bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic laboratory techniques
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

A modern genomic laboratory will offer a range of diagnostic techniques. A biochemical genetic laboratory may also be based in selected centres. In this chapter, a brief account of diagnostic techniques that are useful for inherited cardiac diseases is provided. It covers variant classification and techniques that can detect DNA sequence variants, next generation sequencing, Sanger sequencing, copy number analysis (including whole genome copy number analysis), targeted dosage techniques, and known variant detection. It then gives examples of genetic laboratory reports in the context of investigating potential inherited cardiac diseases, with subsequent familial tests if required.
Marfan syndrome and related inherited disorders of connective tissue
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

The phenotype of inherited disorders of connective tissue is extensive and may involve multiple body systems. In most cases, the clinical picture is that of a progressive chronic disease with mild to severe dermatological, osteo-articular, ocular, and cardiovascular manifestations. The spectrum of cardiovascular manifestations is broad and may range from a mild structural abnormality (e.g. mitral incompetence) to life-threatening complications (e.g. aortic dissection). This chapter provides a general guide to diagnosis and management of cardiovascular manifestations in Marfan syndrome and related inherited disorders of connective tissue. Major conditions are discussed in detail and the interested reader is advised to consult online resources for information on other less common inherited connective tissue disorders
Hereditary haemorrhagic telangiectasia
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

The genetics of hereditary haemorrhagic telangiectasia (HHT)—previously known as Rendu–Osler–Weber syndrome—is covered in this chapter, with identified HHT disease-causing genes listed, the clinical features described, and finally treatment options are listed.
Diagnosis
Authors: Aletaha Daniel , Radner Helga
Published: September 2020

Rheumatoid arthritis (RA) affects approximately 1% of the adult population. It is currently considered a chronic disease for which there is no cure, but remission has become an achievable goal with optimal treatment. Both disability and enormous cost are functions of the disease over time. It is therefore crucial to treat RA early and persistently until remission is present. The challenge of treatment of early RA is not the lack of effective medicine, but rather the ethical and economic considerations related to risk-benefit and cost-benefit. Overtreating patients with disease-modifying antirheumatic drugs (DMARDs) is often feared, but the potential undertreatment of patients with RA can have accelerated structural consequences. This chapter covers diagnosis of RA, from the initial evaluation of patients with new-onset arthritis to important differential diagnoses. Critical diagnostic features are explained, and the 2010 European League Against Rheumatism (EULAR) classification criteria are described and rationalized. The importance of distinction between classification and diagnosis is highlighted.
Magnetic resonance imaging in rheumatoid arthritis
Authors: Østergaard Mikkel , Conaghan Philip G. , Peterfy Charles
Published: September 2020

In rheumatoid arthritis (RA), early diagnosis combined with early initiation of appropriate therapy and tight control of inflammation have been recognized as essential for optimal clinical outcomes. Conventional radiography, though able to detect structural joint damage in patients with established disease, is not sensitive in detecting early disease manifestations such as soft tissue changes and bone damage at its earliest stages. Magnetic resonance imaging (MRI) allows multiplanar tomographic imaging of the body in any plane without geometric distortions associated with projectional techniques, such as radiography, and no ionizing radiation is used. Early bone involvement and inflammatory soft tissue changes of synovitis and tenosynovitis, which are not detectable by conventional clinical, biochemical, and radiographic methods, can be directly visualized and evaluated in detail by MRI. MRI is an increasingly available sensitive technique which has documented utility in the diagnosis, monitoring, and prognostication of patients with RA, and important new knowledge and technical improvements are continuously being acquired.
Fatigue
Authors: Dures Emma , Basu Neil
Published: September 2020

Fatigue in rheumatoid arthritis (RA) is associated with inflammation, pain, disability, sleep, depression, and health beliefs, implying complex, multicausal pathways comprising differing combinations of variables. From a patient perspective, it is a common, overwhelming, and distressing symptom. From a societal perspective, fatigue is a significant predictor of high healthcare costs and the main reason for work disability and loss. This chapter will highlight the role of patients in establishing the importance of the symptom, including the proposal that it should be measured in studies of RA whenever possible. Acknowledgement of fatigue as a patient priority is a relatively recent development, and highlights the value of collaborating with patients in shaping the research agenda. There will be discussion of the scale of fatigue in RA, including data on prevalence and descriptions of its nature and impact. Research has established the unpredictable and unearned nature of RA-related fatigue with its physical, cognitive, and emotional components, and identified the associated individual and societal burden. This will be followed by conceptual models informing our understanding of the biology of rheumatoid arthritis-related fatigue, the role of bioinformatics, and the challenges of unravelling the mechanisms of this multidimensional symptom. Finally, the evidence for interventions and treatments to alleviate fatigue will be presented, with a focus on non-pharmacological approaches to support fatigue self-management.
Translation of new therapies: From bench to bedside
Authors: Sokolove Jeremy
Published: September 2020

