bluuebunny/crossref_metadata_2025 huggingface dataset:
Case 17.1
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

20-year-old man with abdominal pain and possible Crohn disease

Sagittal image from 3-plane SSFSE scout series (Figure 17.1.1) demonstrates diffuse signal loss over the anterior abdomen and pelvis in comparison to the spine and paraspinous muscle. Axial SSFP images from the mid abdomen (...
Case 17.7
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

59-year-old woman with chronic hepatitis B infection and cirrhosis

Axial fat-suppressed 2D SSFP images acquired on a 3-T system (Figure 17.7.1) demonstrate a cirrhotic liver, splenomegaly, and periumbilical varices. Note also the prominent banding artifact crossing the liver on both images. Similar fat-suppressed 2D SSFP images obtained during the previous examination with a 1.5-T system (...
Case 17.8
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

57-year-old woman with an adnexal mass seen on pelvic US

Coronal FSE T2-weighted images (Figure 17.8.1) reveal abnormal signal superimposing the interior of the pelvis. A second set of coronal FSE images (Figure 17.8.2) demonstrates improved visualization of the pelvis but with persistent linear artifacts. Bright signal from subcutaneous fat superimposes the anterior and posterior margins of sagittal FSE images (...
Case 17.11
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

62-year-old woman with possible pancreatic intraductal papillary mucinous neoplasm

Superiormost image from a venous phase postgadolinium 3D SPGR acquisition (Figure 17.11.1) shows artifact superimposing the lower thorax as well as a possible enhancing lesion in a lower thoracic vertebral body. The inferiormost image is relatively artifact-free (...
Case 17.14
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

65-year-old woman with endometrial carcinoma

Sagittal FSE T2-weighted image (Figure 17.14.1) demonstrates prominent phase ghosting artifacts superimposing the uterus. The series was repeated with an anterior saturation band (Figure 17.14.2) (notice the low signal intensity of the subcutaneous fat) with significant reduction in artifact. The series was repeated again with the phase and frequency directions swapped (ie, the phase encoding direction is now superior-inferior) (...
Case 17.17
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

58-year-old woman with cirrhosis

Axial precontrast (Figure 17.17.1) and arterial phase (Figure 17.17.2) and portal venous phase (Figure 17.17.3) postgadolinium water and fat images from a 3D SPGR Dixon acquisition. Notice that the phase and frequency directions have been swapped on the arterial phase acquisition and that there is a large geographic signal void in the middle of the liver on the water image, with the missing anatomy appearing on the corresponding fat image. All artifacts have been corrected on the portal venous phase images....
Case 17.18
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

39-year-old woman with Crohn disease and suspected primary sclerosing cholangitis

Consecutive IP images from a 2D SPGR IP-OP acquisition (Figure 17.18.1) demonstrate high signal intensity within the IVC and hepatic veins on the superior 2 images which disappears on the bottom images. Note the appearance of high signal intensity within the aorta and celiac artery on the inferior images....
Case 17.21
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

23-year-old man with ulcerative colitis and elevated liver function test results

MIP images from 3D FRFSE MRCP (Figure 17.21.1) demonstrate focal stricture of the common bile duct at its bifurcation in the hepatic hilum. Focal beading of a mildly prominent duct in the left hepatic lobe is also noted. Axial fat-suppressed 2D SSFP images (...
Case 17.24
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

64-year-old woman with pancreatic cancer and suspected hepatic metastases

VR image from 3D MRCP (Figure 17.24.1) demonstrates moderate dilatation of intrahepatic ducts and marked extrahepatic biliary dilatation extending to the pancreatic head, where there is also obstruction of the pancreatic duct. Axial hepatobiliary phase 3D SPGR images obtained 20 minutes following gadoxetate disodium (Eovist) injection (...
Case 17.30
Authors: Lee Christine U. , Glockner James F.
Published: December 2018

19-year-old woman with inflammatory bowel disease and suspected perianal fistula

Axial postgadolinium 2D SPGR image (Figure 17.30.1) demonstrates a prominent artifact extending across the right side of the pelvis along the phase encoding direction.

