bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key aspects of PCSK9 inhibition beyond LDL lowering
Authors: Ramin-Mangata Stéphane , Blanchard Valentin , Lambert Gilles 
Published: September 2018

Purpose of review
Our primary objective is to review the most recent findings on the biology of PCSK9 and on two key aspects of PCSK9 inhibition beyond LDL control of great clinical relevance: the regulation of lipoprotein (a) circulating levels by PCSK9 inhibitors and the putative diabetogenic effects of these novel therapies.

Recent findings
The reality of two distinct extracellular and intracellular pathways by which PCSK9 decreases the abundance of the LDLR at the surface of many cell types, most importantly hepatocytes, has recently been established. In contrast, the exact mechanisms by which PCSK9 inhibitors lower the circulating levels of lipoprotein (a) remain a point of major dispute. Despite strong indications from genetic studies that PCSK9 inhibition should increase diabetes risk, no such effect has been observed in clinical trials, and in-vitro and in-vivo studies do not clarify this issue.

Summary
The trafficking pathways by which PCSK9 enhance LDLR degradation via the endolysosomal extracellular route or via the Golgi–lysosomal intracellular route remain to be fully elucidated. The mechanisms by which PCSK9 inhibitors reduce lipoprotein (a) also merit additional research efforts. The role of PCSK9 on glucose metabolism should likewise be studied in depth.
Pancreatic Cancer–Associated Depression
Authors: Barnes Adam F. , Yeo Theresa P. , Leiby Benjamin , Kay Abigail , Winter Jordan M. 
Published: September 2018

Abstract
The prevalence of major depressive disorder (MDD) in pancreatic cancer (PC) has been reported up to 7 times higher than the general population. Despite repeated studies that show worse quality of life, survival outcomes, and treatment compliance in cancer patients with depression, baseline antidepressant use ranges from 15% to 27%. A meta-analysis of 6 prospective trials specific to PC estimates that 43% of patients with PC experience depression after diagnosis. This is especially alarming in patients with PC, who may experience a prodrome of symptoms including depression and loss of drive. In fact, this prodrome of symptoms may very well be due to an overexpression of indoleamine 2,3-dioxgenase, an enzyme in the kynurenine pathway that leads to serotonin depletion and the buildup of cytotoxic metabolites in the brain. In this literature review, we outline all previous studies pertinent to PC and depression, as well as the molecular underpinnings that may contribute to states of depression, and report on previous randomized control trials in cancer populations that investigate the use of antidepressants to treat depressive symptoms and improve quality of life both prophylactically and after the onset of major depressive disorder. In addition, we detail a case report outlining the precipitous decline in health in 1 patient with PC and depression.
Using the Logic Model Framework to Standardize Quality and Rigor in the DNP Project
Authors: Sun Grace H. , Cherry Barbara 
Published: September 2018

Background
Since the implementation of the DNP degree, there has been controversy, confusion, and inconsistency about the DNP project. To this day, the profession lacks a consensus of what the DNP project should be.

Problem
Despite much in the literature regarding these issues, there is no systematic approach to the development of DNP project guidelines. Consequently, there is now an escalating interest in increasing the quality and rigor of DNP projects.

Approach
Many issues related to the DNP project can be addressed using a logic model approach and incorporating current best practices.

Conclusions
This article demonstrates how a logic model can be used for the development or improvement of DNP project processes, incorporating best practices and evaluation methods to ensure quality and rigor.
Experience of Robotic Exoskeleton Use at Four Spinal Cord Injury Model Systems Centers
Authors: Heinemann Allen W. , Jayaraman Arun , Mummidisetty Chaithanya K. , Spraggins Jamal , Pinto Daniel , Charlifue Susan , Tefertiller Candy , Taylor Heather B. , Chang Shuo-Hsiu , Stampas Argyrios , Furbish Catherine L. , Field-Fote Edelle C. 
Published: September 2018

Background and Purpose:
Refinement of robotic exoskeletons for overground walking is progressing rapidly. We describe clinicians' experiences, evaluations, and training strategies using robotic exoskeletons in spinal cord injury rehabilitation and wellness settings and describe clinicians' perceptions of exoskeleton benefits and risks and developments that would enhance utility.