The process of drug development is often long and complex, often beginning at the bedside. This is related to the fact that the strongest evidence supporting the existence of a drug target in the human is the ability to demonstrate alteration of the target in the setting of disease relative to the healthy condition. The vast majority of compounds developed and tested die in the preclinical phase of drug development. A molecule targeting a pathway entering the clinic often has well over a decade of study behind it including work in academic and industry laboratories and even those which survive to enter Phase 1 human trials have a failure rate of over 90%. This chapter discusses the current process of drug development in rheumatology and immunology, including target and pathway identification.
Treatment targets and remission
Authors: Baker Kenneth F. , Pratt Arthur G.
Published: September 2020

The importance of achieving ‘tight control’ of rheumatoid arthritis (RA) through timely and sustained suppression of immune-mediated inflammation is now well-established. This is achievable through regular disease activity assessment and therapeutic adjustments against prespecified treatment targets—the treatment-to-target (T2T) strategy. Composite measures including joint assessments and patient-reported outcomes are typically used to define such targets, including the state of clinical remission which has become an increasingly achievable goal in recent years. The value of adjunctive imaging modalities and blood biomarkers as treatment target components, along with the associated concept of remission ‘depth’ and its clinical relevance, remain the subjects of debate. Beyond doubt is the profoundly beneficial effect that T2T adoption has had on disease outcomes. The increased prevalence of disease remission and, in some cases, its continuation even after therapeutic cessation now enables investigators to seek predictors of sustained, drug-free remission in RA for the first time.
Clinical outcomes
Authors: Scott David L.
Published: September 2020

The clinical outcomes measured in rheumatoid arthritis span three broad areas. Firstly, disease measures reflecting the presence and severity of joint inflammation. Secondly, end-organ damage particularly the extent and severity of joint damage. Thirdly, quality of life measures made by patients indicating the impact of their disease on their lives. Some are disease specific such as the Health Assessment Questionnaire (HAQ). Others are generic and applicable across all disease, such as the Short Form 36 (SF-36) and EuroQol. Several new patient-assessed outcome measures have been developed, such as the Patient-Reported Outcome Measurement Information System (PROMIS) and the Rheumatoid Arthritis Impact of Disease (RAID) score. Whether one of these new measures becomes dominant is currently uncertain. Clinical outcomes need to measure what is intended and have face, content, construct, and criterion validity. They also need to discriminate between states of interest reliably, exhibit sensitivity to change, and be easily measured and applied, given constraints of time, money, and interpretability. Different clinical outcomes are closely interrelated. Finally, clinical outcomes such as the EuroQol can be used to generate quality-adjusted life years (QALY), which are used in health economic studies. Measuring disease outcomes is essential for good medical care, which can only improve when clinicians know the results of their treatments and incorporate patients’ views.
Maternal physiology
Authors: Adekanye Korede , Theron Abrie
Published: September 2020

During pregnancy, maternal anatomy and physiology changes significantly. It is important to be aware of what is considered ‘normal’ for pregnancy, in order to promptly recognize and treat medical conditions that may subsequently develop in the antenatal, intrapartum, or postnatal time periods. This chapter sets out the anatomical and physiological changes according to each system: starting with a comprehensive review of the cardiovascular and respiratory changes, which have the most significant adaptations, through the renal, gastro-intestinal, haematological, and endocrine changes, and ending with the central nervous system. Altered anatomy and physiology will affect the conduct of general and regional anaesthesia. The difficulties associated with the obstetric airway, maternal oxygenation, and positioning during anaesthesia are clearly described.
Maternal pathophysiology
Authors: Adekanye Korede , Theron Abrie
Published: September 2020

It is well-recognized that there is an increasing cohort of pregnant women with complex co-morbidities, where an understanding of their underlying medical condition is fundamental to safe antenatal, peripartum, and anaesthesia management. This chapter begins with the principles of managing the woman with cardiac disease and comprehensively covers the different pathophysiology which may be present; from grown-up congenital heart disease and shunts, myocardial ischaemia, valvular lesions, aortopathy, and cardiomyopathies. The ideal physiological conditions are set out for each cardiac problem, with the potential for devastating complications highlighted. The anaesthetic planning and management of women with respiratory disease, renal impairment, haematological conditions, and diabetes is discussed in detail.
Obesity in pregnancy
Authors: Al-Foudri Huda , Davies Stuart , Theron Abrie
Published: September 2020

