Predictors of recurrence following local excision for early-stage anal squamous cell carcinoma.

INTRODUCTION: There is increasing use of local excision (LE) for definitive treatment of early-stage anal squamous cell carcinoma (ASCC) to avoid the morbidity associated with chemoradiotherapy (CRT). However, the importance of different histological variables on risk of recurrence is poorly understood. METHODS: A detailed analysis of patient characteristics, histology results, recurrence patterns and salvage treatment was conducted in consecutive T1/T2N0 ASCC patients treated by LE 2010-2021 across a UK regional cancer network multi-disciplinary team (MDT). Associations between potential predictors of disease recurrence were explored using chi-squared and Kruskal-Wallis tests for categorical and continuous variables respectively. RESULTS: Of 621 ASCC patients discussed in the network MDT, 164 had early-stage disease (T1/T2 N0). Of these, 36 (22%) were deemed suitable for LE (median age 61 years, female to male ratio 2:1). Twenty-two LE tumours were T1; 14 were T2. There were 12 well-differentiated tumours, 21 moderate and 3 poorly-differentiated. Seven out of 36 LE patients (19.4%) developed recurrence, all of whom went on to have salvage treatment with CRT (n = 4), re-excision (n = 2) or radiotherapy (n = 1). Predictors of disease recurrence following LE were: tumour differentiation (p = 0.024), tumour depth (p = 0.033) and R1 resection margin (p = 0.034). Tumour stage and site (margin/canal) were non-significant. CONCLUSION: LE for T1/T2 N0 ASCC of the margin or canal is a viable treatment strategy to avoid the morbidity associated with CRT and salvage treatments are still available for patients that develop recurrence. Tumour differentiation, depth and margin status are all important factors to consider when discussing management of early-stage ASCC.

Ageing of juvenile coral grouper (Plectropomus maculatus) reveals year-round spawning and recruitment: implications for seasonal closures.

Temporal patterns in spawning and juvenile recruitment can have major effects on population size and the demographic structure of coral reef fishes. For harvested species, these patterns are crucial in determining stock size and optimizing management strategies such as seasonal closures. For the commercially important coral grouper (Plectropomus spp.) on the Great Barrier Reef, histological studies indicate peak spawning around the summer new moons. Here we examine the timing of spawning activity for P. maculatus in the southern Great Barrier Reef by deriving age in days for 761 juvenile fish collected between 2007 and 2022, and back-calculating settlement and spawning dates. Age-length relationships were used to estimate spawning and settlement times for a further 1002 juveniles collected over this period. Unexpectedly, our findings indicate year-round spawning activity generates distinct recruitment cohorts that span several weeks to months. Peak spawning varied between years with no clear association with environmental cues, and little to no alignment with existing seasonal fisheries closures around the new moon. Given the variability and uncertainty in peak spawning times, this fishery may benefit from additional and longer seasonal closures, or alternative fisheries management strategies, to maximize the recruitment contribution from periods of greatest reproductive success.

EZ Clear for simple, rapid, and robust mouse whole organ clearing.

Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevent the widespread adoption of these methods. Here, we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hr in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, samples processed with EZ Clear can be subjected to downstream applications, such as tissue embedding and cryosectioning followed by standard histology or immunofluorescent staining without loss of fluorescence signal from endogenous or synthetic reporters. Furthermore, we demonstrate that wholemount adult mouse brains processed with EZ Clear can be successfully immunolabeled for fluorescent imaging while still retaining signal from endogenous fluorescent reporters. Overall, the simplicity, speed, and flexibility of EZ Clear make it easy to adapt and implement in diverse imaging modalities in biomedical research.

A human model of arteriovenous malformation (AVM)-on-a-chip reproduces key disease hallmarks and enables drug testing in perfused human vessel networks.

