Designing a new molecular probe : the potential role for Tilmanocept (Lymphoseek) in the assessment of patients with painful hip and knee joint prostheses

There is a long history of nuclear medicine developments in orthopaedics beginning in the early 20th century. Technetium-99m (99mTc) has a short half-life of six hours, emits 140 keV gamma rays and is the most widely used isotope, imaged with the Anger (gamma) camera. Gamma image quality and test sensitivity in painful prosthetic joints can be improved with single photon emission computed tomography (SPECT) and SPECT/CT. Positron Emission Tomography-Computed Tomography (PET-CT) with Sodium Fluoride (18F-NaF) and 18Fluorine-fluorodeoxyglucose (18F-FDG) PET have promising and limited roles respectively in the investigation of painful prosthetic joints. New SPECT/CT and PET-CT isotopes targeting activated macrophages with 99mTc Tilmanocept (Lymphoseek®) and 68Gallium labelled Tilmanocept respectively show potential as agents to demonstrate wear particles ingested by macrophages and multinucleated giant cells. An imaging algorithm using SPECT and/or PET agents is proffered as a cost effective way of speedily and accurately arriving a diagnosis. Methods: Review of the historical role of nuclear medicine in orthopaedics and research into the potential role of new radiopharmaceutical agents was undertaken. Guidelines and algorithms for the imaging of complicated joint prosthesis are provided. Results: There is an established role for nuclear medicine in orthopaedics and particularly in the investigation of complicated joint prostheses. Imaging with Tilmanocept provides new opportunities to shorten the time to diagnose loosened and infected joint prostheses. Conclusion: There is a potential new role for Tilmanocept, which can be utilised with both PET-CT and SPECT-CT technologies. Tilmanocept is a relatively new radiopharmaceutical which has a potential role in the imaging assessment of painful joint prosthesis

The promising role of dynamic 18F-NaF PET-CT in diagnosing symptomatic joint prosthesis

Our purpose was to establish proof of principle case study for the use of dynamic 18F-NaF PET-CT in the assessment of knee and hip prostheses. Approval was granted by the research ethics committee and informed consent was obtained. This is a case study investigating the role of dynamic 18F NaF PET-CT in a patient with bilateral knee prostheses (1 symptomatic/painful and 1 asymptomatic). Both knees were studied with dynamic 18F-NaF PET-CT technique to demonstrate the different pattern of uptake in normal/asymptomatic joint as well as painful joints with aseptic loosening. In addition, a knee aspirate was obtained from the symptomatic knee and serum C-reactive protein and erythrocyte sediment rate levels as well as a peripheral white cell count were obtained in addition to 12 month clinical follow up. Images were obtained with multi-sequential dynamic image acquisition in list mode using GE Healthcare® volume imaging protocol (ViP) after an intravenous injection of 250 MBq 18F-NaF. The images were interpreted as normal, loosening or septic loosening based on the graphical pattern of tracer uptake produced at the bone-prosthesis interface. A final diagnosis was made by a combination of joint aspiration microbiology and clinical follow-up for 1 year; in addition to C-reactive protein and erythrocyte sediment rate levels as well as peripheral white cell count. NaF PET results were compared with 3-phase dynamic bone scan results and plain radiographs. The degree of uptake in the symptomatic joint exceeded background levels and also levels of uptake in the asymptomatic knee. The pattern of uptake and curve slope in both the asymptomatic and symptomatic joints matched the pattern of uptake in our hypothesis. Dynamic 18F-NaF PET-CT is a useful imaging modality for assessing painful joint prosthesis. It can differentiate between asymptomatic joints and aseptic loosening. However, more work is required for the detection of septic loosening

Epidemiological studies of the incidence of pathogenic Campylobacter spp. amongst animals in Lagos metropolis

