bluuebunny/crossref_metadata_2025 huggingface dataset:
Single- versus double-injection costoclavicular block: a randomized comparison
Authors: Layera Sebastián , Aliste Julián , Bravo Daniela , Fernández Diego , García Armando , Finlayson Roderick J , Tran De Q
Published: January 2020

Background

The costoclavicular approach targets the brachial plexus in the proximal infraclavicular fossa, where the lateral, medial, and posterior cords are tightly bundled together. This randomized trial compared single- and double-injection ultrasound-guided costoclavicular blocks. We selected onset time as the primary outcome and hypothesized that, compared with its single-injection counterpart, the double-injection technique would result in a swifter onset.

Methods

Ninety patients undergoing upper limb surgery (at or below the elbow joint) were randomly allocated to receive a single- (n=45) or double-injection (n=45) ultrasound-guided costoclavicular block. The local anesthetic agent (35 mL of lidocaine 1%-bupivacaine 0.25%with epinephrine 5 µg/mL and 2 mg of preservative-free dexamethasone) was identical in all subjects. In the single-injection group, the entire volume of local anesthetic was injected between the three cords of the brachial plexus. In the double-injection group, the first half of the volume was administered in this location; the second half was deposited between the medial cord and the subclavian artery. After the performance of the block, a blinded observer recorded the onset time (defined as the time required to achieve a minimal sensorimotor composite score of 14 out of 16 points), success rate (surgical anesthesia) and block-related pain scores. Performance time and the number of needle passes were also recorded during the performance of the block. The total anesthesia-related time was defined as the sum of the performance and onset times.

Results

Compared with its single-injection counterpart, the double-injection technique displayed shorter onset time (16.6 (6.4) vs 23.4 (6.9) min; p<0.001; 95% CI for difference 3.9 to 9.7) and total anesthesia-related time (22.5 (6.7) vs 28.9 (7.6) min; p<0.001). No intergroup differences were found in terms of success and technical execution (ie, performance time/procedural pain). The double-injection group required more needle passes than the single-injection group (2 (1–4) vs 1 (1–3); p<0.001).

Conclusion

Compared with its single-injection counterpart, double-injection costoclavicular block results in shorter onset and total anesthesia-related times. Further investigation is required to determine if a triple-injection technique (with targeted local anesthetic injection around each cord of the brachial plexus) could further decrease the onset time.

Trial registration number

NCT03595514.
Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis
Authors: Smolen Josef S , Choe Jung-Yoon , Weinblatt Michael E , Emery Paul , Keystone Edward , Genovese Mark C , Myung Gihyun , Hong Evelyn , Baek Inyoung , Ghil Jeehoon
Published: January 2020

Objective

To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status.

Methods

Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models.

Results

1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI.

Conclusion

A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity.

Trial registration numbers

NCT01895309,NCT01936181andNCT02167139
Laboratory study on subgrade fluidization under undrained cyclic triaxial loading
Authors: Indraratna Buddhima , Singh Mandeep , Nguyen Thanh Trung , Leroueil Serge , Abeywickrama Aruni , Kelly Richard , Neville Tim
Published: January 2020

A long-term issue that has hampered the efficient operation of heavy-haul tracks is the migration of fluidized fines from the shallow soft subgrade to the overlying ballast, i.e., mud pumping. This paper presents a series of undrained cyclic triaxial tests where realistic cyclic loading conditions were simulated at low confining pressure that is typical of shallow subgrade beneath a ballast track. Subgrade soil specimens with a low-plasticity index collected from a field site with recent history of mud pumping were tested at frequencies from 1.0 to 5.0 Hz and a cyclic stress ratio (CSR) from 0.1 to 1.0. The experimental results indicate that under adverse loading conditions of critical cyclic stress ratio (CSRc) and frequency, there is upward migration of moisture and the finest particles towards the specimen top and this causes the uppermost part of the soil specimen to soften and fluidize. Conversely, a smaller value of CSR tends to maintain stability of the specimen despite the increasing number of loading cycles. It is noteworthy that for any given combination of CSR and frequency, the relative compaction has a significant influence on the cyclic behaviour of the soil and its potential for fluidization.
Responses of Engelmann spruce to inoculation with Leptographium abietinum, a symbiotic fungus of the North American spruce beetle
Authors: Stewart Jane E. , Harris Franklin L. , Otto Kristen , Davis Thomas Seth
Published: January 2020

