The definitions, assessment, and dimensions of cancer-related fatigue: A scoping review.

PURPOSE: Cancer-related fatigue (CRF) is challenging to diagnose and manage due to a lack of consensus on its definition and assessment. The objective of this scoping review is to summarize how CRF has been defined and assessed in adult patients with cancer worldwide. METHODS: Four databases (PubMed, Embase, CINAHL Plus, PsycNet) were searched to identify eligible original research articles published in English over a 10-year span (2010-2020); CRF was required to be a primary outcome and described as a dimensional construct. Each review phase was piloted: title and abstract screening, full-text screening, and data extraction. Then, two independent reviewers participated in each review phase, and discrepancies were resolved by a third party. RESULTS: 2923 articles were screened, and 150 were included. Only 68% of articles provided a definition for CRF, of which 90% described CRF as a multidimensional construct, and 41% were identical to the National Comprehensive Cancer Network definition. Studies were primarily conducted in the United States (19%) and the majority employed longitudinal (67%), quantitative (93%), and observational (57%) study designs with sample sizes ≥ 100 people (57%). Participant age and race were often not reported (31% and 82%, respectively). The most common cancer diagnosis and treatment were breast cancer (79%) and chemotherapy (80%; n = 86), respectively. CRF measures were predominantly multidimensional (97%, n = 139), with the Multidimensional Fatigue Inventory (MFI-20) (26%) as the most common CRF measure and "Physical" (76%) as the most common CRF dimension. CONCLUSION: This review confirms the need for a universally agreed-upon definition and standardized assessment battery for CRF.

A mosaic activating mutation in AKT1 associated with the Proteus syndrome.

BACKGROUND: The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS: We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS: Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS: The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.).

Defining fatigue from the experiences of patients living with chronic fatigue.

Introduction: Fatigue is a multidimensional, highly individualized symptom experience perceived by people, regardless of health status. It is the most common complaint among those seeking primary care, yet, despite being a frequently reported symptom, it remains poorly understood. Methods: This is an exploratory study utilizing a qualitative descriptive approach that aims to explore the description of fatigue from the personal experiences of 16 participants living with chronic fatigue. Themes were generated from transcripts of in-depth interviews that focused on a central question: "how would you describe your fatigue from your own experience?" Results: Analysis of the participants' interview transcripts revealed three themes. The first theme focused on fatigue as a unique personal experience, which included experiential descriptions or measures of fatigue that the participants used to describe their symptoms. The second theme focused on fatigue as an experience beyond self, which highlighted the consequences of fatigue on interpersonal interactions and the performance of social roles, as well as the potential of utilizing social support to cope with the limitations caused by this condition. The last theme was on living with fatigue, which focused on ways participants attempted to discern their condition and manage the consequences of fatigue. Discussion: Experiences of chronic fatigue have patterns and personal meanings that vary between individuals. Caring for persons experiencing chronic fatigue requires acknowledgment of unique personal experiences and coping strategies. Due to the nature of the method, the results of this study are not generalizable and only reflect the experiences of the participants.

Self-reporting of psychoneurophysical (PNP) symptoms in adults with four chronic diseases: a protocol for a scoping review.

BACKGROUND: Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual's unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath. METHODS: Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records' title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses. DISCUSSION: This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw.

Cognitive, sensory, and psychosocial characteristics in patients with Bardet-Biedl syndrome.

Forty-two patients with a clinical diagnosis of Bardet-Biedl syndrome ages 2-61 years were given a neuropsychological test battery to evaluate cognitive, sensory, and behavioral functioning. These tests included the Wechsler scales of intelligence, Rey Auditory Verbal Learning Test, Boston Naming Test, D-KEFS Verbal Fluency Test, D-KEFS Color-Word Interference Test, D-KEFS Sorting Test, Wide Range Achievement Test: Math and Reading Subtests, Purdue Pegboard, The University of Pennsylvania Smell Identification Test, Social Communication Questionnaire, Social Responsiveness Scale, and Behavior Assessment System for Children, Second Edition, Parent Rating Scale. On the age appropriate Wechsler scale, the mean Verbal Comprehension was 81 (n = 36), Working Memory was 81 (n = 36), Perceptual Reasoning was 78 (n = 24) and Full Scale IQ was 75 (n = 26). Memory for a word list (Rey Auditory Verbal Learning Test) was in the average range with a mean of 89 (n = 19). Fine motor speed was slow on the Purdue with mean scores 3-4 standard deviations below norms. All subjects were microsmic on the University of Pennsylvania Smell Identification Test. Of these 42 patients, only 6 were able to complete all auditory and visual tests; 52% were unable to complete the visual tests due to impaired vision. A wide range of behavioral issues were endorsed on questionnaires given to parents. Most had social skill deficits but no pattern of either externalizing or internalizing problems. We identify a characteristic neuro-behavioral profile in our cohort comprised of reduced IQ, impaired fine-motor function, and decreased olfaction.

Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS).

BACKGROUND: Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. METHODS: A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. RESULTS: All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. CONCLUSIONS: There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients with BBS, which parallel the findings, described in BBS mutant mouse models. Some of these brain abnormalities may be progressive and associated with the reported neurological and behavioral problems. Further future correlation of these MRI scan findings with detailed neurologic and neuropsychological exams together with genotype data will provide better understanding of the pathophysiology of BBS.