Methods:
We convened focus groups at 4 spinal cord injury model system centers. A court reporter took verbatim notes and provided a transcript. Research staff used a thematic coding approach to summarize discussions.

Results:
Thirty clinicians participated in focus groups. They reported using exoskeletons primarily in outpatient and wellness settings; 1 center used exoskeletons during inpatient rehabilitation. A typical episode of outpatient exoskeleton therapy comprises 20 to 30 sessions and at least 2 staff members are involved in each session. Treatment focuses on standing, stepping, and gait training; therapists measure progress with standardized assessments. Beyond improved gait, participants attributed physiological, psychological, and social benefits to exoskeleton use. Potential risks included falls, skin irritation, and disappointed expectations. Participants identified enhancements that would be of value including greater durability and adjustability, lighter weight, 1-hand controls, ability to navigate stairs and uneven surfaces, and ability to balance without upper extremity support.

Discussion and Conclusions:
Each spinal cord injury model system center had shared and distinct practices in terms of how it integrates robotic exoskeletons into physical therapy services. There is currently little evidence to guide integration of exoskeletons into rehabilitation therapy services and a pressing need to generate evidence to guide practice and to inform patients' expectations as more devices enter the market.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A231).
Effects of a Gaming Platform on Balance Training for Children With Cerebral Palsy
Authors: Hsieh Hsieh-Chun 
Published: September 2018

Purpose:
A platform requiring multidimensional trunk movement facilitated postural balance in children with cerebral palsy.

Methods:
The intervention group (n = 20) received 12 weeks of playing personal computer (PC) games using the platform, and the control group (n = 20) played the same games using a computer mouse. Outcomes were center–of-pressure sway, the Berg Balance Scale (BBS), Fullerton Advanced Balance Scale (FAB), and Timed Up and Go (TUG) test scores.

Results:
There were significant interactions between groups and time. There was a significant between-group difference in center-of-pressure sway excursion, BBS test, and TUG test over time. Participants in the intervention group had better balance performance compared with the control group.

Conclusion:
Balance training using a PC gaming platform may improve exercise compliance and enhance recovery of balance in children with cerebral palsy.
Physical Therapist Coaching to Improve Physical Activity in Children With Brain Tumors: A Pilot Study
Authors: Ovans Jessica A. , Hooke Mary C. , Bendel Anne E. , Tanner Lynn R. 
Published: September 2018

Purpose:
Children with brain tumors (BTs) experience fatigue and decreased quality of life (QOL). Physical activity (PA) is recommended during and after cancer treatment. We explored whether a fitness tracker intervention combined with tailored coaching by a physical therapist (PT) increased PA and QOL and decreased fatigue in children with BTs.

Methods:
Participants were 7 to 18 years' old, within 2 years of diagnosis, and received a 12-week PA intervention using a fitness tracker combined with 5 PT coaching sessions. Steps/day measured by Fitbit and self-reports of QOL, fatigue, and PA were evaluated at baseline, 12 weeks, and 24 weeks.

Results:
Participants had nonsignificant increase in steps/day. Total fatigue, general, and sleep/rest subscales improved while cognitive fatigue and QOL remained unchanged. Higher steps/day were associated with lower fatigue.

Conclusion:
This is a feasible intervention that may contribute to an increase in PA and improve fatigue in children with BTs.
Adapted Motivational Interviewing to Promote Exercise in Adolescents With Congenital Heart Disease: A Pilot Trial
Authors: McKillop Adam , Grace Sherry L. , Ghisi Gabriela Lima de Melo , Allison Kenneth R. , Banks Laura , Kovacs Adrienne H. , Schneiderman Jane E. , McCrindle Brian W. 
Published: September 2018

Purpose:
To assess a motivational interviewing (MI) intervention to improve moderate-to-vigorous physical activity (MVPA) in adolescents with congenital heart disease.

Methods:
Intervention participants received one-on-one telephone-based adapted MI sessions over 3 months. Outcomes were acceptability, change mechanisms (stage of change and self-efficacy), and limited efficacy (physical activity, fitness, and quality of life).

Results:
Thirty-six participants were randomized. Intervention participants completed 4.2 ± 1.2/6 MI sessions, with no improvements in the high self-efficacy or stage of change observed. Participants accumulated 47.24 ± 16.36 minutes of MVPA/day, and had comparable outcomes to peers without heart disease (except for functional capacity). There was no significant difference in change in any outcome by group.