Symbiotic fungi associated with tree-killing bark beetles can alter host-tree physiology with consequences for tree survival, and symbiont genetic variation and environmental variability may impact these interactions. Here, we test whether multiple genetically distinct isolates of a symbiotic fungus (Leptographium abietinum (Peck) M.J. Wingf.) associated with North American spruce beetle (Dendroctonus rufipennis (Kirby, 1837)) vary in their ability to manifest defensive responses consistent with disease symptoms in seedlings of Engelmann spruce (Picea engelmannii Parry ex Engelm.), a primary host-tree species for the beetle–fungus complex in North America. Our experiments incorporate variation in both host-tree water availability and host defenses (phloem monoterpene concentration). Three central findings emerged: (i) isolates varied considerably in their effects on host trees — inoculation with L. abietinum isolates from Colorado caused significantly larger phloem lesions than isolates from Wyoming, though all isolates caused phloem oxidation; (ii) neither water availability nor spruce phloem monoterpene concentrations impacted lesion formation; and (iii) both inoculation with L. abietinum and water deficit inhibited the formation of callus tissue at wound sites. We conclude that L. abietinum isolates vary in their virulence and that inoculation is not lethal but may benefit beetles by altering tree defensive responses.
Validation and comparison of ammonia measurement techniques used to determine ammonia absorbed by passive absorption samplers
Authors: Kure Jakob Lavrsen , Krabben Jakob , Duelund Lars , Vilms Pedersen Simon , Sommer Sven Gjedde
Published: January 2020

Emission of ammonia from agriculture is a major concern. The analytical analysis of ammonia is known to have some challenges and might be causing systematic errors. The effect of absorbing acids on an ion selective electrode (ISE) and the Berthelot colouring reaction, in terms of precision, was quantified. We show that commonly used acid absorbents do not have a significant influence on the precision of the ISE, whereas the acids had significant influence on measurements using the Berthelot reaction. Using the ISE in low-volume eluates (3 mL) did not influence the precision compared with the recommended 100 mL.
Preparation of Mesoporous/Microporous MnCo2O4 and Nanocubic MnCr2O4 Using a Single Step Solution Combustion Synthesis for Bifunction Oxygen Electrocatalysis
Authors: Ashok Anchu , Kumar Anand , Ponraj Janarthanan , Mansour Said A.
Published: January 2020

We report the synthesis of mesoporous/microporous MnCo2O4 and cubic MnCr2O4 using solution combustion synthesis for oxygen reduction and oxygen evolution reactions. XRD and TEM analysis indicate small crystallites of MnCo2O4 forming ultra-thin layer of irregular structures that lead to porous morphology. A slightly larger crystallite size was observed for MnCr2O4. The surface oxygen defect in MnCo2O4 is much higher than MnCr2O4 that enhances the active sites for the oxygen adsorption and promotes fast dissociation in presence of more exposed Mn/Co sites during the oxygen electrocatalysis. The electrochemical properties of the synthesized catalysts were analysed using CV, LSV, EIS and CA showing high limiting current density and kinetic current density, positive onset and halfwave potential and higher number of overall electron transfer in MnCo2O4 that MnCr2O4. Chronoamperometric (CA) runs for 24 h shows excellent stability of MnCo2O4 without any significant decrease in the current or potential value in ORR and OER. On basis of the activity and stability performance, MnCo2O4 shows to be a promising bifunctional electrocatalyst, with significantly improved performance than previously reported Mn and Co mixed oxides, and comparable to Pt and Ru based catalysts in terms of durability, onset potential and Tafel slope.
Review—Graphene-Based Water Quality Sensors
Authors: Zubiarrain-Laserna Ana , Kruse Peter
Published: January 2020

Water is fundamental to most aspects of human civilization and terrestrial life in general. The problem of deteriorating water quality is very real, but often hard to quantify for lack of data. Hence the development of water quality sensors has become an urgently important area of research. Here we summarize an emerging class of water quality sensors based on field effect or chemiresistive geometries, which work completely in the solid state and can operate without reference electrodes. Such devices are candidates for continuous online monitoring applications of surface, ground, drinking, process, and wastewater streams. Single layer and few layer graphenes are suitable materials for the sensing channels in these devices due to their chemical and mechanical robustness and favorable electronic properties. While single layer graphene devices are more sensitive, few layer graphene sensors are easier to manufacture at a lower cost and offer a wider dynamic range. Detection of pH, disinfectants, mercury, lead, chromium, arsenic, potassium, calcium, some anions, as well as organic and biological species has all been demonstrated at the proof of concept stage, with much more work in progress. One can anticipate the commercial availability of such devices in the near future.
Changes in face and face pareidolia processing in patients with migraine: an ERP study
Authors: Akdeniz Gülsüm , Gumusyayla Sadiye , Vural Gonul , Bektas Hesna , Deniz Orhan
Published: January 2020

Migraine is a multifactorial brain disorder characterized by recurrent disabling headache attacks. One of the possible mechanisms in the pathogenesis of migraine may be a decrease in inhibitory cortical stimuli in the primary visual cortex attributable to cortical hyperexcitability. The aim of this study was to investigate the neural correlates underlying face and face pareidolia processing in terms of the event-related potential (ERP) components, N170, vertex positive potential (VPP), and N250, in patients with migraine. In total, 40 patients with migraine without aura, 23 patients with migraine and aura, and 30 healthy controls were enrolled. We recorded ERPs during the presentation of face and face pareidolia images. N170, VPP, and N250 mean amplitudes and latencies were examined. N170 was significantly greater in patients with migraine with aura than in healthy controls. VPP amplitude was significantly greater in patients with migraine without aura than in healthy controls. The face stimuli evoked significantly earlier VPP responses to faces (168.7 ms, SE = 1.46) than pareidolias (173.4 ms, SE = 1.41) in patients with migraine with aura. We did not find a significant difference between N250 amplitude for face and face pareidolia processing. A significant difference was observed between the groups for pareidolia in terms of N170 [F(2,86) = 14,75, P < 0.001] and VPP [F(2,86) = 16.43, P < 0.001] amplitudes. Early ERPs are a valuable tool to study the neural processing of face processing in patients with migraine to demonstrate visual cortical hyperexcitability.