Epidemiological studies show the incidence of obesity in pregnancy to be increasing, and the management of the morbidly obese woman on labour ward can be a challenge for anaesthetists. The chapter defines obesity, body mass index, classification, and prevalence, and reviews the physiological effects of obesity on the respiratory, cardiovascular, gastrointestinal, renal, endocrine, and haematological systems, as well as pharmacokinetic changes. Both fetal and maternal morbidities are listed followed by management proposals in the antenatal, peripartum, and postpartum periods. This includes antenatal screening, criteria for anaesthetic referral for assessment and what this should include to plan for delivery. Suggestions for management during labour and during an operative delivery are made. Attention is given to the ramped position and enhanced pre-oxygenation prior to induction of general anaesthesia with CPAP and THRIVE. Practical considerations and technical challenges are discussed and include manual handling, IV access, monitoring, regional techniques, and previous bariatric surgery.
Major obstetric haemorrhageRachel Collis
Authors: Collis
Published: September 2020

Successful management of major obstetric haemorrhage requires a multi-professional team to work together to avoid catastrophic consequences: obstetricians, anaesthetists, midwives, ODPs, theatre scrub staff, porters, as well as blood bank technicians and specialist haematologists. The key pillars of management include; antenatal risk assessment of all women, early recognition of haemorrhage, measured blood loss, prompt escalation at specific trigger points, i.e. >500ml, >1000ml, and review by senior team members to ensure rapid source control. This chapter explores the causes of bleeding, management steps based on algorithms from current practice, and latest evidence for use of point of care testing with visco-elastography for goal-directed control of early clotting failure.
KLIFS: an overhaul after the first 5 years of supporting kinase research
Authors: Kanev Georgi K , de Graaf Chris , Westerman Bart A , de Esch Iwan J P , Kooistra Albert J
Published: September 2020

Kinases are a prime target of drug development efforts with >60 drug approvals in the past two decades. Due to the research into this protein family, a wealth of data has been accumulated that keeps on growing. KLIFS—Kinase–Ligand Interaction Fingerprints and Structures—is a structural database focusing on how kinase inhibitors interact with their targets. The aim of KLIFS is to support (structure-based) kinase research through the systematic collection, annotation, and processing of kinase structures. Now, 5 years after releasing the initial KLIFS website, the database has undergone a complete overhaul with a new website, new logo, and new functionalities. In this article, we start by looking back at how KLIFS has been used by the research community, followed by a description of the renewed KLIFS, and conclude with showcasing the functionalities of KLIFS. Major changes include the integration of approved drugs and inhibitors in clinical trials, extension of the coverage to atypical kinases, and a RESTful API for programmatic access. KLIFS is available at the new domain https://klifs.net.
Importance of base-pair opening for mismatch recognition
Authors: Bouchal Tomáš , Durník Ivo , Illík Viktor , Réblová Kamila , Kulhánek Petr
Published: September 2020

Mismatch repair is a highly conserved cellular pathway responsible for repairing mismatched dsDNA. Errors are detected by the MutS enzyme, which most likely senses altered mechanical property of damaged dsDNA rather than a specific molecular pattern. While the curved shape of dsDNA in crystallographic MutS/DNA structures suggests the role of DNA bending, the theoretical support is not fully convincing. Here, we present a computational study focused on a base-pair opening into the minor groove, a specific base-pair motion observed upon interaction with MutS. Propensities for the opening were evaluated in terms of two base-pair parameters: Opening and Shear. We tested all possible base pairs in anti/anti, anti/syn and syn/anti orientations and found clear discrimination between mismatches and canonical base-pairs only for the opening into the minor groove. Besides, the discrimination gap was also confirmed in hotspot and coldspot sequences, indicating that the opening could play a more significant role in the mismatch recognition than previously recognized. Our findings can be helpful for a better understanding of sequence-dependent mutability. Further, detailed structural characterization of mismatches can serve for designing anti-cancer drugs targeting mismatched base pairs.
Metamorphic Differentiation via Enhanced Dissolution along High Permeability Zones
Authors: Moore Jo , Beinlich Andreas , Piazolo Sandra , Austrheim Håkon , Putnis Andrew
Published: September 2020

