Investigating the feasibility of a hand-held photoacoustic imaging probe for margin assessment during breast conserving surgery.

Approximately 19 % of breast cancer patients undergoing breast conserving surgery (BCS) must return for a secondary surgery due to incomplete tumour removal. Our previous work demonstrated that the lower lipid content, characteristic of tumour tissue, was observed as regions of hypo-intense photoacoustic (PA) contrast. The goal of this work was to evaluate feasibility of a low-frequency, hand-held PA imaging probe for surgical margin assessment based on lipid content differences. Here, we describe (i) the design of a prototype hand-held PA imaging probe, (ii) the effect of limited-bandwidth on image contrast, (iii) accuracy towards hypo-intense contrast detection, (iv) the limited-view characteristics of the single sensor design, and (iv) early imaging results of an ex-vivo breast cancer specimen. The probe incorporates a single polyvinylidene fluoride acoustic sensor, a 1-to-4 optical fibre bundle and a polycarbonate axicon lens for light delivery. Imaging results on phantoms designed to mimic positive margins demonstrated the ability to detect gaps in optical absorption as small as 1 mm in width. Compared to images from a near full-view PAI system, the hand-held PAI probe had higher signal to noise ratio but suffered from negativity image artifacts. Lumpectomy specimen imaging showed that strong signals can be obtained from the fatty tissue. Taken together, the results show this imaging approach with a hand-held probe has potential for detection of residual breast cancer tissue during BCS; however, more work is needed to reduce the size of the probe to fit within the surgical cavity.

PATLAB: A graphical computational software package for photoacoustic computed tomography research.

Photoacoustic tomography (PAT) provides high resolution optical images of tissue at depths of up to several centimetres. This modality has been of interest to researchers for at least 30 years and is still the subject of intensive research. However, PAT researchers lack access to a comprehensive open-source graphical simulation and reconstruction software package. In this article, we introduce PATLAB, an open-source MATLAB-based graphical software package that can perform both PAT simulation and image reconstruction. PATLAB is simple to use yet is capable of complex PAT data processing tasks and offers advanced users a framework to build and test new methods.

Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes - an observational cross-sectional study.

BACKGROUND: To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability. METHODS: A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated. RESULTS: A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761-1.000) compared to Swept Source (0.113-0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source. CONCLUSIONS: AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.

Folliculitis decalvans and lichen planopilaris phenotypic spectrum: a case series of biphasic clinical presentation and theories on pathogenesis.

We present a series of 13 patients with clinical and histological features of both folliculitis decalvans (FD) and lichen planopilaris (LPP), either concomitantly, or sequentially as the clinical phenotype changed over time. This biphasic presentation of FD-LPP is not as uncommon as would be expected from the lack of description in the literature. We discuss current theories about the pathogenesis of both LPP and FD, and speculate how abnormal immune responses may either predispose to secondary bacterial infection or be influenced by dysbiosis of the skin/hair follicle microbiome, resulting in inflammation and permanent hair follicle damage.

Meta-analysis of clinical trials examining the benefit of structured home exercise in patients with peripheral artery disease.

BACKGROUND: Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme. METHODS: A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences. RESULTS: Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50; P < 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62; P < 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47; P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43; P = 0·001). CONCLUSION: This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

Risk of major amputation in patients with intermittent claudication undergoing early revascularization.

BACKGROUND: Revascularization is being used increasingly for the treatment of intermittent claudication and yet few studies have reported the long-term outcomes of this strategy. The aim of this study was to compare the long-term outcome of patients with intermittent claudication who underwent revascularization compared with a group initially treated without revascularization. METHODS: Patients with symptoms of intermittent claudication and a diagnosis of peripheral arterial disease were recruited from outpatient clinics at three hospitals in Queensland, Australia. Based on variation in the practices of different vascular specialists, patients were either treated by early revascularization or received initial conservative treatment. Patients were followed in outpatient clinics using linked hospital admission record data. The primary outcome was the requirement for major amputation. Kaplan-Meier curves, Cox regression and competing risks analyses were used to compare major amputation rates. RESULTS: Some 456 patients were recruited; 178 (39·0 per cent) underwent early revascularization and 278 (61·0 per cent) had initial conservative treatment. Patients were followed for a mean(s.d.) of 5·00(3·37) years. The estimated 5-year major amputation rate was 6·2 and 0·7 per cent in patients undergoing early revascularization and initial conservative treatment respectively (P = 0·003). Early revascularization was associated with an increased requirement for major amputation in models adjusted for other risk factors (relative risk 5·40 to 4·22 in different models). CONCLUSION: Patients presenting with intermittent claudication who underwent early revascularization appeared to be at higher risk of amputation than those who had initial conservative treatment.