NEW & NOTEWORTHY Event-related potentials (ERPs) are important for understanding face and face pareidolia processing in patients with migraine. N170, vertex positive potential (VPP), and N250 ERPs were investigated. N170 was revealed as a potential component of cortical excitability for face and face pareidolia processing in patients with migraine.
Indirect pathway control of firing rate and pattern in the substantia nigra pars reticulata
Authors: Simmons DeNard V. , Higgs Matthew H. , Lebby Sharmon , Wilson Charles J.
Published: January 2020

Unitary pallido-nigral synaptic currents were measured using optogenetic stimulation, which activated up to three unitary synaptic inputs to each substantia nigra pars reticulata (SNr) cell. Episodic barrages of synaptic conductances were generated based on in vivo firing patterns of globus pallidus pars externa (GPe) cells and applied to SNr cells using conductance clamp. Barrage inputs were compared to continuous step conductances with the same mean. Barrage inputs and steps both slowed SNr neuron firing and produced disinhibition responses seen in peristimulus histograms. Barrages were less effective than steps at producing inhibition and disinhibition responses. Barrages, but not steps, produced irregular firing during the inhibitory response. Phase models of SNr neurons were constructed from their phase-resetting curves. The phase models reproduced the inhibition and disinhibition responses to the same inputs applied to the neurons. The disinhibition response did not require rebound currents but arose from reset of the cells’ oscillation. The differences in firing rate and irregularity in response to barrage and step inhibition resulted from the high sensitivity of SNr neurons to inhibition at late phases in their intrinsic oscillation. During step inhibition, cells continued rhythmic firing at a reduced rate. During barrages, brief bouts of intense inhibition stalled the cells’ phase evolution late in their cycle, close to firing, and even very brief respites from inhibition rapidly released single action potentials. The SNr cell firing pattern reflected the fine structure of the synaptic barrage from GPe, as well as its onset and offset.

NEW & NOTEWORTHY The pallido-nigral pathway connects the striatum to spontaneously active basal ganglia output neurons in the substantia nigra. Each substantia nigra neuron receives powerful inhibitory synaptic connections from a small group of globus pallidus cells and may fire during pauses in pallidal activity. Despite lacking any hyperpolarization-activated rebound currents, they fire quickly to even brief pauses in the pallido-nigral inhibition. The mechanism of their rapid disinhibitory response is explained by features of their phase-resetting curves.
Connexins: Key Players in the Control of Vascular Plasticity and Function
Authors: Pohl Ulrich
Published: January 2020

Of the 21 members of the connexin family, 4 (Cx37, Cx40, Cx43, and Cx45) are expressed in the endothelium and/or smooth muscle of intact blood vessels to a variable and dynamically regulated degree. Full-length connexins oligomerize and form channel structures connecting the cytosol of adjacent cells (gap junctions) or the cytosol with the extracellular space (hemichannels). The different connexins vary mainly with regard to length and sequence of their cytosolic COOH-terminal tails. These COOH-terminal parts, which in the case of Cx43 are also translated as independent short isoforms, are involved in various cellular signaling cascades and regulate cell functions. This review focuses on channel-dependent and -independent effects of connexins in vascular cells. Channels play an essential role in coordinating and synchronizing endothelial and smooth muscle activity and in their interplay, in the control of vasomotor actions of blood vessels including endothelial cell reactivity to agonist stimulation, nitric oxide-dependent dilation, and endothelial-derived hyperpolarizing factor-type responses. Further channel-dependent and -independent roles of connexins in blood vessel function range from basic processes of vascular remodeling and angiogenesis to vascular permeability and interactions with leukocytes with the vessel wall. Together, these connexin functions constitute an often underestimated basis for the enormous plasticity of vascular morphology and function enabling the required dynamic adaptation of the vascular system to varying tissue demands.
Defining Highway Node Acceptance Capacity (HNAC): Theoretical Analysis and Data Simulation
Authors: Liu Xingliang , Xu Jinliang , Dong Yaping , Ru Han , Duan Zhihao
Published: January 2020

A new concept of Highway Node Acceptance Capacity (HNAC) is proposed in this paper inspired by a field data observation. To understand HNAC in microscopic view, boundary condition of successful merging is found using car-following behaviours and lane-changing rules, which could also explain traffic oscillations. In macroscopic view, linear positive relationship between HNAC and background traffic volume is obtained based on moving bottleneck. To determine the explicit form of the relationship, data simulation considering car-following behaviours and traffic flow theory is used. In the results, the synchronization phenomenon of oscillation in on-ramp (with respect to main road) and intersected road is found. The explicit equation of HNAC is determined based on standard deviation and correlation coefficient analysis, and also proved to be accurate with model validation, which is helpful in studies related to propagation mechanism of traffic emergencies on highway network.
EMT and Back Again: Visualizing the Dynamic Phenotypes of Metastasis
Authors: Bunz Fred
Published: January 2020