Brain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene. Our goal was to develop an in vitro model that would allow for simultaneous morphological and functional phenotypic data capture in real time during AVM disease progression. By generating human endothelial cells harboring a clinically relevant mutation found in most human patients (activating mutations within the small GTPase KRAS) and seeding them in a dynamic microfluidic cell culture system that enables vessel formation and perfusion, we demonstrate that vessels formed by KRAS4AG12V mutant endothelial cells (ECs) were significantly wider and more leaky than vascular beds formed by wild-type ECs, recapitulating key structural and functional hallmarks of human AVM pathogenesis. Immunofluorescence staining revealed a breakdown of adherens junctions in mutant KRAS vessels, leading to increased vascular permeability, a hallmark of hemorrhagic stroke. Finally, pharmacological blockade of MEK kinase activity, but not PI3K inhibition, improved endothelial barrier function (decreased permeability) without affecting vessel diameter. Collectively, our studies describe the creation of human KRAS-dependent AVM-like vessels in vitro in a self-assembling microvessel platform that is amenable to phenotypic observation and drug delivery.

Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.

Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.

Identification of diverse tumor endothelial cell populations in malignant glioma.

BACKGROUND: Glioblastoma is the most common and aggressive type of primary brain tumor, as most patients succumb to the disease less than two years after diagnosis. Critically, studies demonstrate that glioma recruits surrounding blood vessels, while some work suggests that tumor stem cells themselves directly differentiate into endothelial cells, yet the molecular and cellular dynamics of the endothelium in glioma are poorly characterized. The goal of this study was to establish molecular and morphological benchmarks for tumor associated vessels (TAVs) and tumor derived endothelial cells (TDECs) during glioblastoma progression. METHODS: Using In-Utero Electroporation and CRISPR/Cas9 genome engineering to generate a native, immunocompetent mouse model of glioma, we characterized vascular-tumor dynamics in three dimensions during tumor progression. We employed bulk and single-cell RNA-Sequencing to elucidate the relationship between TAVs and TDECs. We confirmed our findings in a patient derived orthotopic xenograft (PDOX) model. RESULTS: Using a mouse model of glioma, we identified progressive alteration of vessel function and morphogenesis over time. We also showed in our mouse model that TDECs are a rare subpopulation that contributes to vessels within the tumor, albeit to a limited degree. Furthermore, transcriptional profiling demonstrates that both TAVs and TDECs are molecularly distinct, and both populations feature extensive molecular heterogeneity. Finally, the distinct molecular signatures of these heterogeneous populations are also present in human glioma. CONCLUSIONS: Our findings show extensive endothelial heterogeneity within the tumor and tumor microenvironment and provide insights into the diverse cellular and molecular mechanisms that drive glioma vascularization and angiogenesis during tumorigenesis.

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Clinical Usefulness of Transcranial Doppler as a Screening Tool for Early Cerebral Hypoxic Episodes in Patients with Moderate and Severe Traumatic Brain Injury.

BACKGROUND: Brain tissue oxygenation (PbtO2) in traumatic brain injury (TBI) is known to be dependent on cerebral blood flow (CBF) which remains difficult to assess during the very early phase of TBI management. This study evaluates if blood flow velocity measurement with 2D color-coded transcranial Doppler (TCD) can predict cerebral hypoxic episodes in moderate-to-severe TBI measured with a PbtO2 probe. METHODS: This is a prospective observational study of serial TCD measurements to assess blood flow velocity and its association with PbtO2. Measurements were done bilaterally on the middle cerebral artery (MCA) early after the insertion of PbtO2 monitoring, daily for 5 days and during dynamic challenge tests. Physiological parameters affecting PbtO2 and Doppler velocities were collected simultaneously (PaO2, PaCO2, hemoglobin [Hb] level, intracranial pressure, and cerebral perfusion pressure [CPP]). RESULTS: We enrolled 17 consecutive patients with a total of 85 TCD studies. Using 2D color-coded TCD, signal acquisition was successful in 96% of the cases. Twenty-nine (34%) TCD measures were performed during an episode of cerebral hypoxia (PbtO2 ≤ 20 mmHg). For early episodes of cerebral hypoxia (occurring ≤ 24 h from trauma), all Vmean < 40 cm/s were associated with an ipsilateral PbtO2 ≤ 20 mmHg (positive predictive value 100%). However, when considering all readings over the course of the study, however, we found no correlation between PbtO2 and MCA's mean blood flow velocity (Vmean). Vmean is also positively correlated with PaCO2, whereas PbtO2 is also correlated with PaO2, CPP, and Hb level. CONCLUSIONS: Early TCD measurements compatible with low CBF (mean velocity < 40 cm/s) detect brain tissue hypoxia early after TBI (≤ 24 h) and could potentially be used as a screening tool before invasive monitoring insertion to help minimize time-sensitive secondary injury. Various factors influence the relationship between Vmean and PbtO2, affecting interpretation of their interaction after 24 h.