Metamorphic differentiation, resulting in segregated mineral bands, is commonly recorded in metamorphic rocks. Despite the ubiquitous nature of compositionally layered metamorphic rocks, the processes that are responsible for metamorphic differentiation receive very little attention. Here, detailed petrography, quantitative mineral chemistry and bulk rock analyses are applied to investigate compositional variations and assemblage microstructure. Furthermore, thermodynamic modelling is applied to provide additional constraints on the P–T–XH2O conditions of assemblage formation and mass transfer. The studied outcrop, located within the Bergen arcs of southwestern Norway, preserves the hydration of anorthositic granulite at amphibolite-facies conditions. The amphibolite-facies hydration is expressed as both a statically hydrated amphibolite and a shear zone lithology, defined by the interlayering of amphibolite with leucocratic domains. Within the granulite, quartz-lined fractures surrounded by amphibolite-facies alteration haloes represent relics of initial fluid infiltration associated with brittle failure. The fracture assemblage (quartz + plagioclase + zoisite + kyanite ± muscovite ± biotite) is identical to that occurring within leucocratic domains of the shear zone. Consequently, the compositional layering of the shear zone lithology is linked to fluid infiltration along localized zones of high permeability that result from fracturing. Mass-balance calculations indicate that quartz-lined fractures and compositional differentiation of the shear zone resulted from mass redistribution internal to the shear zone rather than partial melting or precipitation of minerals from externally derived fluid. The process of internal fractionation within the shear zone is driven by enhanced dissolution along highly permeable fracture planes resulting in the loss of MgO, Fetot and K2O from the leucocratic domains. Elements dissolved in the fluid are then transported and ultimately either precipitated in comparatively impermeable amphibolite domains or removed from the system resulting in an overall mass loss. The mass transfer causing metamorphic differentiation of the shear zone is the result of coupled reaction and diffusion under differential stress. The mechanisms of mass redistribution observed within this shear zone provides further insight into the processes that facilitate mass transfer in the Earth’s crust.
Advances and prospects in biomimetic multilayered scaffolds for articular cartilage regeneration
Authors: Fu Liwei , Yang Zhen , Gao Cangjian , Li Hao , Yuan Zhiguo , Wang Fuxin , Sui Xiang , Liu Shuyun , Guo Quanyi
Published: September 2020

Due to the sophisticated hierarchical structure and limited reparability of articular cartilage (AC), the ideal regeneration of AC defects has been a major challenge in the field of regenerative medicine. As defects progress, they often extend from the cartilage layer to the subchondral bone and ultimately lead to osteoarthritis. Tissue engineering techniques bring new hope for AC regeneration. To meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue, a substantial number of multilayered biomimetic scaffolds have been studied. Ideal multilayered scaffolds should generate zone-specific functional tissue similar to native AC tissue. This review focuses on the current status of multilayered scaffolds developed for AC defect repair, including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue, the selection and composition of biomaterials, and techniques for design and manufacturing. The challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.
Zn-contained mussel-inspired film on Mg alloy for inhibiting bacterial infection and promoting bone regeneration
Authors: Peng Feng , Cheng Shi , Zhang Ruiying , Li Mei , Zhou Jielong , Wang Donghui , Zhang Yu
Published: September 2020

Infection and insufficient osteointegration are the main causes of orthopedic implant failure. Furthermore, activating favorable inflammation response is vital to the fast osteointegration of implants. Therefore, endowing the implants with multifunctions (antibacterial, anti-inflammation, and pro-osteointegration) is a promising strategy to improve the performance of orthopedic implants. In this study, a Zn-contained polydopamine (PDA) film was fabricated on AZ31 alloy. The film possessed a stable Zn ion release in 14 days. The results of electrochemical analysis implied the favorable corrosion protection of the film, and thus, leading to a suitable hemolysis ratio (below 1%). The in vitro antibacterial assessment revealed that the film exhibited excellent resistance against Staphylococcus aureus (nearly 100%), which can be ascribed to the release of Zn ions. The cell-culture evaluation revealed that the extract of Zn-contained PDA-coated sample can activate RAW264.7 polarization to an anti-inflammatory phenotype, as well as enhance the osteogenic differentiation ability of MC3T3-E1. Additionally, the femoral osteomyelitis model indicated that the as-prepared film had a high antibacterial capability at early stage of the implantation, and showed better osteogenesis and osteointegration after 8 weeks of implantation. With favorable antibacterial, anti-inflammation, and pro-osteogenesis abilities, the novel designed Zn-contained PDA film is promising to be used in Mg-based orthopedic implants.
Elucidation and refinement of synthetic receptor mechanisms
Authors: Edelstein Hailey I , Donahue Patrick S , Muldoon Joseph J , Kang Anthony K , Dolberg Taylor B , Battaglia Lauren M , Allchin Everett R , Hong Mihe , Leonard Joshua N
Published: September 2020