Conclusions:
The intervention was acceptable, but effectiveness could not be determined due to the nature and size of sample.

Clinical Relevance:
Pediatric cardiac rehabilitation remains the sole effective intervention to increase MVPA in this population.
Transcranial Direct-Current Stimulation on Motor Function in Pediatric Cerebral Palsy: A Systematic Review
Authors: Hamilton Angela , Wakely Luke , Marquez Jodie 
Published: September 2018

Purpose:
To determine effects of transcranial direct-current stimulation (tDCS) on motor function for children with cerebral palsy.

Methods:
Six electronic databases were searched using terms related to tDCS, combined with functional deficits/associated clinical measures. Results were filtered, including randomized controlled trials in English and children with cerebral palsy. Data were extracted using standardized procedures, and the PEDro scale was used to assess quality and meta-analyses conducted.

Results:
From 135 articles, 9 studies with moderate quality met inclusion criteria. Six were included in 7 separate meta-analyses supporting a benefit of tDCS for static balance, only at follow-up. Benefits of tDCS on dynamic balance, step length, and mobility were not established.

Conclusions:
The findings from meta-analyses suggest that tDCS may provide improvements in static balance at follow-up in children with cerebral palsy and positive effects on gait velocity; however, there was heterogeneity. Further research is needed before this therapy can be endorsed.
Evaluation of an AI-Based Detection Software for Acute Findings in Abdominal Computed Tomography Scans
Authors: Winkel David J. , Heye Tobias , Weikert Thomas J. , Boll Daniel T. , Stieltjes Bram 
Published: September 2018

Objective
The aim of this study was to test the diagnostic performance of a deep learning-based triage system for the detection of acute findings in abdominal computed tomography (CT) examinations.

Materials and Methods
Using a RIS/PACS (Radiology Information System/Picture Archiving and Communication System) search engine, we obtained 100 consecutive abdominal CTs with at least one of the following findings: free-gas, free-fluid, or fat-stranding and 100 control cases with absence of these findings. The CT data were analyzed using a convolutional neural network algorithm previously trained for detection of these findings on an independent sample. The validation of the results was performed on a Web-based feedback system by a radiologist with 1 year of experience in abdominal imaging without prior knowledge of image findings through both visual confirmation and comparison with the clinically approved, written report as the standard of reference. All cases were included in the final analysis, except those in which the whole dataset could not be processed by the detection software. Measures of diagnostic accuracy were then calculated.

Results
A total of 194 cases were included in the analysis, 6 excluded because of technical problems during the extraction of the DICOM datasets from the local PACS. Overall, the algorithm achieved a 93% sensitivity (91/98, 7 false-negative) and 97% specificity (93/96, 3 false-positive) in the detection of acute abdominal findings. Intra-abdominal free gas was detected with a 92% sensitivity (54/59) and 93% specificity (39/42), free fluid with a 85% sensitivity (68/80) and 95% specificity (20/21), and fat stranding with a 81% sensitivity (42/50) and 98% specificity (48/49). False-positive results were due to streak artifacts, partial volume effects, and a misidentification of a diverticulum (each n = 1).

Conclusions
The algorithm's autonomous detection of acute pathological abdominal findings demonstrated a high diagnostic performance, enabling guidance of the radiology workflow toward prioritization of abdominal CT examinations with acute conditions.
SUV Harmonization Between Different Hybrid PET/CT Systems
Authors: Rubello Domenico , Colletti Patrick M. 
Published: September 2018

Aim
Current PET/CT lutetium oxyorthosilicate (LSO) or lutetium-yttrium oxyorthosilicate crystal scanners are equipped with sophisticated softwares including point-spread function (PSF) and time-of-flight (TOF) image reconstruction. These softwares are associated with increased SUVs compared with 3D-OSEM reconstructions associated with older BGO PET/CT scanners. The European Association of Nuclear Medicine (EANM) identified the problem of SUV harmonization since 2010 through the EANM Research Ltd European Association of Nuclear Medicine Research Ltd [EARL] FDG PET/CT accreditation program. This required processing 2 reconstructions, one optimized for maximum spatial lesion detection and one for harmonized quantitation. We investigated an alternative single reconstruction method for both qualitative and quantitative analysis optimized to maximize spatial lesion detectability, followed by an intrinsic postreconstruction algorithm for SUV harmonization.

