Can 3D Camera Imaging Provide Improved Information to Assess and Manage Lymphoedema in Clinical Practice?

Background Accurate diagnosis and measurement of limb volume in people with lymphoedema is important in order to provide best information for treatment, management and self-management. Current assessment methods lack detail and accuracy. Three-dimensional camera imaging (3DCI) holds the potential to be cheap, accurate, and provide additional material about limb shape not provided by current methods. However, there is a need to ensure that this assessment method is valid and reliable. Methodology This prospective, observational, longitudinal study utilised a diagnostic test study framework to determine the validity, reliability and accuracy of 3DCI compared to circumferential tape measurement (CTM) and perometry and to explore whether shape is a feasible alternative to measure upper limb lymphoedema. Twenty women with breast cancer-related lymphoedema were recruited. Phase one assessed criterion validity, intra-rater reliability, and accuracy of 3DCI by measuring limb volume of each participant with CTM, perometry and 3DCI four times over six months. Phase two investigated the use of limb shape as a method of lymphoedema assessment using oedema maps and calculations of shape redundancy derived from the 3DCI images in phase one. These data sets were matched against limb volume to determine criterion validity, intra-rater reliability and accuracy. Results 3DCI had high intra-rater correlation (ICC=0.87; p<0.00). Concurrent validity ranged from 0.82 to 0.86 against perometry and CTM, with good sensitivity (91.7% to 100%) and moderate specificity (50% to 66.7%). Limb shape calculation (shape redundancy) had moderate intra-rater correlation (ICC=0.71; p=0.01); but correlated poorly with limb volume (r=0.19 to 0.39). Coloured oedema maps were sensitive to change over time with colours clearly identifying problem areas and fluctuations within the affected limb. Conclusion Our study shows that 3DCI is a reliable, valid and accurate method of limb volume measurement, and that it could provide supportive information in clinical assessment. In addition, limb shape provides insight into localised areas of swelling, which other methods of lymphoedema measurement do not. However, shape redundancy requires further refinement

Correlates of Fatigue in Patients With Heart Failure

This study was conducted to determine the prevalence of fatigue and identify its demographic, clinical, and psychological correlates in 150 heart failure (HF) patients (73% men, 66% Caucasian, mean age 55 years, mean ejection fraction 26.7%±11%), from a single HF center, using the Profile of Mood States-Fatigue Subscale, the Minnesota Living With Heart Failure Questionnaire, and the Beck Depression Inventory. Sociodemographic and clinical data were obtained through self-report and chart abstraction. High levels of fatigue were reported in 50.4% of men and 51.2% of women. In a multivariate model, maximal workload, physical health, emotional health, and depression explained 51% of the variance in fatigue (P<.001). Fatigue in patients with HF is associated with both clinical and psychosocial variables, offering a number of targets for intervention. These findings suggest the need for multiple risk factor intervention strategies that improve physical and emotional health to decrease fatigue. Patients with depression warrant particular scrutiny

Guidelines for managing people with lymphoedema remotely: a post-COVID-19 response document

During the COVID-19 pandemic it was initially not possible to see people with lymphoedema face-to-face at lymphoedema services, due to the potential risks of the virus, because they were shielding, because of redeployment of rooms or staff, and due to sporadic restrictions of movement. The pandemic therefore accelerated adjustments in lymphoedema service delivery, while ensuring effective and efficient care was paramount. This document presents a pragmatic guide for lymphoedema services. Although clinical and non-clinical staff need to comply with guidance from their own organisations/commissioners, this document aims to provide specific guidance and share good practice in relation to lymphoedema management. These guidelines are based on analysis of the national response of Lymphoedema Network Wales during the first few months of the COVID-19 pandemic and incorporate supporting contemporary advice. They have been used throughout NHS Wales, providing a standardised approach in supporting care for people with lymphoedema. In light of the enduring nature of COVID-19, it is imperative that lymphoedema services have a means to provide suitable care for patients. Although face-to-face appointments are sometimes deemed necessary, many patients can be suitably supported via telehealth consultations. These guidelines may help lymphoedema services restore and reset in a safe and acceptable manner

Human Biodistribution and Dosimetry of 11C-CUMI-101, an Agonist Radioligand for Serotonin-1A Receptors in Brain