Synthetic receptors are powerful tools for engineering mammalian cell-based devices. These biosensors enable cell-based therapies to perform complex tasks such as regulating therapeutic gene expression in response to sensing physiological cues. Although multiple synthetic receptor systems now exist, many aspects of receptor performance are poorly understood. In general, it would be useful to understand how receptor design choices influence performance characteristics. In this study, we examined the modular extracellular sensor architecture (MESA) and systematically evaluated previously unexamined design choices, yielding substantially improved receptors. A key finding that might extend to other receptor systems is that the choice of transmembrane domain (TMD) is important for generating high-performing receptors. To provide mechanistic insights, we adopted and employed a Förster resonance energy transfer-based assay to elucidate how TMDs affect receptor complex formation and connected these observations to functional performance. To build further insight into these phenomena, we developed a library of new MESA receptors that sense an expanded set of ligands. Based upon these explorations, we conclude that TMDs affect signaling primarily by modulating intracellular domain geometry. Finally, to guide the design of future receptors, we propose general principles for linking design choices to biophysical mechanisms and performance characteristics.
Long-term Oncologic Impact of Positive Anterior and Posterior Surgical Margins After Radical Prostatectomy
Authors: Wu Shulin , Lin Sharron X. , Wirth Gregory J. , Lu Min , Lu Jian , Subtelny Alexander O. , Wang Zongwei , Olumi Aria F. , Dahl Douglas M. , Blute Michael L. , Wu Chin-Lee
Published: September 2020

Objective:

The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer.

Patients and Methods:

We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model.

Results:

There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed.

Conclusions:

In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.
Normal Saline and Lung Recruitment With Paediatric Endotracheal Suction
Authors: Schults Jessica A. , Cooke Marie , Long Debbie A. , Mitchell Marion L.
Published: September 2020

Background

Normal saline instillation (NSI) and lung recruitment manoeuvres (RMs) are used in conjunction with endotracheal suction (ETS) in mechanically ventilated children. Practice is varied, and it is not currently understood what clinical practice guidelines (CPGs) are available to inform practice decisions.

Objective

The aim of this study was to identify and systematically review the quality of existing ETS CPGs, specifically in the context of NSI and RM use.

Methods

A systematic search for ETS CPGs in children (<18 years old) was conducted in Cumulative Index to Nursing and Allied Health Literature, MEDLINE, PubMed, EMBASE, and Google Scholar. Two independent assessors evaluated CPGs using the Appraisal of Guidelines for Research and Evaluation II instrument. Standardised scores were calculated for individual CPGs, and scale domain scores were calculated.

Results

Four CPGs and practice recommendations from 2 literature reviews were identified and evaluated. The routine use of NSI and RMs with paediatric ETS was not recommended. Recommendations reflected the low quality and limited availability of evidence to inform NSI and RM application. Collectively, the highest scoring domain was clarity of presentation, followed by scope and purpose (78). Overall assessments ranged from 8 to 100 from a possible 100 points. Four ETS CPGs (100%) were recommended for use with modification.

Conclusions

Clinical practice guidelines and practice recommendations pertaining to NSI and RM were consistent but, however, limited by the quality and volume of available evidence. Clinical practice guideline developers should focus on improving the applicability and rigour in development processes. Further consensus work and rigorous trials are needed to inform future CPGs.
Development and Validation of a New Domestic Software for Dose Assessment during Normal and Accident Conditions in Nuclear Power Plants (NPPS)
Authors: Shad Ali Haghighi , Masti Darioush , Allaf Mitra Athari , Sepanloo Kamran , Hossein Feghhi Seyed Amir
Published: September 2020

In this research, a comprehensive code called KIANA is developed based on the Gaussian plume model to simulate and predict the radiological consequences received through all the possible, reasonable, probable, and standard exposure pathways for NPPs and chemical facilities. To validate the KIANA code, a case study is modeled for Bushehr Nuclear Power Plant Unit One (BNPP-1), and the KIANA code results are compared with the results of the Final Safety Analysis Report (FSAR-2017) data of BNPP-1. To assess the performance of the KIANA code, the total dose due to the airborne pathway in accident conditions including small break LOCA (SBLOCA), large break LOCA (LBLOCA), and equivalent exposure dose for the thyroid gland of a group of infants and children age 1 to 8 y at BNPP-1, are investigated. The KIANA code results show that the total effective doses do not exceed the regulatory limit of 5 mSv for external and internal exposures and the regulatory limit of 50 mSv for thyroid equivalent dose. The KIANA code results indicate good agreement with the results of FSAR-2017.
Prosthetic Valve Endocarditis Diagnosed Because of Persistent Hemolytic Anemia After Salmonella Iliopsoas Abscess Treatment
Authors: Kitazawa Takatoshi , Yamamoto Ai , Nakayama Shin , Misu Keita , Wakabayashi Yoshitaka , Yoshino Yusuke
Published: September 2020