Zipper artifact

Zipper artifacts most often occur as a result of a frequency leak—this is just extraneous RF radiation detected by the receiver coil. Notice that the line of artifact is off-center, indicating that the fundamental frequency is different from the Larmor frequency of the MRI system, which is what you would expect from an extraneous source....
The Russian Adriatic
Authors: Zanou Konstantina
Published: December 2018

Chapter 4 explores Russia’s imperial ambitions and military conduct in the Mediterranean during the second half of the eighteenth and the first half of the nineteenth centuries. It focuses on the endeavour of the ‘Septinsular Republic’ (1800–7), a constitutional aristocratic, semi-independent statelet, which put the Ionian islands under the sovereignty of the Porte and the direct political and military protection of Russia. It presents the main characters who staffed this short-lived polity—namely, Giorgio Mocenigo, Ioannis Kapodistrias, Spiridione Naranzi, Andrea Mustoxidi, and Bishop Ignatius—and argues that Russia’s political and military conduct in the Mediterranean, and particularly in the Ionian Adriatic, had a strong impact on the way national and liberal ideas were developing in the area.
The Utility and Construct Validity of Four Measures of Pain Intensity: Results from a University-Based Study in Spain
Authors: Jensen Mark P , Castarlenas Elena , Roy Rubén , Tomé Pires Catarina , Racine Mélanie , Pathak Anupa , Miró Jordi
Published: December 2018

Objective

Pain intensity is the most commonly assessed domain in pain research and clinical settings. To facilitate cross-cultural research, knowledge regarding the psychometric properties of pain intensity measures in individuals from different countries is needed. However, the majority of this research has been conducted in English-speaking countries.

Design

Survey study.

Setting

University.

Subjects

Four hundred nineteen college students.

Methods

Participants were asked to complete four measures assessing average pain intensity: 1) the 0–10 numerical rating scale (NRS-11), 2) the 100-mm visual analog scale (VAS), 3) the four-point verbal rating scale (VRS-4), and 4) the Faces Pain Scale–Revised (FPS-R).

Results

The rates of incorrect completion of the four scales were uniformly low (range = 1–2%). The NRS-11 had the highest preference rate (31%), although a substantial number of participants also preferred each of the other three scales (range = 22–24%). The findings support the utility and construct validity of all four pain intensity scales in this Spanish-speaking sample.

Conclusions

When considered in light of research from other non-English-speaking samples indicating significant psychometric weaknesses for the NRS-11 and VAS and relative strengths of the FPS-R in some groups, the findings suggest that the FPS-R might be the most appropriate pain intensity scale to use when comparisons across populations from different countries is a goal. More research is needed to determine the extent to which demographic (i.e., age, education levels, socioeconomic status) vs cultural factors (i.e., country of origin) influence the reliability, validity, and utility of different pain measures.
Developmental Trajectories and Reference Percentiles for Range of Motion, Endurance, and Muscle Strength of Children With Cerebral Palsy
Authors: Jeffries Lynn M , LaForme Fiss Alyssa , Westcott McCoy Sarah , Bartlett Doreen , Avery Lisa , Hanna Steven ,   On Track Study Team
Published: December 2018

Background

Children with cerebral palsy (CP) frequently present with secondary impairments in spinal alignment and extremity range of motion, endurance for activity, and muscle strength. Creation of developmental trajectories for these impairments will help guide clinical decision-making.

Objective

For children in each level of the Gross Motor Function Classification System (GMFCS) this study aimed to: (1) create longitudinal developmental trajectories for range of motion (Spinal Alignment and Range of Motion Measures [SAROMM]), endurance (Early Activity Scale for Endurance [EASE]), and functional strength (Functional Strength Assessment [FSA]); and (2) develop age-specific reference percentiles and amount of change typical over 1 year for these outcomes.

Design

This study used a longitudinal cohort design.

Methods

Participants comprised 708 children with CP across GMFCS levels, aged 18 months up to the 12th birthday, and their families. In 2 to 5 assessments every 6 months over 2 years, trained therapists performed the SAROMM and FSA, and parents completed the EASE questionnaire. For children in each GMFCS level, longitudinal trajectories using linear and nonlinear mixed-effects models from all visits, and reference percentiles using quantile regression from the first, 12-month, and 24-month visits were created for each measure.

Results

Longitudinal trajectories and percentile graphs for SAROMM, FSA, and EASE were primarily linear, with different performance scores among GMFCS levels. There was much variability in both longitudinal trajectories and percentiles within GMFCS levels.

Limitations

Limitations included a convenience sample and varying numbers of participants assessed at each visit.

Conclusions

The longitudinal trajectories and percentile graphs have application for monitoring how children with CP are performing and changing over time compared with other children with CP. The resources presented allow therapists and families to collaboratively make decisions about intervention activities targeted to children's unique needs.
Gout Activity Score has predictive validity and is sensitive to change: results from the Nottingham Gout Treatment Trial (Phase II)
Authors: Chinchilla Sandra P , Doherty Michael , Abhishek Abhishek
Published: December 2018

Objectives

To examine the predictive validity of the Gout Activity Score (GAS), its correlation with the Gout Impact Scale (GIS) and their sensitivity to change.

