution from different tissues by methylation deconvolution, (b) global hypomethylation, (c) CNA, and (d) cfDNA size profile.

RESULTS

Methylomic and copy number approaches were synergistically combined to detect bladder cancer with a sensitivity of 93.5% (84.2% for low-grade nonmuscle-invasive disease) and a specificity of 95.8%. The prevalence of methylomic and CNAs reflected disease stage and tumor size. Sampling over multiple time points could assess residual disease and changes in tumor load. Muscle-invasive bladder cancer was associated with a higher proportion of long cfDNA, as well as longer cfDNA fragments originating from genomic regions enriched for tumor DNA.

CONCLUSIONS

Bladder cancer can be detected noninvasively in urinary cfDNA by methylomic and copy number analysis without previous knowledge or assumptions of specific aberrations. Such analysis could be used as a liquid biopsy to aid diagnosis and for potential longitudinal monitoring of tumor load. Further understanding of the differential size and fragmentation of cfDNA could improve the detection of bladder cancer.
Kant, the transcendental designation of I, and the direct reference theory
Authors: Forgione Luca
Published: April 2019

The aim of this paper is to address the semantic issue of the nature of the representation I and of the transcendental designation, i.e., the self-referential apparatus involved in transcendental apperception. The I think, the bare or empty representation I, is the representational vehicle of the concept of transcendental subject; as such, it is a simple representation. The awareness of oneself as thinking is only expressed by the I: the intellectual representation which performs a referential function of the spontaneity of a thinking subject. To begin with, what exactly does Kant mean when he states that I is a simple and empty representation? Secondly, can the features of the representation I and the correlative transcendental designation explain the indexical nature of the I? Thirdly, do the Kantian considerations on indexicality anticipate any of the semantic elements or, if nothing else, the spirit of the direct reference theory?
CONCEITOS DE PÚBLICO E PRIVADO: UM OLHAR SOB A LUZ DE HABERMAS, FREYREE HOLANDA
Authors: Iglesias Tania Conceição
Published: April 2019

O texto aborda o tema público e privado em sua relação com a política. Amparando-se nos estudos clássicos de Habermas, Freyre e Holanda sobre esfera pública, bem como a formação cultural brasileira, toma o processo histórico de construção de tais conceitos com o propósito de compreender as atuais formas de relacionamento entre o campo político e a sociedade. O trabalho ajuda a entender como foi instaurada a lógica do particular sobre o geral que assegura interesses privados nos setores políticos públicos no Brasil.