Extraintestinal salmonellosis including infective endocarditis can cause serious complications. We present a case of prosthetic mitral valve endocarditis diagnosed because of hemolytic anemia after treatment of iliopsoas abscess and bacteremia caused by Salmonella Enteritidis. We also present a review of nontyphoidal Salmonella endocarditis. Prosthetic valve endocarditis cases had similar prognosis to native valve endocarditis cases, but they required surgery frequently. In a case of Salmonella bacteremia with prosthetic valves, infective endocarditis should be ruled out.
Quality of Life and Prolonged Symptoms in Korean Breast Cancer Survivors
Authors: Jang Min Kyeong , Kim Sue , Park Chang Gi , Collins Eileen G. , Quinn Lauretta T. , Ferrans Carol Estwing
Published: September 2020

Background

A culture of serious overwork in South Korea, more than other developed countries, may impact symptoms and quality of life (QOL) experienced by Korean breast cancer survivors (BCS).

Objectives

The aim of this study was to examine health-related QOL and influencing factors in BCS in Seoul, Korea, who have recovered from treatment for at least 1 year and returned to normal life and work.

Methods

In a cross-sectional study, 199 BCS completed a self-administered questionnaire in Seoul, Korea.

Results

Mean QOL scores were lower than expected, with 49% of the variance explained by depressive symptoms, physical fatigability, cognitive impairment, and social support. Psychological distress was high (67.8%), along with anxiety (47.2%) and depressive symptoms (36.7%). Participants reported a high prevalence of physical fatigability (71.1%), sleeping an average of only 6 hours per night, with 58.9% reporting poor quality sleep.

Conclusions

Quality of life was lower in Korean BCS than comparable studies in the United States, although participants received care at a premiere medical center. Depressive symptoms and anxiety were common and did not taper off over the 5 years after diagnosis, unlike BCS elsewhere. Korean survivors experienced significant physical fatigability, much higher than reported in a US study of mixed male and female cancer survivors. Overwork was not a significant predictor of QOL, although 30% of employed women reported working 45 to 90 hours weekly.

Implications for Practice

Findings demonstrate the importance of continued efforts to mitigate these symptoms in clinical survivorship care, as well as future research, to provide avenues for improving QOL for BCS, particularly in Korea.
99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Schmidkonz Christian , Götz Theresa Ida , Atzinger Armin , Ritt Philipp , Prante Olaf , Kuwert Torsten , Bäuerle Tobias , Goebell Peter , Cordes Michael
Published: September 2020

Objective

This study aims to investigate the value of 99mTc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT).

Methods

A total of 125 patients with biochemical recurrence of prostate cancer underwent 99mTc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)–positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent 99mTc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels.

Results

Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent 99mTc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43–0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20–0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07–0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38–0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13–0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0–0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT.

Conclusions

The results of our study show that 99mTc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1.
Unusual Case of an Exophytic Leiomyoma of Rectum Mimicking Malignancy on 18F-FDG PET/CT
Authors: Li Chongjiao , Tian Yueli , Shen Ying , Wen Bing , He Yong
Published: September 2020

Rectal leiomyoma is an exceedingly rare benign lesion. We here report a case with extraluminal leiomyoma of the middle and lower parts of the rectum showing aberrant hypermetabolism on 18F-FDG PET/CT in a 54-year-old man.
Isolated Pancreatic Metastasis From Choroidal Melanoma After 10 Years of Enucleation Mimicking Neuroendocine Tumor on 68Ga-DOTANOC PET/CT
Authors: Shamim Shamim Ahmed , Tripathy Sarthak , Rastogi Sameer , Barwad Adarsh , Prakash Sneha
Published: September 2020

Isolated pancreatic metastasis from choroidal melanoma is a rare phenomenon. We describe a case of a 38-year-old woman who underwent enucleation surgery for right choroidal melanoma and subsequently developed lesions in the pancreas 10 years after enucleation, which were depicted on 68Ga-DOTANOC PET/CT and confirmed to be metastasis from choroidal melanoma on surgical histopathology.
Pseudoprogression on 68Ga–Prostate-Specific Membrane Antigen-11 PET/CT in a Treated Glioblastoma
Authors: Gupta Manoj , Choudhury Partha Sarathi , Gairola Munish , Premsagar Ishwar Chandra , Rao Sriram Avinash
Published: September 2020