Methods

Data from a clinical trial in which participants with one or more gout flares in the previous year were recruited from primary care and randomized to nurse-led or continuing usual care were used in this study. GAS and GIS were calculated as described, with higher scores indicating worse disease activity and quality of life, respectively. The correlation between GAS and GIS was examined using Spearman’s correlation. Standardized response means (SRMs) were calculated to assess sensitivity to change. The association between GAS at baseline and the number of flares in the next 12 months was evaluated using Poisson regression. Data analyses were performed using STATA version 14, with P-values <0.05 being statistically significant.

Results

There was low positive correlation between GAS and gout concern overall and unmet treatment need subscales of GIS (r = 0.34–0.45). Female sex associated independently with fewer gout flares, while increasing GAS, BMI and age associated independently with frequent flares. Of all the outcome measures examined, GAS was the most responsive to change (SRM 0.89 to −0.53). Of the GIS domains, the gout concern overall domain had the best sensitivity to change (SRM 1.06–0.01).

Conclusion

GAS is sensitive to change, has predictive validity and correlates with relevant domains of GIS such as gout concern overall. Additional independent validation of GAS is required before it can be adopted in clinical practice.
Curare: The Poisoned Arrow that Entered the Laboratory and Sparked a Moral Debate
Authors: Shmuely Shira
Published: December 2018

Curare, a paralysing poison derived from South American plants, fascinated European explorers with its deadly powers. Generations of travellers were perplexed by how animals affected by curare showed no signs of suffering. British experimenters relabelled curare as an anaesthetic and used it to restrain animals during experiments. But during the 19th century, doubts started to appear: can a paralysed animal feel pain but be unable to express it? A scientific dispute emerged as not all British physiologists accepted Claude Bernard’s claim that curare affected only the motor nerves. The scientific controversy over curare reached the British parliament, and the Cruelty to Animals Act (1876) stated that curare would not be considered an anaesthetic. Nevertheless, antivivisection advocates continued to contest its use for decades. The article reveals new aspects of colonial import of bioactive plants in a case that reshaped the production of medical knowledge and presented epistemological and moral challenges.
Symbiotic Performance of Sinorhizobium meliloti Lacking ppGpp Depends on the Medicago Host Species
Authors: Wippel Kathrin , Long Sharon R.
Published: December 2018

Host specificity in the root-nodule symbiosis between legumes and rhizobia is crucial for the establishment of a successful interaction and ammonia provision to the plant. The specificity is mediated by plant-bacterial signal exchange during early stages of interaction. We observed that a Sinorhizobium meliloti mutant ∆relA, which is deficient in initiating the bacterial stringent response, fails to nodulate Medicago sativa (alfalfa) but successfully infects Medicago truncatula. We used biochemical, histological, transcriptomic, and imaging approaches to compare the behavior of the S. meliloti ∆relA mutant and wild type (WT) on the two plant hosts. ∆relA performed almost WT-like on M. truncatula, except for reduced nitrogen-fixation capacity and a disorganized positioning of bacteroids within nodule cells. In contrast, ∆relA showed impaired root colonization on alfalfa and failed to infect nodule primordia. Global transcriptome analyses of ∆relA cells treated with the alfalfa flavonoid luteolin and of mature nodules induced by the mutant on M. truncatula revealed normal nod gene expression but overexpression of exopolysaccharide biosynthesis genes and a slight suppression of plant defense-like reactions. Many RelA-dependent transcripts overlap with the hypo-osmolarity–related FeuP regulon or are characteristic of stress responses. Based on our findings, we suggest that RelA is not essential until the late stages of symbiosis with M. truncatula, in which it may be involved in processes that optimize nitrogen fixation.
Patient perspectives in gout: a review
Authors: Singh Jasvinder A.
Published: December 2018

Purpose of review

Recent studies have produced evidence regarding the patient perspectives in gout including from disease experience to disease outcomes. Therefore, an overview on the topic can help improve our understanding of the patient experience.

Recent findings

This article explores several aspects of the patient perspective including the impact of gout on a patient's life, patient knowledge and beliefs regarding gout and its treatments, patient-perceived barriers to optimal medication adherence in gout and patient's perception of their gout. This article also summarizes any evidence of the association of patient perceptions to patient outcomes in gout.