Faecal specimens were collected from different animal species (puppies, Guinea fowl, chicken and pigs) at different farm locations in Lagos (Inner City - Central urban area; peripheral City – rural/farminghouses; Rural - a farming and agricultural zone, where people raised their own domestic animals). In all, 200 animals were sampled out of which twenty (14%) were positive for Campylobacter, seventeen (17)of these (60.7) were positive for animals from peripheral zone, nine (9)(32.1%) were found positive for animals from the rural zone and two (2)(7.1%) were positive for animals obtained from the inner zone ofLagos metropolis. The trend of infection by Campylobacter as exemplified in this study was pig, two samples (7.1%); chicken, 7 samples (25%); sheep, two samples (7.1%); puppies, 0 (0.0%), and guinea fowl, 17 samples (60.7). The peripheral zone had more incidence of Campylobacter with an incidence rate in the order peripheral zone (8.5%» rural zone (4.5%) > inner zone (1.0%). The results ofbiochemical tests reveal that three (3) samples were positive for Campylobacter coli biotype II, seventeen (17) samples were positive for Campylobacter coli biotype I and one (1) sample for Campylobacter jejuni biotype I. These results are indicative that the epidemic of Campylobacter infection is possible amongst handlers of these farm animals

Normal CD4, CD8 T-lymphocytes and leucocyte baseline in healthy HIV-seronegative pregnant women in Ekpoma, Edo State, Nigeria

This study was aimed at establishing the baseline values of CD4 and CD8 absolute counts among healthy pregnant women in Ekpoma, Edo State, Nigeria. Ninety (90) apparently healthy pregnant women between the age group of 18-39 years and thirty (30) non- pregnant women (control) were used as study subjects. The pregnant subjects were divided into three groups, depending on the trimester of pregnancy. CD4 and CD8 absolute counts were determined using flow cytometry. An automated blood analyzer was used to determine the leucocyte counts. The mean WBC (total) count (x103/μl) of the pregnant women was 7.71±1.76 against 4.97 ± 0.82 of the control subjects. Statistical comparison showed a statistical significance changes in the mean CD4 counts between the test and control subjects but no statistical significant difference in the total WBC and absolute CD8 counts of both groups (P>0.05). In contrast, the CD4 absolute count showed a statistical significant difference when compared with the mean values of the control subjects. In conclusion, pregnancy significantly increased the mean values of WBC count but significantly decreased CD4+ cell count when compared to nonpregnant controls while the mean CD8+ cell count did not show any difference in the subjects studied.Key words: CD4 counts, CD8 counts, Leucocytes counts, Healthy pregnant women, Ekpom

Brown fat depots in adult humans remain static in their locations on PET/CT despite changes in seasonality

Active brown adipose tissue (BAT) in humans has been demonstrated through use of positron emission tomography with 2-deoxy-2-(fluorine-18) fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) scans. The aim of our study was to determine whether active human BAT depots shown on 18F-FDG PET/CT scans remain static in their location over time. This was a retrospective study. Adult human subjects (n = 15) who had had 18F-FDG PET/CT imaging (n = 38 scans in total) for clinical reasons were included on the basis of 18F-FDG uptake patterns consistent with BAT activity. For each subject, 18F-FDG BAT uptake pattern on serial 18F-FDG PET/CT images was compared to an index 18F-FDG PET/CT image with the largest demonstrable BAT volume. Object-based colocalization was expressed as Mander's correlation coefficient (where 1 = 100% overlap, 0 = no overlap). Distribution of 18F-FDG BAT activity over time and across multiple 18F-FDG BAT scans was equivalent in 60% (n = 9) of the subjects. The degree of consistency in the pattern of 18F-FDG BAT uptake in each subject over time was greater than expected by chance in 87% (n = 13) of the subjects (pair-wise agreement 75–100%, Fleiss’ κ 0.4–1). The degree of BAT colocalization on serial scans was greater than that expected by chance in 93% (n = 14) of the subjects (mean Mander's coefficient 0.81 ± 0.21 [95% CI]). To our knowledge, our study provides the most conclusive evidence to date to support the notion that active BAT depots in humans (volumes and activities of which were measured through use of 18F-FDG PET/CT scans) remain static in location over sustained periods

Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK

BACKGROUND: Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. METHODS: We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). RESULTS: We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. CONCLUSIONS: Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management

The JAX Synteny Browser for mouse-human comparative genomics.

Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an interactive web-based conserved synteny browser, The Jackson Laboratory (JAX) Synteny Browser. The browser allows researchers to highlight or selectively display genome features in the reference and/or the comparison genome according to the biological attributes of the features. Although the current implementation for the browser is limited to the reference genomes for the laboratory mouse and human, the software platform is intentionally genome agnostic. The JAX Synteny Browser software can be deployed for any two genomes where genome coordinates for syntenic blocks are defined and for which biological attributes of the features in one or both genomes are available in widely used standard bioinformatics file formats. The JAX Synteny Browser is available at: http://syntenybrowser.jax.org/. The code base is available from GitHub: https://github.com/TheJacksonLaboratory/syntenybrowser and is distributed under the Creative Commons Attribution license (CC BY)

Factors associated with depression, anxiety, and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis

Background: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness. However, factors associated with mental illness are unclear. / Objectives: To synthesise and evaluate all available evidence on factors associated with depression, anxiety, and severe mental illness (SMI) among adults with AE or psoriasis. / Methods: We searched electronic databases, grey literature databases, and clinical trial registries from inception to February 2022 for studies in adults with AE or psoriasis. Eligible studies were randomised controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety, or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesised results narratively, and if at least two studies were sufficiently homogenous, we pooled effect estimates in a random-effects meta-analysis. / Results: We included 21 studies (11 observational, 10 RCT). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest being female, and psoriatic arthritis, were associated with depression (female sex:OR = 1.62,95%CI = 1.09-2.40,95%PI = 0.62-4.23, I2 = 24.90%, Tau2 = 0.05; psoriatic arthritis:OR = 2.26,95%CI = 1.56-3.25,95%PI = 0.21-24.23, I2 = 0.00%, Tau2 = 0.00) and anxiety (female sex:OR = 2.59,95%CI = 1.32-5.07,95%PI = 0.00-3956.27, I2 = 61.90%, Tau2 = 0.22; psoriatic arthritis:OR = 1.98,95%CI = 1.33-2.94, I2 = 0.00%, Tau2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR = 1.14,95%CI = 1.05-1.25, I2 = 0.00%, Tau2 = 0.00), but not depression. Evidence from RCTs suggested adults with AE or psoriasis given placebo had higher depression and anxiety scores compared to comparators given targeted treatment (e.g., biologic agents). / Conclusions: Our review highlights limited existing research on factors associated with depression, anxiety, and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared to skin disease treated with targeted therapy, however, follow-up was limited, therefore long-term effects on mental health are unclear

Long-term oral antibiotic use in people with acne vulgaris in UK primary care: a drug utilization study

BACKGROUND: The inappropriate use of antibiotics is understood to contribute to antimicrobial resistance. Oral antibiotics are regularly used to treat moderate-to-severe acne vulgaris. In practice, we do not know the typical length of oral antibiotic treatment courses for acne in routine primary care and what proportion of people receive more than one course of treatment following a new acne diagnosis. OBJECTIVES: To describe how oral antibiotics are prescribed for acne over time in UK primary care. METHODS: We conducted a descriptive longitudinal drug utilization study using routinely collected primary care data from the Clinical Practice Research Datalink GOLD (2004-2019). We included individuals (8-50 years) with a new acne diagnosis recorded between 1 January 2004 and 31 July 2019. RESULTS: We identified 217 410 people with a new acne diagnosis. The median age was 17 years [interquartile range (IQR) 15-25] and median follow-up was 4.3 years (IQR 1.9-7.6). Among people with a new acne diagnosis, 96 703 (44.5%) received 248 560 prescriptions for long-term oral antibiotics during a median follow-up of 5.3 years (IQR 2.8-8.5). The median number of continuous courses of antibiotic therapy (≥ 28 days) per person was four (IQR 2-6). The majority (n = 59 010, 61.0%) of first oral antibiotic prescriptions in those with a recorded acne diagnosis were between the ages of 12 and 18. Most (n = 71 544, 74.0%) first courses for oral antibiotics were for between 28 and 90 days. The median duration of the first course of treatment was 56 days (IQR 50-93 days) and 18 127 (18.7%) of prescriptions of ≥ 28 days were for < 6 weeks. Among people who received a first course of oral antibiotic for ≥ 28 days, 56 261 (58.2%) received a second course after a treatment gap of ≥ 28 days. The median time between first and second courses was 135 days (IQR 67-302). The cumulative duration of exposure to oral antibiotics during follow-up was 255 days (8.5 months). CONCLUSIONS: Further work is needed to understand the consequences of using antibiotics for shorter periods than recommended. Suboptimal treatment duration may result in reduced clinical effectiveness or repeated exposures, potentially contributing to antimicrobial resistance