After standard treatment of glioblastoma, pseudoprogression versus true progression is a clinical challenge. Indeed, to differentiate these 2 on contrast MRI (cMRI) is problematic. In recent time, 68Ga–prostate-specific membrane antigen-11 (68Ga-PSMA) PET/CT has been suggested to have high accuracy in glioblastoma recurrence. We present a case of a 40-year-old man with right frontotemporal glioblastoma underwent surgery and radiotherapy. One month posttreatment cMRI showed a new enhancing lesion in the right hippocampal region, which was also positive on 68Ga-PSMA-11 PET/CT. On follow-up with conservative management, both cMRI and 68Ga-PSMA-11 PET/CT showed regression in new lesion, hence suggest pseudoprogression.
10-Year Clinical Experience With 18F-Choline PET/CT
Authors: Zattoni Fabio , Ravelli Ilaria , Rensi Marco , Capobianco Decio , Borsatti Eugenio , Baresic Tania , Chiaravalloti Agostino , Schillaci Orazio , Alongi Pierpaolo , Bartolotta Tommaso Vincenzo , Rambaldi Ilaria , Bartolomei Mirco , Farsad Mohsen , Tredici Manuel , Donner Davide , Chierichetti Franca , Trifirò Giuseppe , Brugola Elisabetta , Burei Marta , Dal Moro Fabrizio , Cecchin Diego , Evangelista Laura
Published: September 2020

Purpose

The primary aim of this multicenter retrospective analysis is to examine the role of 18F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive 18F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences.

Materials and Methods

This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent 18F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning.

Results

18F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008–2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan.

Conclusions

18F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of 18F-choline images and in patient selection in the last 5 years.
Widespread Skin Infiltration of Leukemia Cutis on 18F-FDG PET/CT
Authors: Zheng Jieling , Xue Qianqian , Lin Kaixian , Miao Weibing
Published: September 2020

A 67-year-old man experienced multiple cutaneous nodules for 3 weeks. His initial skin biopsy only showed local inflammation. However, after a 2-week anti-inflammation therapy, the skin manifestations were not improved while the leukocyte count gradually increased. FDG PET/CT revealed widespread cutaneous and subcutaneous hypermetabolic lesions in many parts of the body, and heterogeneously increased uptakes in the bone marrow. Bone marrow biopsy and second skin biopsy were performed. Pathological examination from both specimen demonstrated acute monocytic leukemia.
18F-Fluciclovine PET/MRI in a Patient With Squamous Cell Carcinoma of the Uterine Cervix Correlated With 18F-FDG PET/CT
Authors: Nguyen Nghi C. , Moon Chan Hong , Beriwal Sushil
Published: September 2020

A 32-year-old woman with a FIGO (International Federation of Gynecology and Obstetrics) stage IIA invasive squamous cell carcinoma of the uterine cervix underwent a clinical FDG PET/CT scan, which revealed intense uptake in the primary. On research 18F-fluciclovine PET/MRI, the primary showed elevated fluciclovine uptake at 5 and 40 minutes after radiotracer injection, with no evidence of regional or distant metastasis. Fluciclovine PET may have diagnostic value for cervical cancer imaging with a potential advantage over FDG of minimal urinary activity from renal excretion; however, in this patient, the metabolic activity was inferior to that of FDG PET.
FDG PET/CT Suggesting Pulmonary Artery Involvement of Takayasu Arteritis
Authors: Liu Yong , Tong Guansheng , Wen Zhe
Published: September 2020

Pulmonary artery involvement can occur in about half of the patients suffering Takayasu arteritis. Increased FDG activity in the aorta and its main branches in patients with Takayasu arteritis on PET/CT had been well-reported. However, the FDG PET/CT appearance of pulmonary artery involvement in Takayasu arteritis is less known. We present FDG PET/CT findings in a 37-year-old patient with known Takayasu arteritis. The images showed rim-like FDG activity in opacities in the left lung, which was later proven due to narrowed left main pulmonary artery.
18F-FDG PET/CT in Xanthoma Disseminatum
Authors: Arslan Esra , Aksoy Tamer , Leblebici Cem , Koku-Aksu Ayşe Esra , Çermik Tevfik Fikret
Published: September 2020

A 64-year-old woman who had yellowish orange–colored, sharp-edged, and flat skin plaques and back pain for about a year was referred for 18F-FDG PET/CT imaging and her bone marrow biopsy revealed 10% to 20% atypical plasma cells suggestive of monoclonal gammopathy. PET/CT showed linear 18F-FDG uptake on the surface of the skin on the neck, axillary, chest, inframammary, and inguinal regions. Punch biopsy revealed numerous histiocyte infiltrates with large vacuoles, xanthomized cytoplasm in the dermis, and midsection, and there are several Touton-type giant cells supporting the preliminary diagnosis of xanthoma disseminatum.
99mTc-MDP Bone Scan Findings in Fibrodysplasia Ossificans Progressiva
Authors: Gupta Nitin , Verma Ritu , Belho Ethel Shangne , Dey Sudip
Published: September 2020