A recognition of patient perspectives in gout has the potential to positively impact clinical care for gout. Discussion of disease impact, misperceptions about benefits/harms of urate-lowering therapy (ULT), and patient values/preferences regarding pharmacological and nonpharmacological treatments can lead to a better shared decision-making and improved outcomes in gout. These findings emphasize the importance of inclusion of patient perspective not only in clinical care and quality improvement and research initiatives but also in the design and implementation of the research agenda in gout. Inclusion of patient-reported outcomes in clinical research is likely to improve its relevance to patients with gout.
Novel Immunotherapeutic Agents for the Treatment of Multiple Myeloma
Authors: Rafei Hind , Haroun Faysal , Tabbara Imad A.
Published: December 2018

Multiple myeloma (MM) is a B-cell malignancy characterized by the abnormal proliferation of clonal plasma cells in the bone marrow leading to end-organ manifestations. Despite the advancement in the therapy and care of patients with MM, relapse and resistance to standard therapy remain significant. The development of immunotherapy as a treatment modality for many types of cancers has led investigators to explore its use in MM in order to elicit myeloma-targeted immune responses, especially given that immune dysregulation is an underlying feature in the pathogenesis and progression of MM. In this concise review, we discuss the different advances in the immune-based therapy of MM, from immunomodulation, vaccines, to monoclonal antibodies, checkpoint inhibitors, adoptive T-cell therapies, and future promising therapies under investigation.
Concurrent Radiosurgery and Immune Checkpoint Inhibition
Authors: Murphy Blair , Walker Joshua , Bassale Solange , Monaco Debra , Jaboin Jerry , Ciporen Jeremy , Taylor Matthew , Dai Kubicky Charlotte
Published: December 2018

Objectives:

The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control.

Methods:

We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined.

Results:

In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed.

Conclusions:

Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.
QUANTIFICATION OF RETINAL CAPILLARY NONPERFUSION IN DIABETICS USING WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Alibhai A. Yasin , De Pretto Lucas R. , Moult Eric M. , Or Chris , Arya Malvika , McGowan Mitchell , Carrasco-Zevallos Oscar , Lee ByungKun , Chen Siyu , Baumal Caroline R. , Witkin Andre J. , Reichel Elias , de Freitas Anderson Zanardi , Duker Jay S. , Fujimoto James G. , Waheed Nadia K.
Published: December 2018

Purpose:

To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR).

Methods:

Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion.

Results:

The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0–0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2–3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0–14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR.

Conclusion:

Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.
MANAGEMENT OF GIANT RETINAL TEARS USING TRANSSCLERAL DIODE LASER RETINOPEXY AND SHORT-TERM POSTOPERATIVE TAMPONADE WITH PERFLUORO-N-OCTANE
Authors: Bhardwaj Gaurav , Connell Paul P. , Campbell William G.
Published: December 2018

Purpose:

To determine the results of pars plana vitrectomy for giant retinal tear detachments using transscleral diode laser retinopexy and short-term postoperative tamponade with perfluoro-n-octane (PFnO).

Methods:

Twenty consecutive patients with fresh giant retinal tears were enrolled in a single-arm prospective study. One case was withdrawn for technical reasons. The remainder all underwent pars plana vitrectomy, PFnO injection, transscleral diode laser retinopexy to the edge of the giant retinal tear, and short-term postoperative heavy liquid tamponade. None of the cases had scleral buckling or lensectomy.

Results:

Nineteen cases (18 male and 1 female) with a mean age of 41 years (range 10–69 years) were followed up for a period of 6 months. Postoperative tamponade with PFnO was maintained for a mean of 7.6 days (range 4–21 days), after which it was exchanged for sulfur hexafluoride (SF6), perfluoropropane (C3F8) gas, or balanced salt solution. Final reattachment rate was 100%, with 3 (15.7%) patients requiring additional surgery. Best-corrected visual acuity at final follow-up was 20/40 or better in 11 eyes (58%), between 20/60 and 20/200 in 7 (37%), and 20/400 in 1 (5%).

Conclusion:

In this series of acute giant retinal tears, transscleral diode laser retinopexy together with the use of PFnO for short-term postoperative tamponade achieved excellent anatomical and visual results.
Deep Anterior Lamellar Keratoplasty in a Case of Hurler–Scheie Syndrome Undergoing Enzyme Replacement Therapy
Authors: Eah Kyu Sang , Lee Chang Mok , Kim Myoung Joon
Published: December 2018

Purpose:

To report successful management of corneal clouding associated with Hurler–Scheie syndrome with deep anterior lamellar keratoplasty (DALK) undergoing concurrent enzyme replacement therapy (ERT).

Methods:

A 13-year-old boy with Hurler–Scheie syndrome (MPS I-HS) presented with corneal clouding in both eyes. He was on ERT with laronidase (Aldurazyme; Genzyme, Cambridge, MA) and had a visual acuity of 20/32 in both eyes. Seven years later, visual acuity in his left eye decreased to counting fingers and DALK was performed for vision recovery. Two years later, visual acuity in his right eye decreased to 20/100 and DALK was performed.

Results:

At his last visit, which was 3 years after right eye DALK and 5 years after left eye DALK, the grafts were clear and the corrected visual acuity in his right and left eyes was 20/30 and 20/25, respectively.