Impact of a checklist used by pharmacists on hospital antimicrobial use: a patient-level interrupted time series study.

BACKGROUND: Antimicrobial misuse leading to drug resistance is a growing concern for clinicians. Improving antimicrobial stewardship programmes through development of new tools could be part of the solution. AIM: To evaluate antimicrobial use in hospitalized patients after implementation of an antimicrobial checklist for ward-based clinical pharmacists. METHODS: A checklist based on quality indicators of optimal antimicrobial use was implemented to standardize hospital pharmacists' assessments of antimicrobial therapy. Antimicrobial use metrics from adults hospitalized during the control and intervention periods were assessed in an interrupted time series analysis of individual patient data. The primary endpoint was days of therapy (DOT) for all antimicrobials per 1000 days present for included patients. Secondary endpoints were the DOT of extended-spectrum antimicrobials (DOT-ES), length of therapy of all antimicrobials (LOT) and the number of pharmacist interventions. FINDINGS: One-thousand six-hundred and nineteen patients were included: 800 and 819 in the pre- and post-checklist implementation periods, respectively. As indicated by the point estimates and their 95% confidence intervals (CIs), there were no changes in trend for DOT, DOT-ES or LOT. A change in level was not found for the DOT, while a change of -118 DOT-ES [-209,-28] and -51 LOT [-97,-4] was documented. Furthermore, pharmacists' interventions regarding antimicrobials increased by 18.7% (14.0, 23.5) and progress notes by 32.3% (27.8, 36.8). CONCLUSION: An antimicrobial checklist used by ward-based clinical pharmacists did not decrease DOT for all antimicrobials, but decreased DOT-ES and LOT upon its implementation.

Protein adhesins as vaccine antigens for Group A Streptococcus.

Group A Streptococcus (GAS) is a globally important human pathogen that causes a broad spectrum of disease ranging from mild superficial infections to severe invasive diseases with high morbidity and mortality. Currently, there is no vaccine available for human use. GAS produces a vast array of virulence factors including multiple adhesin molecules. These mediate binding of the bacteria to host tissues and are essential in the initial phases of infection. Prophylactic vaccination with adhesins is a promising vaccine strategy and many GAS adhesins are currently in development as vaccine candidates. The most advanced candidates, having entered clinical trials, are based on the M protein, while components of the pilus and a number of fibronectin-binding proteins are in pre-clinical development. Adhesin-based vaccines aim to induce protective immunity via two main mechanisms: neutralisation where adhesin-specific antibodies block the ability of the adhesin to bind to host tissue and opsonisation in which adhesin-specific antibodies tag the GAS bacteria for phagocytosis. This review summarises our current knowledge of GAS adhesins and their structural features in the context of vaccine development.

Estimating the likely true changes in rheumatic fever incidence using two data sources.

Acute rheumatic fever (ARF) continues to produce a significant burden of disease in New Zealand (NZ) Maori and Pacific peoples. Serious limitations in national surveillance data mean that accurate case totals cannot be generated. Given the changing epidemiology of ARF in NZ and the major national rheumatic fever prevention programme (2012-2017), we updated our previous likely true case number estimates using capture-recapture analyses. Aims were to estimate the likely true incidence of ARF in NZ and comment on the changing ability to detect cases. Data were obtained from national hospitalisation and notification databases. The Chapman Estimate partially adjusted for bias. An estimated 2342 likely true new cases arose from 1997 to 2015, giving a mean annual incidence of 2·9 per 100 000 (95% CI 2·5-3·5). Compared with the pre-intervention (2009-2011) baseline incidence (3·4 per 100 000, 95% CI 2·9-4·0), the likely true 2015 incidence declined 44%. Large gaps in data completeness are slowly closing. During the period 2012-2015, 723 cases were identified; 83·8% of notifications were matched to hospitalisation data, and 87·2% of hospitalisations matched to notifications. Despite this improvement, clinicians need to remain aware of the need to notify atypical patients. A possible unintended consequence of the national ARF prevention programme is increased misdiagnosis.