Fibrodysplasia ossificans progressiva is a rare debilitating, connective tissue disease characterized by progressive extraosseous ossification with abnormal great toes. Clinical (hallux valgus), radiological, and classical bone scan findings help to reach diagnosis and prevent patient from unnecessary surgical interventions for fibrodysplasia ossificans progressiva lesions and radiotherapy cycles. Here we present a case where a child presented with multiple swellings over the body and hallux valgus, and further bone scan findings helped to reach the diagnosis. The progressive nature of disease is difficult to halt, but early diagnosis can help in the delay of the disease process, by preventing trauma and giving disease-modifying agents.
Incidental COVID-19 Pneumonia on 18F-Fluorocholine PET/CT
Authors: García Vicente Ana María , Soriano Castrejón Ángel
Published: September 2020

We present the case of a patient who underwent 18F-fluorocholine PET/CT for biochemical recurrence of prostate cancer in which bilateral pneumonia was diagnosed. In the current state of COVID-19 pandemic, a high prevalence of incidental pneumonia may be expected, even with previous clinical triage, explained by a nondefined number of patients who were asymptomatic or minimally symptomatic for infectious process. Therefore, nuclear medicine physicians should be prepared to recognize and diagnose incidental COVID-19 pneumonia manifestation on 18F-fluorocholine PET/CT, due to the crucial epidemiological implications.
Head-to-Head Comparison of the Two MAO-B Radioligands, 18F-THK5351 and 11C-L-Deprenyl, to Visualize Astrogliosis in Patients With Neurological Disorders
Authors: Ishibashi Kenji , Kameyama Masashi , Miura Yoshiharu , Toyohara Jun , Ishii Kenji
Published: September 2020

Three patients with neurological disorders (cerebral infarction, progressive multifocal leukoencephalopathy, and multiple sclerosis) underwent 18F-THK5351 and 11C-L-deprenyl PET on the same day to visualize lesions undergoing astrogliosis by measuring MAO-B activity. BP
ND map and SUV image with 18F-THK5351 as well as K
i map, K
i/K
1 map and SUV image with 11C-L-deprenyl were created. 18F-THK5351 BP
ND maps and SUV images clearly identified the lesions undergoing astrogliosis. 11C-L-deprenyl K
i/K
1 maps were close to 18F-THK5351 images, but very noisy. K
i maps and SUV images were likely affected by the effect of blood flow. Hence, 18F-THK5351 is superior to 11C-L-deprenyl for visualizing lesions undergoing astrogliosis.
18F-FDG PET/CT in Labrune Syndrome
Authors: Cuzzocrea Marco , Florimonte Luigia , Scola Elisa , Benti Riccardo , Castellani Massimo
Published: September 2020

A 69-year-old woman presented with cognitive impairment related to attentive, executive, and mnemonic functions; progressive worsening of walking, speaking, writing, and reading ability; and double sphincter incontinence. Leukoencephalopathy, cystic lesions, and calcifications, suspected for Labrune syndrome, were observed at MRI and CT brain images. Generalized wave abnormalities were also visible at electroencephalogram. Functional brain imaging performed with 18F-FDG PET/CT demonstrated a decreased glucose metabolism in impaired brain regions, in accordance with MRI findings. Genetic testing confirmed a mutation of SNORD118.
Successful and Safe Treatment With 177Lu-DOTATATE (Lutathera) of Progressive Metastatic Pancreatic Neuroendocrine Tumor Under Hemodialysis
Authors: Dierickx Lawrence O. , Séverine Brillouet , Fatima Mokrane , Amel Bensafi , Rosine Guimbaud
Published: September 2020

177Lu-DOTATATE is an effective treatment for inoperable metastatic well-differentiated pancreatic neuroendocrine tumors. There are no guidelines for patients with terminal renal failure. We present the case of a 74-year-old woman who received different lines of treatment: analogs of somatostatin, chemotherapy, a first series of peptide receptor radionuclide therapy (PRRT), and finally chemoembolization. Because of persistent hepatic progression, a safe and successful administration of 4 cycles of a second series of PRRT under hemodialysis was administered. Patient was in scintigraphic complete remission at 12 months with normal hematological parameters at 12 and 30 months after PRRT.