To what extent does the acquisition of mesenchymal phenotypes by tumor epithelial cells contribute to metastasis? A definitive answer to this question has remained elusive despite much experimentation and debate. Recently, an influential study based on fluorescence-based lineage tracing technology provided evidence that very few of the cells that populate experimental metastases in fact undergo the epithelial-to-mesenchymal transition. Persistent questions regarding the concordance between marker conversion and cell phenotypes prompted Lourenco and colleagues to complement their lineage tracking system with single-cell analysis. This granular approach provides an unprecedented view of the phenotypic transitions that take place during metastasis and their striking heterogeneity.

See related article by Lourenco et al., p. 163
PD-1 Blockade Reinvigorates Bone Marrow CD8+ T Cells from Patients with Multiple Myeloma in the Presence of TGFβ Inhibitors
Authors: Kwon Minsuk , Kim Chang Gon , Lee Hoyoung , Cho Hyunsoo , Kim Youngun , Lee Eung Chang , Choi Seong Jin , Park Junsik , Seo In-Ho , Bogen Bjarne , Song Ik-Chan , Jo Deog-Yeon , Kim Jin Seok , Park Su-Hyung , Choi Inhak , Choi Yoon Seok , Shin Eui-Cheol
Published: January 2020

Purpose:

Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma.

Experimental Design:

Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti–PD-1 and TGFβ inhibitors.

Results:

We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1–expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti–PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti–PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFβ, which was overexpressed by myeloma cells.

Conclusions:

Our findings indicate that combined blockade of PD-1 and TGFβ may be useful for the treatment of multiple myeloma.
A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer
Authors: Corn Paul G. , Zhang Miao , Nogueras-Gonzalez Graciela M. , Xiao Lianchun , Zurita Amado J. , Subudhi Sumit K. , Tu Shi-Ming , Aparicio Ana M. , Coarfa Cristian , Rajapakshe Kimal , Huang Shixia , Navone Nora M. , Lin Sue-Hwa , Wang Guocan , Ramachandran Sumankalai , Titus Mark A. , Panaretakis Theocharis , Gallick Gary E. , Efstathiou Eleni , Troncoso Patricia , Logothetis Christopher
Published: January 2020

Purpose:

Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).

Patients and Methods:

Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation.

Results:

Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6–22.7 months), and mOS was not reached. Reductions in PSA ≥ 90%, bone-specific alkaline phosphatase ≥ 50%, and urine N-telopeptides ≥ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1.

Conclusions:

Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
Matrix-Targeting Immunotherapy Controls Tumor Growth and Spread by Switching Macrophage Phenotype
Authors: Deligne Claire , Murdamoothoo Devadarssen , Gammage Anís N. , Gschwandtner Martha , Erne William , Loustau Thomas , Marzeda Anna M. , Carapito Raphael , Paul Nicodème , Velazquez-Quesada Inés , Mazzier Imogen , Sun Zhen , Orend Gertraud , Midwood Kim S.
Published: January 2020

The interplay between cancer cells and immune cells is a key determinant of tumor survival. Here, we uncovered how tumors exploit the immunomodulatory properties of the extracellular matrix to create a microenvironment that enables their escape from immune surveillance. Using orthotopic grafting of mammary tumor cells in immunocompetent mice and autochthonous models of breast cancer, we discovered how tenascin-C, a matrix molecule absent from most healthy adult tissues but expressed at high levels and associated with poor patient prognosis in many solid cancers, controls the immune status of the tumor microenvironment. We found that, although host-derived tenascin-C promoted immunity via recruitment of proinflammatory, antitumoral macrophages, tumor-derived tenascin-C subverted host defense by polarizing tumor-associated macrophages toward a pathogenic, immune-suppressive phenotype. Therapeutic monoclonal antibodies that blocked tenascin-C activation of Toll-like receptor 4 reversed this phenotypic switch in vitro and reduced tumor growth and lung metastasis in vivo, providing enhanced benefit in combination with anti–PD-L1 over either treatment alone. Combined tenascin-C:macrophage gene-expression signatures delineated a significant survival benefit in people with breast cancer. These data revealed a new approach to targeting tumor-specific macrophage polarization that may be effective in controlling the growth and spread of breast tumors.
Clinical Effect of the Acrylonitrile-Co-Methallyl Sulfonate Surface-Treated Membrane as a Cytokine Adsorption Therapy for Sepsis due to Acute Panperitonitis: A Retrospective Cohort Study
Authors: Hayashi Kentarou , Sasabuchi Yusuke , Matsui Hiroki , Nakajima Mikio , Ohbe Hiroyuki , Ono Kazuyuki , Yasunaga Hideo
Published: January 2020

Introduction: Sepsis is a systemic inflammatory response syndrome caused by infectious diseases, with cytokines possibly having an important role in the disease mechanism. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve the outcomes of patients with sepsis through cytokine adsorption. Objective: This study aimed to investigate the clinical effect of the AN69ST membrane in comparison to standard continuous renal replacement therapy (CRRT) membranes for panperitonitis due to lower gastrointestinal perforation. Methods: Using the Diagnosis Procedure Combination database, we identified adult patients with sepsis due to panperitonitis receiving any CRRT. Propensity score matching was used to compare patients who received CRRT with the AN69ST membrane (AN69ST group) and those who received CRRT with other membranes (non-AN69ST group). The primary outcome measure was in-hospital mortality. Results: A total of 528 and 1,445 patients were included in the AN69ST group and in the non-AN69ST group, respectively. Propensity score matching resulted in 521 pairs. There was no significant difference in in-hospital mortality (32.1 vs. 35.5%; p = 0.265) and 30-day mortality (41.3 vs. 42.8%, p = 0.074) between the AN69ST group and the non-AN69ST group. Conclusion: There is no significant difference in-hospital mortality between CRRT with the AN69ST membrane and CRRT with standard CRRT membranes for panperitonitis due to lower gastrointestinal perforation. These results indicate that the AN69ST membrane is not superior to the standard CRRT membrane.
Donepezil Attenuates Obesity-Associated Oxidative Stress and Central Inflammation and Improves Memory Deficit in Mice Fed a High-Fat Diet
Authors: Jiang Luxia , Wang Yingying , Su Lingying , Ren Huimin , Wang Cuiwei , Chen Jianzhong , Fu Xiaobin
Published: January 2020

Background/Aims: Obesity is associated with chronic inflammation and cognitive decline, and is considered a major risk factor for neurodegeneration. Meanwhile, neuroinflammation is important in the pathogenesis and progression of neurodegenerative diseases. Methods:In this study, we tested the hypothesis that donepezil would attenuate central inflammation and oxidative damage and improve memory deficit in high-fat diet (HFD)-fed mice. After 16 weeks on a HFD, C57BL/6J mice were given either donepezil (3 mg/kg, i.p.) or saline for 4 weeks in parallel to a control diet (CD) group. Thereafter, the step-through test was used to assess learning and memory function. Results: In the brain of HFD-fed mice, levels of the proinflammatory cytokines interleukin 16 and tumor necrosis factor α were reduced by donepezil treatment. Similarly, HFD-induced protein levels of advanced glycation end-products and oxidative stress in the brain were significantly decreased by donepezil treatment. Conclusion: Our results indicate that donepezil may reverse obesity-related central inflammation and oxidative damage and improve memory deficit in HFD-fed mice.
Principles of Visualization in Radiation Oncology
Authors: Schlachter Matthias , Preim Bernhard , Bühler Katja , Raidou Renata G.
Published: January 2020

Background: Medical visualization employs elements from computer graphics to create meaningful, interactive visual representations of medical data, and it has become an influential field of research for many advanced applications like radiation oncology, among others. Visual representations employ the user’s cognitive capabilities to support and accelerate diagnostic, planning, and quality assurance workflows based on involved patient data. Summary: This article discusses the basic underlying principles of visualization in the application domain of radiation oncology. The main visualization strategies, such as slice-based representations and surface and volume rendering are presented. Interaction topics, i.e., the combination of visualization and automated analysis methods, are also discussed. Key Messages: Slice-based representations are a common approach in radiation oncology, while volume visualization also has a long-standing history in the field. Perception within both representations can benefit further from advanced approaches, such as image fusion and multivolume or hybrid rendering. While traditional slice-based and volume representations keep evolving, the dimensionality and complexity of medical data are also increasing. To address this, visual analytics strategies are valuable, particularly for cohort or uncertainty visualization. Interactive visual analytics approaches represent a new opportunity to integrate knowledgeable experts and their cognitive abilities in exploratory processes which cannot be conducted by solely automatized methods.
A Case of Complex and Abnormal Behaviors at Night: The Role of the Epilepsy Monitoring Unit in Diagnosis
Authors: Diaz-Abad Montserrat , Sanchez Ana M. , Kabir Arif , Konikkara John
Published: January 2020

Complex nocturnal behaviors associated with sleep have many potential causes, including parasomnias and epilepsy. Although the type of event and description can frequently lead to a diagnosis, sometimes it is challenging clinically to determine the cause of the behaviors, requiring a more in-depth investigation. We report the case of a 29-year-old woman with a long history of complex abnormal behaviors and visual hallucinations at night. An extensive clinical evaluation failed to reveal a definitive cause of these episodes, prompting a 3-day epilepsy monitoring unit admission. During the stay, several events were captured on video electroencephalography, leading to a conclusive final diagnosis. This case highlights the challenging task of finding a definitive diagnosis in cases of complex nocturnal behaviors and the potential role of an admission to an epilepsy monitoring unit to help diagnose the cause of these behaviors.
Re-Evaluating Evidence for Best Practice in Paediatric Speech-Language Pathology
Authors: Dodd Barbara
Published: January 2020

Background: Systematic reviews of treatment trials for children with speech and language difficulties often exemplify the limited clinical usefulness of the evidence base, reflecting recent literature in evidence-based medicine. Other studies report that clinicians often fail to seek information about best practice, across the health professions. Consequently, clinical researchers, including those in speech-language pathology, have sought alternative methodologies for determining best practice. Summary: Some approaches focus on “pragmatic trials,” usually as part of existing health services. Others place case management of individuals at the centre of intervention presenting studies of one or more cases, including N-of-1 randomized controlled trials and cross-over group designs. Clinical case studies can provide important theoretical data contributing to our understanding of the development of typical and atypical communication. Precision medicine (also known as personalized medicine) is an emerging approach to building the clinical evidence base that acknowledges the importance of individual genetic and environmental differences between people. With increasing knowledge of aetiological heterogeneity, even within children presenting with the same diagnosis (e.g., childhood apraxia of speech), data reinforce the edict that children are not all born equal. Key Message: This review argues that to understand response to treatment, it is critical to examine child-related factors as well as the variables of the intervention itself.
Impact of Buprenorphine Dosage on the Occurrence of Relapses in Patients with Opioid Dependence
Authors: Reimer Jens , Vogelmann Tobias , Trümper Daniel , Scherbaum Norbert
Published: January 2020

Objectives: Buprenorphine (BUP) is used in opioid maintenance treatment (OMT) for opioid-dependent patients. Previous real-world evidence suggests that many patients receive lower BUP dosage than recommended, with 38% of patients receiving <6 mg BUP per day. The goal of this research is to evaluate the impact of BUP dosage on the risk of relapses in the real world. Methods: This study was based on German claims data of 4 million patients. Patients identified by International Classification of Diseases, 10th Edition F11.2 (opioid dependence) between 2011 and 2012 and at least one BUP prescription were selected for this study (n = 364) and followed up over 4 years. Patients were assigned to 6 dosage groups, with <6 mg/day serving as low dosage/reference category. The impact of dosage on the occurrence of relapses (indicated by treatment interruption of >3 months without OMT prescription or hospital admissions) was examined using multivariate logistic regression. Age, gender, comorbidities, fixed/variable dosing, and up-dosing were used as covariates. Results: Results showed a protective effect of higher BUP as higher BUP dosages were significantly associated with a lower risk of relapse. Using low dosage (<6 mg/day) as the reference category, ORs were 0.40 (95% CI 0.19–0.87) at 6–<8 mg/day, 0.28 (0.15–0.56) at 8–<10 mg/day, 0.26 (0.10–0.67) at 10–<12 mg/day, 0.40 (0.18–0.92) at 12–<16 mg/day, and 0.18 (0.09–0.37) at ≥16 mg/day. No covariate showed a significant effect on the probability of relapse. Conclusions: The present study used a large German health claims dataset to confirm that higher BUP dosages are a protective factor for avoiding relapses in opioid-dependent patients, thus highlighting the importance of adequate BUP dosing in relapse prevention.
Prädiktive Analytik aus der Perspektive der Klinischen Psychologie und Psychotherapie
Authors: Hilbert Kevin , Lueken Ulrike
Published: January 2020

Während in der somatischen Medizin mittlerweile eine Vielzahl von biologischen Markern für die Diagnostik und Therapieplanung vorliegen, gibt es keine vergleichbaren bio­logischen oder psychologischen Marker für psychische Störungen. Hier sind die Pathogenese und Wirkung psychotherapeutischer Interventionen durch eine Vielzahl mitei­nander interagierender Faktoren determiniert. Die prädiktive Analytik verfügt mit dem maschinellen Lernen über eine aussichtsreiche Methode, komplexe Muster und Interaktionen zwischen verschiedenen Variablen in Aussagen für den individuellen Patienten zu übersetzen. Diese Methoden bestimmen (“lernen”) aus bereits vorhandenen Daten die Beziehung zwischen Prädiktoren und Ergebnissen und können anschließend das entwickelte Modell auf neue Daten, bei denen das Ergebnis noch offen ist, anwenden. Zuvor muss aber zwingend geprüft werden, ob das Gelernte tatsächlich bedeutungsvoll ist. Zur Illustration des Ansatzes stellen wir eine Reihe von Studien vor, die das Paradigma der prädiktiven Analytik für diagnostische Fragestellungen, Vorhersage von Risikoverläufen sowie zur Prognose von Psychotherapieergebnissen genutzt haben. Die Ergebnisse sind vielversprechend; vor einem Einsatz in der klinischen Praxis muss die Vorhersagegenauigkeit jedoch weiter gesteigert und in verschiedenen Settings und Populationen überprüft werden. Zur Verbesserung der Vorhersagegüte scheinen insbesondere die Berücksichtigung unterschiedlicher Datenmodalitäten wie klinische Maße, (f)MRT-Daten und genetische Daten sowie der Fokus auf Variablen, die Mechanismen von Psychopathologie und Veränderungsmechanismen gut abbilden, sinnvoll. Darüber hinaus sollte eine enge Zusammenarbeit mit Vertretern von Praktikern und Betroffenen stattfinden, um die Akzeptanz solcher Marker zu gewährleisten. Wenn dies gelingt, bieten derartige Marker das Potenzial, die Diagnosesicherheit insbesondere in ­schwierigen Fällen deutlich zu erhöhen, mögliche Risikoverläufe früh zu identifizieren und die Zuweisung von Patienten zu den für sie bestmöglichen Behandlungen zu unterstützen.
Interrogation of the Multiple Sclerosis Prodrome Using High-Dimensional Health Data
Authors: Zhao Yinshan , Wijnands José M.A. , Högg Tanja , Kingwell Elaine , Zhu Feng , Evans Charity , Fisk John D. , Marrie Ruth Ann , Tremlett Helen
Published: January 2020