Conclusions:

The present case highlights the possible effectiveness of DALK in patients with mucopolysaccharidosis (MPS)-related corneal stromal opacification, treated with ERT.
A Comparative Content Analysis of Digital Channels for Ventricular Assist Device Patients, Caregivers, and Healthcare Practitioners
Authors: Ko Keum Hee Kimmi , Dunn Jessica Lea , Straker Karla , Nusem Erez , Gregory Shaun , Wrigley Cara
Published: December 2018

This article seeks to review and analyze the emergence of digital channels designed for ventricular assist device (VAD) patients, caregivers, and practitioners and to understand how such digital channels support the user experience of VAD implantation. Following a content analysis methodology, the authors investigated 16 digital channels designed for VAD patients, caregivers, and practitioners, with data being analyzed thematically. Competitor Positioning Matrix diagrams were created to visually represent the landscape of digital channels that support VAD stakeholders. These matrices identified opportunities and potential areas for improvement in future VAD digital channel design, with an emphasis on interactivity coupled with intelligence and focus along the various stages of the VAD patient journey. Innovation in digital channels has the potential to reduce burden on all users by enabling communication, self-management, and remote monitoring. Digital channels can be information enhanced for point of care, function as a decision support tools or be used to empower patient-caregiver pairs to be more sufficient with self-management, while enabling communication with their practitioner.
Left Ventricular Assist Device Outflow Graft Obstruction: A Complication Specific to Polytetrafluoroethylene Covering. A Word of Caution!
Authors: Alnabelsi Talal , Shafii Alexis E. , Gurley John C. , Dulnuan Kenneth , Harris II Dwight D. , Guglin Maya
Published: December 2018

Pump thrombosis is an established complication of left ventricular assist devices (LVADs). Outflow graft obstruction has been previously described as one cause of LVAD thrombosis. We identified four cases of outflow graft obstruction that were attributed to a commonly applied polytetrafluoroethylene (PTFE) covering of the outflow graft. In this set of patients, the outflow graft was obstructed by a thrombus which formed between the outflow graft and its external PTFE covering, leading to impingement of the outflow graft. Patients typically presented after a median duration of 26 months (range 23–41 months) of support with gradual increase of heart failure symptoms and low pump flows. Computed tomography angiography was found to be the best diagnostic modality. Treatments included surgical LVAD replacement as well as percutaneous intraluminal stenting of the outflow graft. Our findings indicate that PTFE graft covering of the LVAD outflow graft can lead to graft occlusion and should be reconsidered as a potentially harmful modification to the approved device implant technique.
Management of Functional Esophagogastric Junction Outflow Obstruction
Authors: Garbarino Stephanie , von Isenburg Megan , Fisher Deborah A. , Leiman David A.
Published: December 2018

Goals:

Awareness of functional esophagogastric junction outflow obstruction (fEGJOO) has increased, but because there is no consensus on its management, we performed a systematic review of the literature to explore treatment strategies and outcomes.

Background:

EGJOO is a heterogenous disorder defined by high-resolution manometry parameters of elevated integrated relaxation pressure with preserved esophageal peristalsis. The etiology may be mechanical obstruction or idiopathic, the latter being fEGJOO.

Study:

The PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through June 2018 for all studies of adult patients describing a treatment strategy for fEGJOO or incomplete lower esophageal sphincter relaxation. The search strategy yielded 1792 studies and 8 (0.4%) met inclusion criteria.

Results:

All but one included studies were retrospective (n=184 patients). There were 5 interventions described, with botulinum toxin (Botox) injection (n=69) and expectant management (n=82) the most frequently reported, with success rates of 58% and 54%, respectively. There was substantial heterogeneity among patients and treatments were not directly compared, though reported symptom resolution was similar among all strategies with a mean follow-up time of 15 months.

Conclusions:

There are a variety of management strategies available for fEGJOO and some patients may not require any intervention. However, among 4 potential approaches aimed at disrupting lower esophageal sphincter hypertonicity, the largest existing evidence base supports either a therapeutic challenge of Botox injection or watchful waiting. Ultimately, these data indicate the need for further study with controlled trials to identify a definitive approach.
Second-line Treatments of Advanced Hepatocellular Carcinoma
Authors: Bakouny Ziad , Assi Tarek , El Rassy Elie , Nasr Fadi
Published: December 2018

Background:

Advanced hepatocellular carcinoma (HCC) constitutes the second leading cause of cancer-related deaths. First-line therapy is either sorafenib or lenvatinib. Several treatment options have been recently added to the second-line treatment of advanced HCC. The aim of this network meta-analysis of randomized controlled trials was to compare the second-line treatments of advanced HCC.