A Dilatometric Study of Tempering Complemented by Mössbauer Spectroscopy and other Characterization Techniques.

A new approach for non-isothermal tempering analysis utilizing dilatometry is proposed and was carried out on a medium carbon steel with high silicon and additions of Mo and V for secondary hardening. The method includes a second non-isothermal step performed with the same heating rate (2 °C/min) used for the first step in order to create a baseline for analysis. The results were correlated with several other characterization techniques. Mössbauer spectroscopy confirmed the formation of transition carbides by auto-tempering as well as the presence of retained austenite decomposition (stage II) and cementite precipitation (stage III), which demonstrated significant overlap. Electrical resistivity measurements were correlated with dislocation densities obtained through X-ray diffraction analysis. Transmission electron microscopy dark field images confirmed the secondary hardening assessment from dilatometry.

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

Decreased and increased relative acetabular volume predict the development of osteoarthritis of the hip: an osteological review of 1090 hips.

AIMS: Recently, there has been considerable interest in quantifying the associations between bony abnormalities around and in the hip joint and osteoarthritis (OA). Our aim was to investigate the relationships between acetabular undercoverage, acetabular overcoverage, and femoroacetabular impingement (FAI) with OA of the hip, which currently remain controversial. MATERIALS AND METHODS: A total of 545 cadaveric skeletons (1090 hips) from the Hamann-Todd osteological collection were obtained. Femoral head volume (FHV), acetabular volume (AV), the FHV/AV ratio, acetabular version, alpha angle and anterior femoral neck offset (AFNO) were measured. A validated grading system was used to quantify OA of the hip as minimal, moderate, or severe. Multiple linear and multinomial logistic regression were used to determine the factors that correlated independently with the FHV, AV, and the FHV/AV ratio. RESULTS: Female cadavers had smaller FHVs (standardised beta -0.382, p < 0.001), and AVs (standardised beta -0.351, p < 0.001), compared with male patients, although the FHV/AV ratio was unchanged. Every 1° increase in alpha angle increased the probability of having moderate OA of the hip compared with minimal OA by 7.1%. Every 1 mm decrease in AFNO increased the probability of having severe or moderate OA of the hip, compared with minimal OA, by 11% and 9%, respectively. The relative risk ratios of having severe OA of the hip compared with minimal OA were 7.2 and 3.3 times greater for acetabular undercoverage and overcoverage, respectively, relative to normal acetabular cover. CONCLUSION: Acetabular undercoverage and overcoverage were independent predictors of increased OA of the hip. The alpha angle and AFNO had modest effects, supporting the hypothesis that bony abnormalities both in acetabular dysplasia and FAI are associated with severe OA. Cite this article: Bone Joint J 2017;99-B:432-9.

Asymptomatic and symptomatic urethral gonorrhoea in men who have sex with men attending a sexual health service.

OBJECTIVES: Guidelines regarding whether men who have sex with men (MSM) without symptoms of urethritis should be screened for urethral gonorrhoea differ between countries. We examined the rate of asymptomatic urethral gonorrhoea in MSM using sensitive nucleic acid amplification testing. METHODS: This study was conducted on consecutive MSM attending the Melbourne Sexual Health Centre between July 2015 and May 2016 for sexually transmitted infections screening. Gonorrhoea testing with the Aptima Combo 2 (AC2) assay was performed on all urine specimens obtained from MSM, whether symptoms of urethritis were present or not. Men were classified as having: typical discharge if they reported symptoms suggesting purulent discharge; other symptoms if they reported other symptoms of urethritis; and no symptoms if they reported no urethral symptoms. RESULTS: During the study period, there were 7941 clinic visits by 5947 individual MSM with 7090 urine specimens obtained from 5497 individual MSM tested with the AC2 assay. Urethral gonorrhoea was detected in 242 urine specimens from 228 individual MSM. The majority (189/242, 78%, 95% CI 73-83) reported typical discharge, 27/242 (11%, 95% CI 8-16) reported other urethral symptoms, and 26/242 (11%, 95% CI 7-15) reported no symptoms on the day of presentation and testing. Among men with urethral gonorrhoea, the proportions with concurrent pharyngeal or rectal gonorrhoea were 32% (134/210) and 64% (74/235), respectively. The mean interval between last reported sexual contact and onset of typical urethral discharge, where present, was 3.9 days. CONCLUSION: The findings from our study lend support to guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.