Background: There is growing evidence of a prodromal period in multiple sclerosis (MS). A better understanding of the prodrome may facilitate prompt recognition and treatment of MS as well as narrowing of the etiologically relevant ­period when searching for MS risk factors. Objectives: To explore and further delineate the MS prodrome, we used statistical learning techniques to examine associations of physician-generated diagnostic codes and prescription medication classes in the 5 years before the first demyelinating-related claim for MS cases and matched population controls. Methods: In this matched cohort study, we accessed data from linked health administrative hospital, physician, and prescription databases from British Columbia, Canada, between 1996 and 2013. We focused on 7 medication classes previously identified as associated with the MS prodrome: urinary anti-spasmodics, glucocorticoids, muscle relaxants, anti-epileptics, dopa-derivatives, benzodiazepine, and antivertigo preparations. Diagnostic codes associated with the use of each medication class were first identified using LASSO logistic regression analyses in two-thirds of the cohort and then validated using multivariate logistic regressions in the remaining cohort. Results: Our analyses included 4,862 MS cases and 22,649 controls. Although the identified diagnostic codes showed fair to good predictive performance in 6 medication classes (C-index = 0.712–0.858), these codes failed to fully explain the higher usage of these medications by the MS cases. Compared to controls of the same age, sex, and diagnostic codes, MS cases had higher odds of filling a prescription for antivertigo preparations (adjusted OR [aOR] 2.48; 95% CI 1.92–3.19), anti-epileptics (aOR 2.34; 1.90–2.90), glucocorticoids (aOR 1.76; 1.52–2.03), urinary anti-spasmodics (aOR 1.72; 1.20–2.46), and muscle relaxants (aOR 1.33; 1.13–1.56). Conclusions: We observed markedly higher use of specific medications in MS cases in the 5 years before the first demyelinating claim. The overrepresentation of specific medications in MS cases, which was not fully explained by the physician diagnoses, may represent a signature of the MS prodrome.
Management of Presumed Acute Kidney Injury during Hypertensive Therapy: Stay Calm and Carry on?
Authors: Chen Teresa K. , Parikh Chirag R.
Published: January 2020

Background: Recent studies have demonstrated that intensive blood pressure control is associated with improved cardiovascular outcomes. Acute kidney injury (AKI), however, was more common in the intensive treatment group prompting concern in the nephrology community. Summary: Clinical trials on hypertension control have traditionally defined AKI by changes in serum creatinine. However, serum creatinine has several inherent limitations as a marker of kidney injury, with various factors influencing its production, secretion, and elimination. Urinary biomarkers of kidney injury and repair have the potential to provide insight on the presence and phenotype of kidney injury. In both the Systolic Blood Pressure Intervention Trial and the Action to Control Cardiovascular Risk in Diabetes study, urinary biomarkers have suggested that the increased risk of AKI associated with intensive treatment was due to hemodynamic changes rather than structural kidney injury. As such, clinicians who encounter rises in serum creatinine during intensification of hypertension therapy should “stay calm and carry on.” Alternative explanations for serum creatinine elevation should be considered and addressed if appropriate. When the rise in serum creatinine is limited, particularly if albuminuria is stable or improving, intensive blood pressure control should be continued for its potential long-term benefits. Key Messages: Increases in serum creatinine during intensification of blood pressure control may not necessarily reflect kidney injury. Clinicians should evaluate for other contributing factors before stopping therapy. Urinary biomarkers may address limitations of serum creatinine as a marker of kidney injury.
Uncommon Location of Purpura Fulminans: Case Report and Literature Review
Authors: Alsharif Sahar Hasan , Al-Omair Abdullah , Andijani Fedaa
Published: January 2020

Purpura fulminans is a critical, mostly fatal, thrombotic syndrome that requires urgent intervention. Purpura fulminans is an acute purpuric rash characterized by coagulation of the microvasculature, which leads to purpuric lesions and skin necrosis. In this report, we present a rare case of an adult patient who was admitted with rapidly forming purpura fulminans in an uncommon location.
Erwartungen und Kenntnisse von Ausbildungskandidaten in Verhaltenstherapie zu Psychotherapienebenwirkungen
Authors: Schermuly-Haupt Marie-Luise , Linden Michael
Published: January 2020