Short communication: Ovine leukocyte telomere length is associated with variation in the cortisol response to systemic bacterial endotoxin challenge.

Stress has been associated with biological aging and numerous age-related diseases. This may be due, in part, to accelerated shortening of telomeres, which are critical genomic structures that cap and protect chromosomal ends. Dysfunction of the hypothalamic-pituitary-adrenal axis may indirectly contribute to telomere shortening if an animal reacts too strongly or weakly to a stressor, leading to accelerated biological aging. In this study, outbred Rideau-Arcott sheep were stress challenged with Escherichia coli endotoxin and classified as high, middle, or low cortisol responders to investigate a potential relationship between cortisol response and age, and telomere length. In the present study, no association was found between age and telomere length. The study, however, revealed shorter telomeres in high and low cortisol responders compared with the middle cortisol responders, which suggests that health and longevity may be compromised in extreme high- and low-stress-responding sheep.

Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness.

Androgenetic alopecia affects both men and women. In men it produces male pattern hair loss with bitemporal recession and vertex baldness. In women it produces female pattern hair loss (FPHL) with diffuse alopecia over the mid-frontal scalp. FPHL occurs as a result of nonuniform hair follicle miniaturization within follicular units. Diffuse alopecia is produced by a reduction in the number of terminal fibres per follicular unit. Baldness occurs only when all hairs within the follicular units are miniaturized and is a relatively late event in women. The concepts of follicular units and primary and secondary hair follicles within follicular units are well established in comparative mammalian studies, particularly in sheep. However, discovery of these structures in the human scalp hair and investigation of the changes in follicular unit anatomy during the development of androgenetic alopecia have provided a clearer understanding of the early stages of androgenetic alopecia and how the male and female patterns of hair loss are related. FPHL is the most common cause of alopecia in women and approximately one-third of adult caucasian women experience hair loss. The impact of FPHL is predominantly psychological. While men anticipate age-related hair loss, hair loss in women is usually unexpected and unwelcome at any age. Treatment options to arrest hair loss progression and stimulate partial hair regrowth for FPHL include the androgen receptor antagonists spironolactone and cyproterone acetate, the 5α-reductase inhibitor finasteride and the androgen-independent hair growth stimulator minoxidil. These treatments appear to work best when initiated early. Hair transplantation should be considered in advanced FPHL that is resistant to medical treatments. Hair transplantation requires well-preserved hair growth over the occipital donor area. The psychological impact of FPHL may also be reduced by cosmetic products that improve the appearance of the hair. These agents work to minimize hair fibre breakage, improve hair volume or conceal visible bald scalp.

Creutzfeldt-Jakob disease with initial right hemiparesis masquerading as a stroke.

The early stage of sporadic Creutzfeldt-Jakob disease is generally characterised by progressive changes in behaviour and intellectual function. While only a few patients have stroke-like onset, Creutzfeldt-Jakob disease with initial monoparesis has been described. In this report, a patient with an unusual sporadic Creutzfeldt-Jakob disease with typical magnetic resonance imaging findings, positive cerebrospinal fluid 14-3-3 brain protein, sharp-wave complexes in electroencephalogram, and initial right hemiparesis is reported.

Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss.

BACKGROUND: Female pattern hair loss (FPHL) is a common trait in which androgens and oestrogens may have a pathogenic role. The aromatase enzyme converts androgens to oestrogens in scalp hair follicles and is differentially expressed in balding and nonbalding scalps of women. Sequence variation in the gene encoding aromatase, CYP19A1, might influence the risk of developing FPHL. OBJECTIVES: To examine the role of CYP19A1 genetic variation in the heritability of FPHL. METHODS: We investigated associations between FPHL and 61 tag single nucleotide polymorphisms (SNPs) representing variation in and around CYP19A1 in 484 caucasian women with grades 3-5 FPHL on the Sinclair scale, and 471 caucasian women with no evidence of hair loss. RESULTS: For the tag SNP rs4646 (overall genotype frequencies: CC, 53.6%; AC, 39.3%; AA, 7.1%), the genotype CC was more frequent in women with FPHL (58.1%) than controls (48.9%) (P = 0.006). Although this result did not achieve experiment-wide significance (P < 0.001 by permutation testing), subanalyses according to sources of recruitment and ages at presentation revealed consistent patterns of association. In particular, young cases (< 40 years) had the highest frequency of the CC genotype (68.2%) among all subgroups. CONCLUSIONS: These findings suggest that the common rs4646 C allele, which has been associated previously with higher circulating oestrogen levels, might be associated with predisposition to FPHL.