Methods
Phantom and “in vivo” patient data analysis were acquired and analyzed on (a) a Siemens Biograph mCT system with LSO crystals and PSF and TOF algorithms, and on (b) a General Electric Discovery STE system with BGO crystals, without PSF and TOF. A dedicated algorithm (EQ.filter) was tested to harmonize SUV between the 2 scanners compared with EANM/EARL specifications. NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small fillable spheres (lesion to background ratios of 8:1 and 4:1) were used. Phantom data were validated on 7 oncologic patients with 39 hyperactive lesions ranging from 3 mm to 26 mm.

Results
The main benefit of PSF + TOF LSO PET/CT systems was increased contrast for small active lesions. Recovery coefficients measured according to NEMA standards exceeded those obtained by 3D-OSEM reconstruction. SUVmax discrepancies between the 2 PET/CT systems were as high as 149%, dropping to below 10% when optimized by EQ.filter.

Conclusions
A single reconstruction optimized by EQ.filter for maximum spatial lesion detectability is an easy and precise solution to harmonize SUVs between different PET/CT scanners, avoiding a second reconstruction with an additional smoothing filter as requested by EANM/EARL.
Long-term Quality of Life and Gastrointestinal Functional Outcomes After Pancreaticoduodenectomy
Authors: Allen Casey J. , Yakoub Danny , Macedo Francisco Igor , Dosch Austin R. , Brosch Jessica , Dudeja Vikas , Ayala Ronda , Merchant Nipun B. 
Published: September 2018

Objective:
To perform a comprehensive assessment of long-term quality of life (QOL) and gastrointestinal (GI) function in patients following pancreaticoduodenectomy (PD).

Summary of Background Data:
Survival after PD has greatly improved and thus has resulted in a larger population of survivors, yet long-term QOL and GI function after PD is largely unknown.

Methods:
Patients were identified from a global online support group. QOL was measured using the Short Form-36, while GI function was assessed using the Gastrointestinal Symptom Rating Scale. QOL and GI function were analyzed across subgroups based on time after PD. QOL was compared with preoperative measurements and with established values of a general healthy population (GHP). Multivariate linear regression was used to identify predictors of QOL.

Results:
Of the 7605 members of the online support group, 1102 responded to the questionnaire with 927 responders meeting inclusion criteria. Seven hundred seventeen (77.3%) of these responders underwent PD for malignancy. Mean age was 57 ± 12 years and 327 (35%) were male. At the time of survey, patients were 2.0 (0.7, 4.3) years out from surgery, with a maximum 30.7-year response following PD. Emotional and physical domains of QOL improved with time and surpassed preoperative levels between 6 months and 1 year after PD (both P < 0.001). Each GI symptom worsened over time (all P < 0.001). Independent predictors of general QOL in long-term survivors (> 5 years) included total GSRS score [β = −1.70 (−1.91, −1.50)], female sex [β = 3.58 (0.67, 6.46)], and being a cancer survivor [β = 3.93 (0.60, 7.25)].

Conclusions:
Long-term QOL following PD improves over time, however never approaches that of a GHP. GI dysfunction persists in long-term survivors and is an independent predictor of poor QOL. Long-term physical, psychosocial, and GI functional support after PD is encouraged.
Long-term Immunosuppression Adherence After Kidney Transplant and Relationship to Allograft Histology
Authors: Lorenz Elizabeth C. , Smith Byron H. , Cosio Fernando G. , Schinstock Carrie A. , Shah Nilay D. , Groehler Paul N. , Verdick Jayson S. , Park Walter D. , Stegall Mark D. 
Published: September 2018

Background
Nonadherence to immunosuppression after kidney transplant is an important contributor to graft failure. Little is known about how nonadherence changes 3 years posttransplant when Medicare coverage of immunosuppression ends and how that nonadherence impacts allograft histology. The goal of this study was to compare rates of nonadherence during posttransplant years 1 to 3 to years 3 to 5 and examine the relationship between nonadherence during years 3 to 5 and 5-year allograft histology.