Methods:

Network meta-analyses were computed for overall survival (OS), progression-free survival, rates of grade 3 to 5 adverse events, and for treatment discontinuation due to adverse events. OS was considered to be the primary outcome of this study, and everolimus was chosen to be the common comparator for efficacy analyses and placebo for safety analyses. Subgroup analyses were computed for OS in patients with hepatitis B, patients with hepatitis C, Asian patients, patients with macrovascular invasion, and patients with extrahepatic metastases.

Results:

Thirteen randomized controlled trials including 5076 patients and evaluating 11 agents were found to be eligible. Regorafenib [hazard ratio (HR)=0.60, 95% confidence interval (CI)=0.44-0.81] and cabozantinib (HR=0.72, 95% CI=0.55-0.95) were found to significantly prolong OS compared with everolimus. The effect of regorafenib on OS tended to be conserved across patient subgroups. Regorafenib was also found to significantly prolong progression-free survival (HR=0.46, 95% CI=0.35-0.62) and significantly increase the rates of grade 3 to 5 adverse events (odds ratios=3.18, 95% CI=2.22-4.54) and treatment discontinuation due to adverse events (odds ratios=2.67, 95% CI=1.21-5.87).

Conclusions:

This network meta-analysis concludes that, based on current evidence, regorafenib could be the agent of choice in the second-line treatment of HCC, with cabozantinib as a possible alternative for sorafenib-intolerant patients.
Acute Liver Failure
Authors: Doulberis Michael , Kotronis Georgios , Gialamprinou Dimitra , Özgüler Onur , Exadaktylos Aristomenis K. , Oikonomou Vasileios , Katsinelos Panagiotis , Romiopoulos Iordanis , Polyzos Stergios A. , Tzivras Dimitri , Deretzi Georgia , Dardiotis Efthimios , Kountouras Jannis
Published: December 2018

Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available.
Scientific Registry of Transplant Recipients program-specific reports: where we have been and where we are going
Authors: Kasiske Bertram L. , Salkowski Nicholas , Wey Andrew , Israni Ajay K. , Snyder Jon J.
Published: December 2018

Purpose of review

Reporting provider data on quality to patients and the general public is increasingly common in healthcare. Reporting outcomes in solid organ transplantation has always been controversial and deserves careful consideration to ensure optimal results.

Recent findings

As mandated by Federal law, the Scientific Registry of Transplant Recipients publishes program-specific reports on transplant candidates, recipients, donors, and transplant outcomes every 6 months. Recent changes designed to make the results more easily understood by patients and the general public have been well received by patients and controversial among providers. In particular, outcomes are now reported using a five-tier system that distinguishes program results better than the old three-tier system, in which almost all programs were reported “as expected.” Metrics that reflect access to transplant are also reported, including transplant rate and survival on the waiting list. Possible measures of longer term outcomes and program rates of accepting organs for transplant are being explored.

Providing detailed information regarding transplant program practices and outcomes in ways that patients and the general public can understand remains a major focus of the Scientific Registry of Transplant Recipients. Efforts to improve data collection and metrics reported are ongoing.
“I’m a Survivor”
Authors: Meiklejohn Judith A. , Bailie Ross , Adams Jon , Garvey Gail , Bernardes Christina M. , Williamson Daniel , Marcusson Beverly , Arley Brian , Martin Jennifer H. , Walpole Euan T. , Valery Patricia C.
Published: December 2018

Background

Disparity in outcomes between Indigenous and non-Indigenous people after cancer diagnosis is multifactorial, including lower cancer screening participation, later diagnosis, reduced access and uptake of cancer treatment, higher rate of comorbidities, and barriers accessing the health system. Little is known about cancer survivorship experiences.

Objective

The aim of this study was to explore Indigenous Australian cancer survivor's perspectives of cancer survivorship.

Methods

Indigenous people who completed cancer treatment 6 months to 5 years before fieldwork were recruited from a tertiary hospital and remote primary health service for this qualitative study. Data collection was guided by yarning methods, a culturally appropriate method emphasizing storytelling. Data were interpreted using a social constructionist framework.

Results

Thirteen women and 6 men were interviewed. Participants' past experiences contributed to their specific identity as survivors. Participants described factors affecting a positive transition from cancer patient to cancer survivor and the importance of ongoing family support in helping to manage survivorship. Finally, participants described a range of community support they received and provided to others and how this improved their cancer survivorship.

Conclusion

Although a range of experiences are presented, this study provides evidence that the survivorship perspectives of Indigenous cancer survivors may be, in part, shared by non-Indigenous cancer survivors.

