bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic and complement markers in extracellular vesicles in multiple sclerosis
Authors: Bhargava Pavan , Nogueras-Ortiz Carlos , Kim Sol , Delgado-Peraza Francheska , Calabresi Peter A , Kapogiannis Dimitrios 
Published: June 2020

Background: Synaptic loss is a feature of multiple sclerosis pathology that can be seen even in normal-appearing gray matter. Opsonization of synapses with complement components may underlie pathologic synapse loss. Objective: We sought to determine whether circulating neuronal-enriched and astrocytic-enriched extracellular vesicles (NEVs and AEVs) provide biomarkers reflecting complement-mediated synaptic loss in multiple sclerosis. Methods: From plasma of 61 people with multiple sclerosis (46 relapsing–remitting multiple sclerosis (RRMS) and 15 progressive MS) and 31 healthy controls, we immunocaptured L1CAM + NEVs and GLAST + AEVs. We measured pre- and post-synaptic proteins synaptopodin and synaptophysin in NEVs and complement components (C1q, C3, C3b/iC3b, C4, C5, C5a, C9, Factor B, and Factor H) in AEVs, total circulating EVs, and neat plasma. Results: We found lower levels of NEV synaptopodin and synaptophysin in MS compared to controls ( p < 0.0001 for both). In AEVs, we found higher levels of multiple complement cascade components in people with MS compared to controls; these differences were not noted in total EVs or neat plasma. Strikingly, there were strong inverse correlations between NEV synaptic proteins and multiple AEV complement components in MS, but not in controls. Conclusion: Circulating EVs could identify synaptic loss in MS and suggest a link between astrocytic complement production and synaptic loss.
Surrogate endpoints for overall survival in anti-programmed death-1 and anti-programmed death ligand 1 trials of advanced melanoma
Authors: Nie Run-Cong , Yuan Shu-Qiang , Wang Yun , Zou Xue-Bin , Chen Shi , Li Shu-Man , Duan Jin-Ling , Zhou Jie , Chen Guo-Ming , Luo Tian-Qi , Zhou Zhi-Wei , Li Yuan-Fang 
Published: June 2020

Background: We assessed the surrogacy of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) for overall survival (OS) in anti-PD-1/PD-L1 trials of metastatic melanoma through a meta-analysis of randomized controlled trials (RCTs). Methods: PubMed and EMBASE were searched for phase II/III RCTs till June 2019 investigating anti-PD-1/PD-L1 agents. Treatment effect (hazard ratio or odds ratio) on potential surrogates (ORR/DCR/PFS) and OS were collected. At trial level, we assessed the correlation between treatment effect on potential surrogates and OS, weighted by sample size, fixed and random effect models, and calculated the surrogate threshold effect (STE). Sensitivity analyses and leave-one-out cross-validation approach were performed to evaluate the robustness of our findings. Results: We included 8 RCTs (4110 patients; 11 comparisons). We did not identify strong correlations between ORR [coefficient of determination ( R2): 0.09–0.25], DCR (0.41–0.57) and OS. However, we noted a strong correlation between PFS and OS, with R2 of 0.82 in sample size, 0.75 in fixed effect and 0.72 in random effect model weighting, the robustness of which was further verified by leave-one-out cross-validation approach. Sensitivity analyses with restriction to trials with less than 50% crossover, phase III trials, large trials and first-line trials strengthened the correlation (0.78–0.94). The STE for PFS was 0.78. Conclusions: PFS may be the appropriate surrogate for OS in anti-PD-1/PD-L1 trials of metastatic melanoma. A future anti-PD-1/PD-L1 trial would need less than 0.78 for PFS of the upper limit of confidence interval to predict an OS benefit.
Endoscopic Endonasal Approaches to the Medial Intraconal Space: Comparison of Transethmoidal and Prelacrimal Corridors
Authors: Li Lifeng , London Nyall R. , Prevedello Daniel M. , Carrau Ricardo L. 
Published: June 2020