Methods
We retrospectively analyzed 552 conventional kidney allografts in patients transplanted at our center between January 1, 1999, and June 1, 2010, who used the Mayo Clinic Specialty Pharmacy for the first 5 years posttransplant. Nonadherence was defined as less than 80% proportion of days covered. Overall adherence to immunosuppression appeared to be higher during years 3 and 5 compared to between years 1 and 3 (89.4% vs 82.9%, respectively; P < 0.0001 [paired t test]).

Results
Overall nonadherence during posttransplant years 3 to 5 appeared to be associated with fibrosis and inflammation on 5-year allograft biopsy but not with transplant glomerulopathy (16.9% vs 5.9%, P = 0.004; 10.4% vs 8.5%, P = 0.61, respectively). After adjusting for nonadherence to calcineurin inhibitor and prednisone therapy, only nonadherence to antimetabolite therapy remained significantly associated with 5-year fibrosis and inflammation (odds ratio, 10.6; 95% confidence interval, 1.5-76.1; P = 0.02).

Conclusions
Efforts to improve long-term adherence, possibly through the use of specialty pharmacies and increased adherence to antimetabolite therapy, may improve long-term allograft histology and survival, although further studies are needed to confirm these findings.
Renal Function, Albuminuria, and the Risk of Cardiovascular Events After Kidney Transplantation
Authors: Lam Ngan N. , Klarenbach Scott , Quinn Robert R. , Hemmelgarn Brenda , Tonelli Marcello , Ye Feng , Ravani Pietro , Bello Aminu K. , Brennan Daniel C. , Lentine Krista L. 
Published: September 2018

Background
The risk of mortality and graft loss is higher in kidney transplant recipients with reduced estimated glomerular filtration rate (eGFR) and albuminuria. It is unclear whether these markers are also associated with cardiovascular events.

Methods
We examined linked healthcare databases in Alberta, Canada to identify kidney transplant recipients between 2002 and 2013 who had at least 1 outpatient serum creatinine and albuminuria measurement at 1-year posttransplant. We determined the relationship between categories of eGFR and albuminuria and the risk of subsequent cardiovascular events.

Results
Among 1069 eligible kidney transplant recipients, the median age was 52 years, 37% were female, and 52% had eGFR ≥60 mL/min per 1.73 m2. Over a median follow-up of 6 years, the adjusted rate of all-cause mortality and cardiovascular events was 2.7-fold higher for recipients with eGFR 15-29 mL/min per 1.73 m2 and heavy albuminuria compared to recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria (rate ratio, 2.7; 95% confidence interval, 1.3-5.7). Similarly, recipients with heavy albuminuria had a threefold increased risk of all-cause mortality and heart failure compared with recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria.

Conclusions
These findings suggest that eGFR and albuminuria should be used together to determine the risk of cardiovascular outcomes in transplant recipients.
Hypothermic Oxygenated Machine Perfusion of the Human Donor Pancreas
Authors: Leemkuil Marjolein , Lier Grietje , Engelse Marten A. , Ploeg Rutger J. , de Koning Eelco J. P. , ‘t Hart Nils A. , Krikke Christina , Leuvenink Henri G. D. 
Published: September 2018

Background
Transplantation of beta cells by pancreas or islet transplantation is the treatment of choice for a selected group of patients suffering from type 1 diabetes mellitus. Pancreata are frequently not accepted for transplantation, because of the relatively high vulnerability of these organs to ischemic injury. In this study, we evaluated the effects of hypothermic machine perfusion (HMP) on the quality of human pancreas grafts.

Methods
Five pancreata derived from donation after circulatory death (DCD) and 5 from donation after brain death (DBD) donors were preserved by oxygenated HMP. Hypothermic machine perfusion was performed for 6 hours at 25 mm Hg by separate perfusion of the mesenteric superior artery and the splenic artery. Results were compared with those of 10 pancreata preserved by static cold storage.

Results
During HMP, homogeneous perfusion of the pancreas could be achieved. Adenosine 5′-triphosphate concentration increased 6,8-fold in DCD and 2,6-fold in DBD pancreata. No signs of cellular injury, edema or formation of reactive oxygen species were observed. Islets of Langerhans with good viability and in vitro function could be isolated after HMP.

Conclusions
Oxygenated HMP is a feasible and safe preservation method for the human pancreas that increases tissue viability.