Implications for Practice

Acknowledging Indigenous cancer survivors' past experiences and how these influence their overall well-being is important for providing patient-centered and culturally appropriate care. Nurses and other healthcare professionals may use this knowledge to foster a range of coping strategies to assist Indigenous cancer survivors to live well.
The Role of Interpersonal Problems and Family Environment in the Association Between Impulsivity and Suicidal Ideation
Authors: Wang Chenxu , Mo Juanchan , Niu Xiaoxiao , Jia Xuji , Lin Lin
Published: December 2018

Impulsivity, interpersonal problems, and family environment are important factors in the development of suicidal ideation, but the pathway of these factors on suicidal ideation is not clear. This study constructed a moderated mediation model to examine whether interpersonal problems mediated the relationship between impulsivity and suicidal ideation and whether this mediating process was moderated by family environment. For this purpose, 902 college students from Tianjin Normal University located in the north of China were recruited to participate in this study with Barratt Impulsiveness Scale, Adolescent Self-Rating Life Events Check List, Family Environment Scale, and Beck Scale for Suicidal Ideation. Impulsivity could significantly predict suicidal ideation, and the relationship between impulsivity and suicidal ideation was significantly mediated by interpersonal problems; furthermore, the mediating effect and the directing effect were significantly moderated by family environment. These findings contribute to our understanding of a comprehensive interpretation of both environmental and individual factors' impacts on suicidal ideation.
The Risk of Suicide and Self-Harm in Adolescents Is Influenced by the “Type” of Mood Disorder
Authors: Parker Gordon , Ricciardi Tahlia
Published: December 2018

We sought to examine the extent to which suicidal ideation and self-harm are associated with a set of psychiatric conditions in senior high school students. A total of 1577 students completed an anonymous survey assessing lifetime rates of mood, anxiety, and eating disorders; the extent to which the presence of any depressive condition attracted bullying; help-seeking strategies; as well as rates of self-harm and suicidal ideation and plans over differing periods. Suicidal ideation and plans together with self-harm rates were distinctly higher in those with a melancholic depressive or a bipolar disorder (compared with those with nonmelancholic depression or an anxiety or eating disorder) and generally higher in females, whereas numbers of those with such conditions attending a mental health professional were low. Thus, for those with a mood disorder, the type of the condition appears to have a distinct impact on the likelihood of suicide and self-harm.
Simultaneous Versus Sequential Heart-liver Transplantation: Ideal Strategies for Organ Allocation
Authors: Rucker A. Justin , Anderson Kevin L. , Mulvihill Michael S. , Yerokun Babatunde A. , Barbas Andrew S. , Hartwig Matthew G.
Published: December 2018

Background

Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL.

Methods

The Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research file was queried for adult recipients waitlisted for both heart and liver transplantation. The United Network for Organ Sharing thoracic and liver databases were linked to facilitate examination of waitlist and transplant characteristics for simultaneously listed patients. Univariate survival analysis was used to determine overall survival.

Results

Of the 236 patients meeting inclusion criteria, 200 underwent SHL, 7 sequentially underwent LAH, and 29 received heart transplantation only (isolated orthotopic heart transplantation [iOHT]). Recipients of SHL were less likely to have an episode of acute rejection before discharge (LAH, 14.2%; SHL, 2.4%; iOHT, 3.6%; P = .019) or be treated for acute rejection within 1 year after transplantation (LAH, 14.3%; SHL, 2.5%; iOHT, 13.8%; P = .007). Otherwise, postoperative hospital length of stay, stroke, need for dialysis, and need for pacemaker placement were comparable across groups. Ten-year survival similarly favored both LAH and SHL over iOHT (LAH: 100%, 71.4%, 53.6%; SHL: 87.1%, 80.4%, 52.1%, iOHT: 70.1%, 51.6%, 27.5% for 1-, 5-, and 10-year survivals, respectively, P = .003). However, median time between heart and liver transplant was 302 days in patients undergoing sequential transplantation.

Conclusions

Although transplantation in a simultaneous or sequential fashion yields equivalent outcomes, a high fraction of patients undergoing initial heart transplant alone fail to proceed to subsequent liver transplantation. Therefore, in patients with combined heart and liver failure with a projected need for 2 allografts, simultaneous transplantation is associated with maximum benefit.
Effects of varenicline and cognitive bias modification on neural response to smoking-related cues: a randomised control trial
Authors: Attwood Angela S , Williams Tim M , McClernon F. Joseph , Kozink Rachel , Adams Sally , Scheeres Karl , Green Amy , Christmas David , Munafo Marcus R
Published: December 2018