As a reported agonist,11C-CUMI-101 is believed to selectively bind the G-protein-coupled state of the serotonin-1A (5-HT1A) receptor, thereby providing a measure of the active subset of all 5-HT1A receptors in brain. Although 11C-CUMI-101 has been successfully used to quantify 5-HT1A receptors in human and monkey brain, its radiation exposure has not previously been reported. The purpose of this study was to calculate the radiation exposure to organs of the body based on serial whole-body imaging with positron emission tomography (PET) in human subjects

Exploring the impact of lymphoedema on individuals and if lymphatic venous anastomosis surgery effects perceptions on quality of life: A qualitative study

Purpose: Lymphoedema is a chronic condition, a cancer consequence and causes physical, psychological, and social implications. A new super-micro surgical treatment Lymphatic Venous Anastomosis (LVA) may improve the symptoms of lymphoedema. This study aims to explore the impact of lymphoedema on individuals and if LVA Surgery changes perceptions on quality of life. Method: Semi-structured interviews were conducted with sixteen individual's pre-LVA surgery and repeated six months later post-LVA with ten of the participants. Transcripts were analysed using thematic analysis. Results: Themes identified pre-LVA included: Impact of Living with Lymphoedema, Being Different, and Future Hopes and Emotions. Participants reported making significant changes to ‘normal' life due to living with lymphoedema. Changes included alteration in shopping, cleaning, hobbies, familial roles, employment and sexual intimacy. The wearing of compression garments engendered feelings of being unattractive. Themes found post-LVA were: I am one of the Lucky Ones and Returning to Former Self. Post-LVA, participants described how life had become more normalised with fear and apprehension of developing cellulitis reduced. Positive changes had enabled usual activities of daily living to recommence. Some participants had decreased pain, aching, heaviness, stiffness and were wearing their compression garments less. Conclusion: The findings suggest that the real impact of living with lymphoedema is much more challenging than previously identified. The findings suggest that LVA can give a future of greater choice for some of its recipients, but further research should explore longer-term benefits. LVA could offer hope to some people with lymphoedema, but a realistic expectation is essential

Audit to strategy: development of a national children and young people lymphoedema service

Lymphoedema in children and young people (CYP) can cause significant impact affecting physical, psychological and social wellbeing. This audit of 286 CYP with Lymphoedema (2015–2018) is the first national cohort reported and provides new information on patient reported outcome (PROM) changes over time. Conservative therapy produced statistically significant change in outcome measures relating to swelling, infection, appearance and compression garments. Almost half of the children had primary lymphoedema of varying types. An overall prevalence of 31 per 100 000 CYP with lymphoedema was found among a population aged 0–25 over a 3-year period. This finding suggests a higher occurrence of lymphoedema in children and young people than previously reported and is important for service planning and health professionals' education

Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer’s disease and controls

BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity

Development of a non-radiometric method for measuring the arterial input function of a C-11-labeled PET radiotracer

Positron emission tomography (PET) uses radiotracers to quantify important biochemical parameters in human subjects. A radiotracer arterial input function (AIF) is often essential for converting brain PET data into robust output measures. For radiotracers labeled with carbon-11 (t(1/2)=20.4 min), AIF is routinely determined with radio-HPLC of blood sampled frequently during the PET experiment. There has been no alternative to this logistically demanding method, neither for regular use nor validation. A C-11-labeled tracer is always accompanied by a large excess of non-radioactive tracer known as carrier. In principle, AIF might be obtained by measuring the molar activity (A(m); ratio of radioactivity to total mass; Bq/mol) of a radiotracer dose and the time-course of carrier concentration in plasma after radiotracer injection. Here, we implement this principle in a new method for determining AIF, as shown by using [C-11]PBR28 as a representative tracer. The method uses liquid chromatography-tandem mass spectrometry for measuring radiotracer A(m) and then the carrier in plasma sampled regularly over the course of a PET experiment. A(m) and AIF were determined radiometrically for comparison. The new non-radiometric method is not constrained by the short half-life of carbon-11 and is an attractive alternative to conventional AIF measurement

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-α-aminoadipic semialdehyde/l-Δ1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine l-α-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary l-α-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenario