Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review.

Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson's disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.

Diagnostic challenges for dementia in Australia: are blood-based biomarkers the solution?

The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in technology, however, now allow reliable measurement of blood biomarkers that could improve diagnosis in a range of settings. We discuss the most promising biomarker candidates for translation into clinical practice and research in the near future.

Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms.

AIMS: Myocardial infarction (MI) accelerates atherosclerosis and greatly increases the risk of recurrent cardiovascular events for many years, in particular, strokes and MIs. Because B cell-derived autoantibodies produced in response to MI also persist for years, we investigated the role of B cells in adaptive immune responses to MI. METHODS AND RESULTS: We used an apolipoprotein-E-deficient (ApoE-/-) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells. One week after inducing MI in atherosclerotic mice, we depleted B cells using an anti-CD20 antibody. This treatment prevented subsequent immunoglobulin G accumulation in plaques and MI-induced accelerated atherosclerosis. In gain of function experiments, we purified spleen B cells from mice 1 week after inducing MI and transferred these cells into atherosclerotic ApoE-/- mice, which greatly increased immunoglobulin G (IgG) accumulation in plaque and accelerated atherosclerosis. These B cells expressed many cytokines that promote humoural immunity and in addition, they formed germinal centres within the spleen where they differentiated into antibody-producing plasma cells. Specifically deleting Blimp-1 in B cells, the transcriptional regulator that drives their terminal differentiation into antibody-producing plasma cells prevented MI-accelerated atherosclerosis. Alarmins released from infarcted hearts were responsible for activating B cells via toll-like receptors and deleting MyD88, the canonical adaptor protein for inflammatory signalling downstream of toll-like receptors, prevented B-cell activation and MI-accelerated atherosclerosis. CONCLUSION: Our data implicate early B-cell activation and autoantibodies as a central cause for accelerated atherosclerosis post-MI and identifies novel therapeutic strategies towards preventing recurrent cardiovascular events such as MI and stroke.

Presenting symptoms of COVID-19 and clinical outcomes in hospitalised older adults.

BACKGROUND: In July 2020, a COVID-19 outbreak was recognised in the geriatric wards at a subacute campus of the Royal Melbourne Hospital affecting patients and staff. Patients were also admitted to this site after diagnosis in residential care. AIMS: To describe the early symptoms and the outcomes of COVID-19 in older adults. METHODS: Patients diagnosed with COVID-19 at the facility in July or August 2020 were identified and their medical records were examined to identify symptoms present before and after their diagnosis and to determine their outcomes. RESULTS: Overall, 106 patients were identified as having COVID-19, with median age of 84.3 years (range 41-104 years); 64 were diagnosed as hospital inpatients after a median length of stay of 49 days, 31 were transferred from residential aged care facilities with a known diagnosis and 11 were diagnosed after discharge. There were 95 patients included in an analysis of symptom type and timing onset. Overall, 61 (64.2%) were asymptomatic at the time of diagnosis of COVID-19, having been diagnosed through screening initiated on site. Of these, 88.6% developed symptoms of COVID-19 within 14 days. The most common initial symptom type was respiratory, but there was wide variation in presentation, including fever, gastrointestinal and neurological symptoms, many initially not recognised as being due to COVID-19. Of 104 patients, 32 died within 30 days of diagnosis. CONCLUSIONS: COVID-19 diagnosis is challenging due to the variance in symptoms. In the context of an outbreak, asymptomatic screening can identify affected patients early in the disease course.

Subfascial endoscopic perforator surgery (SEPS) for treating venous leg ulcers.

BACKGROUND: Venous leg ulcers are complex, costly, and their prevalence is expected to increase as populations age. Venous congestion is a possible cause of venous leg ulcers, which subfascial endoscopic perforator surgery (SEPS) attempts to address by removing the connection between deep and superficial veins (perforator veins). The effectiveness of SEPS in the treatment of venous leg ulcers, however, is unclear. OBJECTIVES: To assess the benefits and harms of subfascial endoscopic perforator surgery (SEPS) for the treatment of venous leg ulcers. SEARCH METHODS: In March 2018 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions that examined the use of SEPS independently or in combination with another intervention for the treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, assessed risk of bias, and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included four RCTs with a total of 322 participants. There were three different comparators: SEPS plus compression therapy versus compression therapy (two trials); SEPS versus the Linton procedure (a type of open surgery) (one trial); and SEPS plus saphenous surgery versus saphenous surgery (one trial). The age range of participants was 30 to 82, with an equal spread of male and female participants. All trials were conducted in hospital settings with varying durations of follow-up, from 18 months to 6 years. One trial included participants who had both healed and active ulcers, with the rest including only participants with active ulcers.There was the potential for reporting bias in all trials and performance bias and detection bias in three trials. Participants in the fourth trial received one of two surgical procedures, and this study was at low risk of performance bias and detection bias.SEPS + compression therapy versus compression therapy (2 studies; 208 participants)There may be an increase in the proportion of healed ulcers at 24 months in people treated with SEPS and compression therapy compared with compression therapy alone (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.03 to 1.33; 1 study; 196 participants); low-certainty evidence (downgraded twice, once for risk of bias and once for imprecision).It is uncertain whether SEPS reduces the risk of ulcer recurrence at 24 months (RR 0.85, 95% CI 0.26 to 2.76; 2 studies; 208 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The included trials did not measure or report the following outcomes; time to complete healing, health-related quality of life (HRQOL), adverse events, pain, duration of hospitalisation, and district nursing care requirements.SEPS versus Linton approach (1 study; 39 participants)It is uncertain whether there is a difference in ulcer healing at 24 months between participants treated with SEPS and those treated with the Linton procedure (RR 0.95, 95% CI 0.83 to 1.09; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).It is also uncertain whether there is a difference in risk of recurrence at 60 months: (RR 0.47, 95% CI 0.10 to 2.30; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The Linton procedure is possibly associated with more adverse events than SEPS (RR 0.04, 95% CI 0.00 to 0.60; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The outcomes time to complete healing, HRQOL, pain, duration of hospitalisation and district nursing care requirements were either not measured, reported or data were not available for analysis.SEPS + saphenous surgery versus saphenous surgery (1 study; 75 participants)It is uncertain whether there is a difference in ulcer healing at 12 months between participants treated with SEPS and saphenous surgery versus those treated with saphenous surgery alone (RR 0.96, 95% CI 0.64 to 1.43; 1 study; 22 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).It is also uncertain whether there is a difference in the risk of recurrence at 12 months: (RR 1.03, 95% CI 0.15 to 6.91; 1 study; 75 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).Finally, we are uncertain whether there is an increase in adverse events in the SEPS group (RR 2.05, 95% CI 0.86 to 4.90; 1 study; 75 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).The outcomes time to complete healing, HRQOL, serious adverse events, pain, duration of hospitalisation, and district nursing care requirements were either not measured, reported or data were not available for analysis. AUTHORS' CONCLUSIONS: The role of SEPS for the treatment of venous leg ulcers remains uncertain. Only low or very low-certainty evidence was available for inclusion. Due to small sample sizes and risk of bias in the included studies, we were unable to determine the potential benefits and harms of SEPS for this purpose. Only four studies met our inclusion criteria, three were very small, and one was poorly reported. Further high-quality studies addressing the use of SEPS in venous leg ulcer management are likely to change the conclusions of this review.

Diagnostic yield of pleural fluid cytology in malignant effusions: an Australian tertiary centre experience.

BACKGROUND: Timely diagnosis of malignant pleural effusions is critical to guide prognosis and management decisions. Cytological analysis of pleural fluid has been the first-line diagnostic test for many decades, with highly variable reported sensitivities of 40-90%. Its diagnostic accuracy in modern practice in Australia needs to be understood. AIMS: To determine the diagnostic yield of pleural fluid cytology for the detection of malignant pleural effusions and to determine the aetiologies of pleural effusions at our centre. METHODS: The study involved the retrospective chart review of all pleural fluid samples submitted for cytological analysis at a tertiary referral centre in Melbourne, Australia, over a 12-month period. Aetiology of all effusions was determined, and sensitivity, specificity, negative predictive value and diagnostic accuracy for the detection of malignant pleural effusions were calculated. We also examined diagnostic yield based on tumour cell type. RESULTS: Of the 153 cases analysed, 61 (39.9%) were malignant. Lung cancers accounted for 44.3% of malignant effusions, followed by mesothelioma (18%), ovarian carcinoma (11.5%) and lymphoma (8.2%). The commonest single causes of a benign effusion were cardiac (16.3%) and parapneumonic (13%). Sensitivity for diagnosis of malignant effusions was 67.2% overall, but 87.9% for adenocarcinomas and only 45.5% for mesothelioma. CONCLUSION: Tumour type is an important determinant of pleural fluid cytology diagnostic yield. Cytology has good sensitivity and specificity for the diagnosis of adenocarcinoma, but if another tumour type is suspected, particularly mesothelioma, clinicians should be aware of the limitations.

Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD. METHODS: MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305). RESULTS: The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified. DISCUSSION: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Prevalence of cerebral microbleeds in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia: A systematic review and meta-analysis.

Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31-36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-ß burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-ß burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted.

Geriatric home-based rehabilitation in Australia: Preliminary data from an inpatient bed-substitution model.

BACKGROUND: The REStORing health of acutely unwell adulTs (RESORT) is an observational longitudinal cohort, including geriatric rehabilitation inpatients aged ≥65 years admitted to a geriatrician-led rehabilitation service at a tertiary hospital. The aim of this study is to describe a home-based bed-substitution rehabilitation model for geriatric inpatients, including patient phenotype, and health outcomes at preadmission, admission, discharge, and three-month follow-up. METHODS: A standardized Comprehensive Geriatric Assessment was performed on admission and discharge, including demographics (home situation, cognitive impairment, medical diagnoses, etc.), frailty (Clinical Frailty Scale (CFS)), mobility (patient-reported and Functional Ambulation Classification), physical performance (Short Physical Performance Battery (SPPB), handgrip strength), and functional independence (Activities of Daily Living (ADL), Instrumental ADL (IADL)). Service provision data (health care staff visits, length of stay (LOS), and negative events (e.g., falls)) were extracted from medical records. Three-month outcomes included mobility, ADL and IADL scores, institutionalization, and mortality. RESULTS: Ninety-two patients were included with a mean age of 81.1 ± 7.8 years, 56.5% female. Twenty-nine (31.5%) patients lived alone, 39 (42.4%) had cognitive impairment and the commonest geriatric rehabilitation admission reason was falls (n = 30, 32.6%). Patients received care from nurses, physicians, and a median of four (interquartile range (IQR) 3-6) allied health disciplines for a median LOS of 13.0 days (IQR 10.0-15.0). On a population level, patient mobility and functional independence worsened from preadmission to admission. CFS, SPPB, ADL, and IADL scores improved from admission to discharge, and seven (7.6%) patients fell. At three-month follow-up, patient-reported mobility was comparable to preadmission baseline, but functional independence (ADL, IADL) scores worsened for 27/69 (39.1%) and 28/63 (44.4%), respectively. CONCLUSIONS: Hospitalization-associated decline in mobility and functional independence improved at discharge and three-months, but was not fully reversed in the multidisciplinary home-based geriatric rehabilitation bed-substitution service. Future research should compare outcomes to equivalent hospital-based geriatric rehabilitation and evaluate patient perspectives.

Geriatric Rehabilitation Inpatients Roam at Home! A Matched Cohort Study of Objectively Measured Physical Activity and Sedentary Behavior in Home-Based and Hospital-Based Settings.

OBJECTIVES: This study aimed to describe objectively measured physical activity and sedentary behavior in geriatric rehabilitation patients receiving care in the home-based compared to the hospital-based setting. DESIGN: Observational matched cohort study. SETTING AND PARTICIPANTS: Home-based (patient's home) or hospital-based (ward) geriatric rehabilitation was delivered to inpatients within the REStORing health of acutely unwell adulTs (RESORT) observational, longitudinal cohort of the Royal Melbourne Hospital (Melbourne, Victoria, Australia). METHODS: Patients were asked to wear ActivPAL4 accelerometers for 1 week and were assessed by a comprehensive geriatric assessment at admission, discharge, and followed up after 3 months. Hospital-based patients were matched to home-based patients for sex and baseline physical function [Short Physical Performance Battery (SPPB), activities (instrumental) of daily living, and Clinical Frailty Scale]. Differences in patient characteristics and physical activity (total, standing and walking durations, number of steps and sit-to stand transitions) and sedentary behavior (total, sitting and lying durations) were assessed. RESULTS: A total of 159 patients were included: 18 home-based [mean age: 81.9 ± 8.6 years, 38.9% female, median (interquartile range [IQR]) SPPB: 7.0 (5.0-9.0)] and 141 hospital-based [mean age: 82.9 ± 7.8 years, 57.4% female, median (IQR) SPPB: 1.0 (0.0-4.0)] patients, of whom 18 were matched [mean age: 80.1 ± 7.4 years, 38.9% female, median (IQR) SPPB: 6.5 (4.8-10.0)]. Median physical activity measures were consistently higher in home-based patients compared to the total group of hospital-based patients. After matching, physical activity measures remained >2.4 times higher and were significantly different for all measures (total physical activity, standing and walking durations, and steps) except for sit-to-stand transitions. Sedentary behaviors were similar with home-based patients spending non-significantly more time sitting but significantly less time lying than hospital-based patients (matched and total). CONCLUSIONS AND IMPLICATIONS: Home-based inpatients are more physically active than hospital-based inpatients independent of matching for sex and baseline physical function, which supports home-based geriatric rehabilitation.

Subacute combined degeneration of the spinal cord masking motor neuron disease: a case report.