Markers of dietary protein intake are associated with successful weight loss in the POUNDS Lost trial.

To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24-h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m-2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (-4.4 kg [95% CI: -5.9, -3.0]) than for women in the lowest carbohydrate group (-1.8 kg [95% CI: -3.2, -0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow-up protein intake was associated with greater weight loss, consistent with the 'protein spread theory'. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months.

Development of LRRK2 Inhibitors for the Treatment of Parkinson's Disease.

Linkage and genome-wide association studies have identified a genetic risk locus for late-onset Parkinson's disease in chromosome 12, originally identified as PARK6. The causative gene was identified to code for a large multifunctional protein, LRRK2 (leucine-rich repeat kinase 2). The combined genetic and biochemical evidence supports a hypothesis in which the LRRK2 kinase function is causally involved in the pathogenesis of sporadic and familial forms of PD, and therefore that LRRK2 kinase inhibitors could be useful for treatment. Although LRRK2 has so far not been crystallised, the use of homology modelling and crystallographic surrogates has allowed the optimisation of chemical structures such that compounds of high selectivity with good brain penetration and appropriate pharmacokinetic properties are now available for understanding the biology of LRRK2 in vitro and in vivo. This chapter reviews LRRK2 biology, the structural biology of LRRK2 and gives an overview of inhibitors of LRRK2.

Role of prophylactic antibiotics in lesser toe fusion surgery: A prospective randomised controlled trial.

BACKGROUND: This prospective randomised controlled trial was performed to determine whether the incidence of local infection is reduced in patients who are administered prophylactic antibiotics for lesser toe fusion surgery. METHODS: 100 adult patients undergoing toe fusion surgery that required K-wires to be left in situ for 4-6 weeks were randomly allocated into those who received prophylactic antibiotics (Group 1, n=48) and those who did not (Group 2, n=52). Patients were followed up regularly and during each visit K-wire insertion sites were assessed for signs of pin tract infection. RESULTS: The mean age of Group 1 was 58.0 (SD 17.5) and Group 2 was 62.7 years (SD 14.7). The overall infection rate was 4%. Three patients (6.2%) in Group 1 and one patient (1.9%) in Group 2 developed signs of infection, which required treatment by oral antibiotics. All infections were low grade. There were no features suggestive of osteomyelitis in any of the patients. CONCLUSION: The overall infection rate in lesser toe fusion surgery is low and that using prophylactic antibiotics does not reduce the incidence. Inappropriate use of antibiotics, however, may contribute to the development of antibiotic resistance and adds to healthcare costs.

Follow-up cancer care: perspectives of Aboriginal and Torres Strait Islander cancer survivors.

PURPOSE: The purpose of this study was to explore Indigenous Australian cancer survivors' perspectives of follow-up cancer care and management.. METHODS: This is a qualitative study employing individual interviews with 21 Indigenous cancer survivors (13 females, 8 males) recruited from a rural primary health service and large tertiary hospital in Brisbane, Queensland. Yarning methods were used to conduct semi-structured interviews. Yarning is a culturally appropriate, informal conversational process emphasising the importance of storytelling. RESULTS: Findings describe a range of ways in which follow-up cancer care is experienced with four major categories elucidated, namely: links to tertiary health services, links to primary health services, communication between tertiary and primary health services, and lost in transition. Both positive and negative experiences were described; however, the importance of timely and informative discharge information, continuity of care, good communication between tertiary and primary health services, and strong therapeutic relationships were salient issues raised by participants. CONCLUSIONS: These findings highlight the importance of establishing strong therapeutic relationships between patients and tertiary and primary health professionals. Also important for survivorship is provision of discharge summaries or care plans at discharge for survivors and general practitioners as well as access to a range of allied health services. Alternative means for follow-up could be investigated for regional and rural survivors to facilitate convenient and cost-effective follow-up care. Finally, provision of responsive and flexible follow-up care to cater for the diverse range of needs and preferences of cancer survivors is required. A patient navigator available across the cancer continuum could go some way to addressing this.