Background Endoscopic transethmoidal and prelacrimal approaches can access the medial intraconal space (MIS). Objective This study aimed to compare advantages and drawbacks of these two approaches, and to explore their appropriate indications for management of lesions at various locations within the MIS. Methods Six injected cadaveric specimens were dissected using an endonasal approach performing a transethmoidal approach on one side and a prelacrimal approach on the contralateral side. The MIS was divided into three Zones: Zone 1 was defined as the area above the superior border of the medial rectus muscle (MRM), Zone 2 as the area between the MRM and the optic nerve, and Zone 3 as the area below the inferior border of MRM. The exposure provided by these two approaches to various Zones within the MIS was assessed and compared. Results The average height of Zone 1 to 3 was 10.35 ± 0.45 mm, 11.07 ± 0.59 mm, and 6.53 ± 0.59 mm, respectively. Both approaches provided adequate exposure of Zone 2 and 3; however, the prelacrimal approach provided direct exposure of the posterosuperior aspect of Zone 2 without retraction of MRM. Retraction of MRM was unavoidable using a transethmoidal approach to enhance further exposure. Access to Zone 1 was adequately achieved through the corridor between superior oblique muscle and MRM via a transethmoidal corridor. Conclusion Conceptualizing the MIS into the three aforementioned Zones seems beneficial to select the optimal approach for lesions restricted to each specific Zone. Both the transethmoidal and prelacrimal approaches provide adequate exposure for select lesions in the MIS.
Prescribing, dosing and titrating exercise in patients with hypertrophic cardiomyopathy for prevention of comorbidities: Ready for prime time
Authors: Cavigli Luna , Olivotto Iacopo , Fattirolli Francesco , Mochi Nicola , Favilli Silvia , Mondillo Sergio , Bonifazi Marco , D’Ascenzi Flavio 
Published: June 2020

Abstract
The beneﬁts of physical activity are well established, leading to both cardiovascular and non-cardiovascular benefits, improving quality of life and reducing mortality. Despite such striking body of evidence, patients with hypertrophic cardiomyopathy are often discouraged by health professionals to practice physical activity and personalised exercise prescription is an exception rather than the rule. As a result, hypertrophic cardiomyopathy patients are on average less active and spend significantly less time at work or recreational physical activity than the general population. Exercise restriction derives from the evidence that vigorous exercise may occasionally trigger life-threatening arrhythmias and sudden cardiac death. However, while participation in competitive sports should be prudentially denied, hypertrophic cardiomyopathy patients can benefit from the positive effects of regular physical activity, aimed to reduce the risk of comorbidities and improve the quality of life. Based on this rationale, exercise should be prescribed and titrated just like a drug in hypertrophic cardiomyopathy patients, considering individual characteristics, symptoms, past medical history, objective individual response to exercise, previous training experience and stage of disease. Type, frequency, duration, and intensity should be defined on a personal basis. Yet exercise prescription in hypertrophic cardiomyopathy and its long-term effects represent major gaps in our current knowledge and require extensive research. We here review existing evidence regarding benefits and hazards of physical activity, with specific focus on viable modalities for tailored and safe exercise prescription in these patients, highlighting future developments and relevant research targets.
Haemodynamics and vasopressor support during prolonged targeted temperature management for 48 hours after out-of-hospital cardiac arrest: a post hoc substudy of a randomised clinical trial
Authors: Grand Johannes , Hassager Christian , Skrifvars Markus B , Tiainen Marjaana , Grejs Anders M , Jeppesen Anni Nørgaard , Duez Christophe Henri Valdemar , Rasmussen Bodil S , Laitio Timo , Nee Jens , Taccone FabioSilvio , Søreide Eldar , Kirkegaard Hans 
Published: June 2020

Abstract

Background
Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients’ haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C.

Methods
Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min).

Results
After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg (P=0.19), heart rate was 57±16 and 55±14 beats/min (P=0.18), vasopressor load was 0.06 (0.03–0.15) versus 0.08 (0.03–0.15) µg/kg/min (P=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure (Pgroup=0.32) or lactate (Pgroup=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2–8) beats/min, Pgroup&lt;0.0001) and vasopressor load was significantly higher in the TTM48 group (Pgroup=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05–2.42) P=0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46–1.29) P=0.33).

Conclusions
In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.
Association of traditional cardiovascular risk factors in adults younger than 55 years with coronary heart disease. Case-control study
Authors: Guerrero-Pinedo Fernando , Ochoa-Zárate Laura , Salazar Camilo J , Carrillo-Gómez Diana Cristina , Paulo Manuel , Flórez-Elvira Liliana Janeth , Velasquez-Noreña Jorge Guillermo 
Published: June 2020

Objectives: The traditional cardiovascular risk factors associated with coronary artery disease in individuals younger than 55 years old was determined in this study. Methods: A retrospective, paired case–control study comprised of patients younger than 55 years old who were admitted to the hospital due to acute coronary syndrome with coronary artery disease from 2011 to 2016. There were two controls per case, paired by age, gender, admission date, and health insurance. Data from patients were collected, such as sociodemographic information, cardiovascular risk factors, and drug therapy information. A conditional logistic regression model was created to evaluate the association between traditional cardiovascular risk factors and coronary artery disease. Results: There were 171 cases and 342 controls included in the study. The median age was 49 years, with a predominance of male gender (80.12%). Nearly 66% of cases had at least one traditional cardiovascular risk factor. The most common risk factors were obesity (57.31%), arterial hypertension (45.62%), and smoking (28.97%). Independent risk factors of coronary artery disease in patients younger than 55 years were arterial hypertension (odds ratio, 2.52; 95% confidence interval, 1.48–4.20; p = 0.001) and smoking (odds ratio, 7.15; 95% confidence interval, 3.19–15.99; p = 0.00). No significant association between diabetes mellitus and coronary heart disease in the global group (odds ratio, 2.04; 95% confidence innterval, 0.91–4.58; p = 0.083) was found. Conclusion: For patients younger than 55 years, with a theoretically lower risk of coronary artery disease due to their age, having one or several traditional risk factors (smoking, arterial hypertension, dyslipidemia, or diabetes mellitus) confers an increased risk of coronary artery disease regardless of age.
Beginning power mobility: An exploration of factors associated with child use of early power mobility devices and parent device preference
Authors: Livingstone Roslyn W , Bone Jeffrey , Field Debra A 
Published: June 2020