Hintergrund: Die Aufklärung, Erkennung, Vorbeugung und Bearbeitung von Psychotherapienebenwirkungen stellt hohe Anforderungen an Therapeuten. Grundsätzlich gilt zudem, dass es psychologische Barrieren gibt, negative therapeutische Entwicklungen wahrzunehmen und dem eigenen therapeutischen Handeln zuzuordnen. Dazu trägt bei, dass dieses Thema bislang in der Ausbildung eher wenig Beachtung findet und kaum systematisch abgehandelt wird. Um den eventuellen Handlungsbedarf abschätzen zu können, sind Daten von Interesse zu den einschlägigen Einstellungen und Kenntnissen von Therapeuten in Ausbildung. Methode: In einem halbstrukturierten Interview wurden 100 Psychotherapeuten in Ausbildung mit dem Schwerpunkt Verhaltenstherapie zu Nebenwirkungen ihrer Arbeit befragt. Die Therapeuten machten Angaben zur Qualität, Häufigkeit und den möglichen Ursachen von Psychotherapienebenwirkungen. Ergebnisse: Therapeuten in Ausbildung rechnen in etwa jedem 2. Fall mit dem Auftreten von Nebenwirkungen. Sie erwarten vor allem Symptomverschlechte­rung und negative Entwicklungen im sozialen Netz. Es zeigt sich eine Tendenz, das eigene Verfahren und die eigenen Behandlungen für weniger riskant zu halten als die der Kollegen. Ursachen von Nebenwirkungen sehen die Therapeuten vor allem in der therapeutischen Beziehung sowie The­rapeutenvariablen und weniger in Patientencharakteristika. Schlussfolgerung: Psychotherapeuten in Ausbildung sind sich dem Problem der Nebenwirkungen durchaus bewusst, was ein guter Ansatzpunkt für die Vermittlung entspre­chender Ausbildungsinhalte ist. An den Aus- und Weiterbildungsinstituten sollten Seminare zum Problem der Psychotherapienebenwirkungen zum Standard gehören.
Age Difference in the Association between Hyponatremia and Infection-Related Mortality in Peritoneal Dialysis Patients
Authors: Qiu Yagui , Ye Hongjian , Wang Yating , Zhong Zhong , Li Hongyu , Huang Fengxian , Yang Xiao , Yu Xueqing , Mao Haiping
Published: January 2020

Objectives: This study aimed to examine the association of serum sodium with infection-related mortality and its age difference among continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: A total of 1,656 CAPD patients from January 2006 to December 2013 were included in this study. All patients were followed up until December 2018. Hyponatremia was defined as serum sodium <135 mmol/L. Cox proportional hazards regression model was used to investigate the relationship between baseline serum sodium levels and infection-related mortality. Results: Participants were aged 47.5 ± 15.3 years, 666 (40.2%) patients were female. Glomerulonephritis was the main cause of end-stage renal disease (61.1%). After a median of 46 months of follow-up, 507 patients died. Among the deaths, 252 (49.7%) died from cardiovascular diseases, 105 (20.7%) from infections, and 150 (29.6%) from other causes. The overall infection-related mortality was 14.8 events per 1,000 patients-year, which was higher in patients aged ≥50 years than those younger than 50 years (28.3 vs. 5.3 events per 1,000 patients-year). In the entire cohort, hyponatremia at was not associated with infection-related (hazards ratios [HR] 1.66, 95% CI 0.91–3.02) and all-cause mortality (HR 1.14, 95% CI 0.83–1.57) after adjusting for potential confounders. There was a significant interaction by age of association of serum sodium with infection-related (p = 0.002) and all-cause (p = 0.0002) death. Age-stratified analysis showed that compared with control group, hyponatremia was independently related to increased risks of infection-related death, but not all-cause mortality in patients aged ≥50 years, with HR of 2.32 (95% CI 1.25–4.32) and 1.33 (95% CI 0.95–1.87), respectively. Conclusions: Hyponatremia was associated with increased risk of infection-related mortality in CAPD patients aged ≥50 years.
APOL1 Genotyping in Potential African American Living Kidney Donors: Utility and Cost-Effectiveness
Authors: Gudsoorkar Prakash , Anand Manish , Abu Jawdeh Bassam G.
Published: January 2020

Background: Apolipoprotein L1 gene (APOL1) variants predispose to nondiabetic kidney disease in African American (AA) patients. Here, we share our experience with APOL1 genotyping of AA potential living kidney donors and offer a perspective on its utility and cost-effectiveness in this population. Methods: Since May 2017, all potential AA living kidney donors at our center underwent APOL1 genotyping early in the donor evaluation process. APOL1 high-risk individuals were declined, whereas those with low-risk genotype continued with further evaluation and testing. Results: One out of 26 potential donors had high-risk genotype and was therefore declined. The rest were eligible to continue the donor evaluation process and 7 of them underwent donor nephrectomy without any complications. A crude cost analysis utilizing our sample suggested probable cost-effectiveness of APOL1 genotyping as it can prevent earlier onset of chronic kidney disease in AA donors. Conclusion: We propose a role for systematically incorporating APOL1 genotyping in the evaluation and informed consent process of potential AA donors while acknowledging the controversial considerations associated with it.