Drug-related cognitive biases have been positively associated with drug-craving and increased likelihood of relapse. Cognitive bias modification paradigms have been developed to attenuate cognitive biases but there have been few studies that examined neural responses to these paradigms. This study compared neural responses following CBM and explored whether CBM effects were potentiated by varenicline administration. This was a double-blind placebo-controlled study with two between subject factors of drug (varenicline, placebo) and CBM (attend towards smoking cues, train away from smoking cues, control training) that recruited daily (> 10 cigarettes per day) non-treatment seeking smokers. Participants (n = 67, 53% female) were randomised to one-week of drug administration (varenicline or placebo) before attending a study session at which they were randomised to CBM condition, and underwent an fMRI scan were they were presented with smoking and neutral cues. Neural response to smoking (vs. neutral) cues, cognitive bias, craving and mood were assessed. There was no evidence of CBM effects on any outcomes. There was evidence of effects of varenicline on craving, with greater reductions in craving in the week preceding the study session in the varencline group (p = 0.04, ηp2 = .06). There was also evidence of a drug by CBM interaction for neural responses (z = 3.78, p <0.001). Compared to placebo, varenicline was associated with greater activation in the right temporal middle gyrus in the CBM control condition, compared to an opposite effect in the CBM attend towards condition. These data suggest that CBM does not modify cognitive bias, subjective craving and mood, or neural response to smoking cues. There was also no evidence that CBM effects were potentiated by varenicline. Clinical trial registration ID #ISRCTN65690030
Detailed analysis of paternal knockoutGrb10mice suggests effects on stability of social behavior, rather than social dominance
Authors: Rienecker Kira D. A. , Chavasse Alexander T. , Moorwood Kim , Ward Andrew , Isles Anthony R.
Published: December 2018

Imprinted genes are highly expressed in monoaminergic regions of the midbrain and their functions in this area are thought to have an impact on mammalian social behaviors. One such imprinted gene isGrb10, of which the paternal allele is currently recognized as mediating social dominance behavior. However, there has been no detailed study of social dominance inGrb10+/pmice. Moreover, the original study examined tube-test behavior in isolated mice 10 months of age. Isolation testing favors more territorial and aggressive behaviors, and does not address social dominance strategies employed in group housing contexts. Furthermore, isolation stress impacts midbrain function and dominance related behavior, often through alterations in monoaminergic signaling. Thus, we undertook a systematic study ofGrb10+/psocial rank and dominance behavior within the cage group, using a number of convergent behavioral tests. We examined both male and female mice to account for sex differences, and tested cohorts aged 2, 6, and 10 months to examine any developments related to age. We found group-housedGrb10+/pmice do not show evidence of enhanced social dominance, but cages containingGrb10+/pand wildtype mice lacked the normal correlation between three different measures of social rank. Moreover, a separate study indicated isolation stress induced inconsistent changes in tube test behavior. Taken together, these data suggest future research onGrb10+/pmice should focus on on the stability of social behaviors, rather than dominanceper se.
Optimising multi-batch TMT analysis to mitigate inflation of missing values, false positives and diminished inter batch accuracy
Authors: Brenes Alejandro , Hukelmann Jens L , Bensaddek Dalila , Lamond Angus I
Published: December 2018

Multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent, TMT in particular. Here we used a large iPSC proteomic experiment with twenty-four 10-plex TMT batches to evaluate the effect of integrating multiple TMT batches within a single analysis. We reveal a significant inflation rate of missing protein and peptide values and show that precision decreases as multiple batches are integrated. Additionally, we explore the effect of false positives using Y chromosome specific peptides as an internal control to quantify the effect of co-isolation interference, as well as primary and secondary reporter ion interference. Based on the results we suggest solutions to mitigate these effects. We show using a reference line can increase precision by normalising the quantification across batches and we propose experimental designs that minimise the effect of cross population reporter ion interference.
An Adhesive Interface for the Non-Clustered δ1 Protocadherin-1 Involved in Respiratory Diseases
Authors: Modak Debadrita , Sotomayor Marcos
Published: December 2018

Cadherins form a large family of calcium-dependent adhesive proteins involved in morphogenesis, cell differentiation, and neuronal connectivity. Non-clustered δ1 protocadherins form a cadherin subgroup of proteins with seven extracellular cadherin (EC) repeats and cytoplasmic domains distinct from those of classical cadherins. The non-clustered δ1 protocadherins mediate homophilic adhesion and have been implicated in various diseases including asthma, autism, and cancer. Here we present X-ray crystal structures of Protocadherin-1 (PCDH1), a δ1-protocadherin member essential for New World hantavirus infection that is typically expressed in the brain, airway epithelium, skin keratinocytes, and lungs. The structures suggest a binding mode that involves antiparallel overlap of repeats EC1 to EC4. Mutagenesis combined with binding assays and biochemical experiments validated this mode of adhesion. Overall, these results reveal the molecular mechanism underlying adhesiveness of PCDH1 and δ1-protocadherins, also shedding light on PCDH1’s role in maintaining airway epithelial integrity, the loss of which causes respiratory diseases.