Objectives Describe and compare young children’s use of four early power mobility devices and examine associations between child and environmental factors that may influence power mobility use and parent device preference. Design Cross-sectional observational study. Methods Power Mobility Days introduced four devices: Wizzybug, Bugzi, Tiger Cub, and a switch-adapted ride-on toy car in a single 60–90 min, play-based session. Results A convenience sample of 74 children, aged 9–68 months (mean: 32.45, SD: 14.08) with mobility limitations, and their parents participated. Children had a range of motor, postural and communication profiles, with cerebral palsy being the most common condition ( n = 55; 73.33%). Assessment of Learning Powered mobility use phase achieved ranged from 1 to 6; mean: 2.34; median: 2. For children who tried all four devices ( n = 51), Friedman test (χ2: 8.27, p =  0.04) suggests Assessment of Learning Powered mobility use phase differs across devices. Of 73 parents who identified a device preference, 43 (59%) chose Wizzybug. Regression analyses suggest that access method and communication function may influence children’s power mobility use, while age, access and postural support requirements may influence parent device choice. Discussion Parent impressions of an early power mobility device may be influenced by many factors, yet be less influenced by child performance.
Endometriosis-related pelvic pain following laparoscopic surgical treatment
Authors: Harris Amani , McCaughey Tristan , Tsaltas Jim , Davies-Tuck Miranda , Ratner Roni , Najjar Haider , Barel Oshri 
Published: June 2020

Introduction: Endometriosis is a common, often-debilitating disease, affecting women of reproductive age. Pain is a common symptom of the disease and is commonly treated by surgery, medical therapy, or a combination of the two. This study aimed to evaluate the rates of ongoing pain post laparoscopic excision and the risk factors for ongoing pain symptoms. Methods: This retrospective cohort study analyzed the medical records of all patients who underwent laparoscopic surgery for endometriosis in a large tertiary healthcare service in Australia between January 2009 and September 2016. Results were analyzed using SPSS statistics version 11. Results: A total of 972 patients met the inclusion criteria; of these, 398 had follow-up at our hospital network and were included in the final analysis. The median age was 34.5 years, 69.6% were of Caucasian ethnicity, and the median body mass index was 25.9; 70.6% of our patients reported decreased pain after surgery. Patients who suffered from chronic pain were twice as likely to experience ongoing pain, while patients with stage 3–4 endometriosis were found to have 65% reduced odds of pain at follow-up (95% confidence interval = 0.22–0.61, p < 0.001). In univariate analysis of non-Caucasian patients, those who had a specialist endometriosis surgeon perform the surgery had significantly higher incidence of symptom improvement (58% reduced odds of recurrent pain and 40% reduced odds, p < 0.05, accordingly). Conclusion: The prevalence and severity of pain associated with endometriosis mandates a thorough understanding of the effectiveness of current management. Our article highlights the utility of laparoscopic surgery in treating endometriosis-associated pain.
Computed tomography-based diagnosis of occult fragility hip fractures offer shorter waiting times with no inadvertent missed diagnosis
Authors: Law Gin Way , Padki Akshay , Tay Kae Sian , Howe Tet Sen , Koh Joyce Suang Bee , Mak May San , Mohan P Chandra , Chan Lai Peng , Png Meng Ai 
Published: June 2020