BACKGROUND: Subacute combined degeneration of the spinal cord is a potentially reversible myelopathy typically associated with vitamin B12 deficiency. There is predominant involvement of spinal cord posterior and lateral tracts, and manifestations include peripheral paraesthesia, impaired proprioception, gait disturbance, neuropathy and cognitive changes. Motor neuron disease (MND) is an unremittingly progressive neurodegenerative disorder involving upper and lower motor neurons with an average prognosis of 2-3 years. The diagnosis is clinical and may be supported by electromyography. A subset of MND occurs concurrently with frontotemporal dementia (FTD-MND) and may be initially misdiagnosed as a primary psychotic disorder. CASE PRESENTATION: We describe a 57-year-old Caucasian woman who presented with confusion and dysarthria. Low vitamin B12 levels and MRI findings led to an initial diagnosis of subacute combined degeneration of the spinal cord. Despite treatment, persistent dysarthria and presence of both upper and lower motor neuron signs on clinical examination prompted further assessment. Electromyography supported the diagnosis of MND. Comorbid chronic paranoid schizophrenia complicated the diagnostic process. We discuss overlapping features between B12 deficiency and MND as well as the neuropsychiatric overlap of B12 deficiency, FTD-MND and chronic schizophrenia. CONCLUSIONS: Firstly, variability in neurocognitive and imaging manifestations of B12 deficiency can limit delineation of other pathologies. Failure to improve following correction of nutritional deficiencies warrants further investigation for an alternate diagnosis. Secondly, re-evaluation of patients with comorbid mental health conditions is important in reaching timely and accurate diagnoses.

Preoperative Staging by EBUS in cN0/N1 Lung Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging the radiologically normal mediastinum has been reported with inconsistent findings. We assessed the sensitivity of systematic staging using EBUS-TBNA for detection of radiologically occult mediastinal metastases in cN0/N1 lung cancer. METHODS: Studies evaluating EBUS-TBNA for systematic mediastinal staging in cN0/N1 lung cancer were identified by systematic review. Data extracted included: participant age and sex; EBUS-TBNA protocol; stage determined by radiology, EBUS-TBNA and surgery; 2×2 tables. Primary outcome was diagnostic accuracy of EBUS-TBNA for detection of unsuspected N2/N3 disease. RESULTS: We identified 1173 articles. In total, 13 were included in a qualitative review and 9 (1146 patients) in a quantitative meta-analysis. Mean prevalence of N2/N3 disease was 15% (6% to 24%). EBUS-TBNA had pooled sensitivity of 49% [95% confidence interval (CI), 41%-57%], pooled specificity of 100% (95% CI, 99%-100%), mean negative predictive value 91% (82% to 100%) for detection of unsuspected N2/N3 metastases. Number needed to test to detect occult N2/N3 disease was 14 (95% CI, 10.8-16.3), which halved with addition of per-esophageal endoscopic ultrasound. CONCLUSION: Preoperative systematic staging by EBUS-TBNA of early lung cancer can reduce postoperative upstaging. Sensitivity for detection of radiologically occult mediastinal metastases seems lower than selective sampling of pathologic lymph nodes. Verification of negative results by mediastinoscopy in selected cases remains of value.

Sensitive molecular testing methods can demonstrate NSCLC driver mutations in malignant pleural effusion despite non-malignant cytology.

Malignant pleural effusion (MPE) may be diagnosed by cytologic evaluation of pleural fluid, though false negative results can occur. Pleural effusions may provide a source of tumour material for genotyping in lung cancer patients. Detection of MPE may be improved through use of highly sensitive molecular techniques. We identified five patients with non-small cell lung cancer (NSCLC) with initial pleural fluid samples that were non-malignant on cytology, but were subsequently clinically confirmed to have MPE. Tumour mutation status was confirmed via routine testing of diagnostic clinical specimens. Cytologically negative pleural fluid cell-block specimens were analysed by amplicon-based parallel sequencing (APS) for somatic mutations commonly detected in NSCLC, and selected cases by improved and complete enrichment CO-amplification at lower denaturation temperature PCR (ICECOLD PCR) for known mutations. Mutations were detected in three out of three (sensitivity 100%) cytologically non-malignant pleural fluids from patients with a known mutation: two patients with known Kirsten rat sarcoma (KRAS) mutation demonstrated the same KRAS mutation in their pleural fluids by APS, both at approximately 2% mutant allele frequency. In one patient with a known KRAS mutation, ICECOLD PCR detected the same KRAS variant at 0.7% frequency. No mutations were detected in patients with wild-type findings from reference samples (specificity 100%). Sensitive DNA sequencing methods can detect cancer-driver mutations in cytologically non-malignant pleural fluid specimens from NSCLC patients with MPE. Our findings demonstrate the feasibility of sensitive molecular diagnostic techniques for improvement of diagnostic assessment of pleural effusions in patients with lung cancer.

Aspirin in venous leg ulcer study (ASPiVLU): study protocol for a randomised controlled trial.

BACKGROUND: Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing. METHODS/DESIGN: This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks. DISCUSSION: The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.