Purpose: Surgical delay due to the wait for advanced cross-sectional imaging in occult fragility hip fracture management is not well studied. Our study aims to investigate computed tomography (CT) as an alternative to the gold standard magnetic resonance imaging (MRI) in occult hip fracture workup to decrease surgical delay. Methods: We conducted a retrospective review of all CTs and MRIs performed between 2015 and 2017 for patients with clinically suspected fragility hip fractures and negative plain radiographs to investigate surgical delay resulting from the wait for advanced imaging and representations due to missed fractures. Results: A total of 243 scans (42 CTs and 201 MRIs) were performed for occult hip fracture workup over the study timeframe, of which 49 patients (20%) had occult hip fractures [CT: 6 (14%), MRI: 43 (21%), p = 0.296)]. There were no readmissions for fracture in the 12 months following a negative scan. The CT group had shorter waiting times (CT: 29 ± 24 h, MRI: 44 ± 32 h, p = 0.004) without significantly reducing surgical delay (CT: 82 ± 36 h, MRI: 128 ± 58 h, p = 0.196). The MRI group had a higher number of patients with a cancer history ( p = 0.036), reflective of the practice for workup of possible metastases as a secondary intention. Conclusion: Advanced cross-sectional imaging wait times in occult hip fracture workup contribute significantly to surgical delay. Modern CT techniques are not inferior to MRI in detecting occult fractures and may be a suitable alternative in the absence of a cancer history if MRI cannot be obtained in a timely fashion or is contraindicated. Clinicians should utilize the more readily available imaging modality to reduce surgical delay.
Long-Term Outcomes in Macular Telangiectasia Type 2 With Subretinal Neovascularization
Authors: Bottini Alexander R. , Blackorby Barton L. , Michaels Madelyn , Burkett Katherine , Dang Sabin , Blinder Kevin J. , Shah Gaurav K. 
Published: June 2020

Purpose: This work reports long-term outcomes in macular telangiectasia type 2 (MacTel) with subretinal neovascularization (SRNV). Methods: A retrospective, single-center review of medical records was performed on all patients with a diagnosis of MacTel presenting between May 2004 and October 2019. Medical and ocular history, best-corrected visual acuity (BCVA) at baseline and final visit, optical coherence tomography data, and treatment history of SRNV secondary to MacTel were recorded. Results: A total of 471 eyes were diagnosed with MacTel. SRNV was present in 44 eyes (9.3%), of which 38 eyes met inclusion criteria for SRNV. Average follow-up duration in the SRNV group was 78.4 months. All SRNV patients underwent antivascular endothelial growth factor (anti-VEGF) therapy. There was no significant change from mean baseline (0.59 ± 0.45) to final (0.70 ± 0.49) BCVA in the SRNV group as a whole ( P = .13). Subgroup analysis revealed 17 of 38 eyes had SRNV at diagnosis and received immediate anti-VEGF treatment. In this subgroup mean pretreatment BCVA was 0.89 ± 0.43 and the mean final BCVA was 0.87 ± 0.61 ( P = .84). The remainder (21 of 38 eyes) developed SRNV during follow-up. In this subgroup, final BCVA after initiation of treatment was 0.56 ± 0.32, an improvement in BCVA from SRNV onset ( P = .04) and a decrease from pre-SRNV onset baseline BCVA ( P = .008). Conclusions: Visual acuity is maintained, not improved, in long-term follow-up of MacTel with SRNV treated with anti-VEGF. Patients presenting with SRNV have a worse prognosis than those who develop SRNV during follow-up.
Reorganising the emergency department to manage the COVID-19 outbreak
Authors: Quah Li Juan Joy , Tan Boon Kiat Kenneth , Fua Tzay-Ping , Wee Choon Peng Jeremy , Lim Chin Siah , Nadarajan Gayathri , Zakaria Nur Diana , Chan Shi-En Joanna , Wan Paul Weng , Teo Lin Tess , Chua Ying Ying , Wong Evelyn , Venkataraman Anantharaman 
Published: June 2020

Abstract
Background
The COVID-19 disease outbreak that first surfaced in Wuhan, China, in December 2019, has taken the world by storm and ravaged almost every country in the world. Emergency departments (ED) in hospitals are on the frontlines, serving an essential function in identifying these patients, isolating them early whilst providing urgent medical care. This outbreak has reinforced the role of Emergency Medicine in public health. This paper documents the challenges faced and measures taken by a tertiary hospital’s ED in Singapore, in response to the outbreak.

Main body
The ED detected the first case of COVID-19 in Singapore on 22 January 2020 in a Chinese tourist and also the first case of locally transmitted COVID-19 on 3 February 2020. The patient journeys through the patient reception area in the ED and undergoes fever screening before being shunted to isolation areas within the ED. Management and disposition of suspect COVID-19 patients are guided by a close-knit collaboration between ED and department of infectious diseases. With increasing number of patients, back-up plans for expansion of space and staff augmentation have been enacted. Staff safety is also of utmost importance, with provision and guidelines for personal protective equipment and team segregation to ensure no cross-contamination across staff. These have been made possible with an early setup of an operational command and control structure within the ED, managing manpower, logistics, operations, communication and information management and liaison with other clinical departments.

Conclusion
With the large numbers of undifferentiated patients managed by the ED to date, more than 820 patients with COVID-19 have been identified in the hospital. Not a single member of the staff of the SGH Emergency Department has come down with the illness. The various measures undertaken by the department have helped to ensure good staff morale and strict adherence to safety procedures. We share the lessons learnt so that others who manage EDs around the world can benefit from our experience.