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• Multicentre retrospective analysis of 204 patients with suspected papilloedema. • 156 participants fulfilled the Friedman criteria for primary pseudotumor cerebri. • MRI/MRV signs exhibited a sensitivity of 74.8% and specificity of 94.7% for IIH. • CT/CTV signs exhibited a sensitivity of 61.0% and specificity of 100.0% for IIH. The diagnostic utility of neuroradiologic signs associated with idiopathic intracranial hypertension (IIH) for the evaluation of patients presenting with papilloedema remains yet to be elucidated. This multicentre retrospective cohort study assessed consecutive patients presenting with suspected papilloedema to Auckland District Health Board (NZ) and Stanford University Medical Centre (US), between 2005 and 2019, undergoing magnetic resonance imaging and venography (MRI/MRV) or computed tomography and venography (CT/CTV) prior to lumbar puncture assessment for diagnostic suspicion of IIH. Data were collected regarding demographic, clinical, radiologic, and lumbar puncture parameters, and the diagnosis of IIH was determined according to the Friedman criteria for primary pseudotumor cerebri syndrome. A total of 204 participants (174 females; mean ± SD age 29.9 ± 12.2 years) were included, and 156 (76.5%) participants fulfilled the diagnostic criteria for IIH. The presence of any IIH-associated radiologic sign on MRI/MRV demonstrated a sensitivity (95% CI) of 74.8% (65.8%–82.0%) and specificity (95% CI) of 94.7% (82.7%–98.5%), while radiologic signs on CT/CTV exhibited a sensitivity (95% CI) of 61.0% (49.9%–71.2%) and specificity (95% CI) of 100.0% (83.2%–100.0%). In summary, the modest sensitivities of radiologic signs of IIH would support the routine use of lumbar puncture assessment following neuroimaging to secure the diagnosis. However, the high specificities might lend limited support for the judicious deferment of lumbar puncture assessment among typical IIH demographic patients who consent to the inherent small risk of missed pathology, which has been proposed by some clinicians. [ABSTRACT FROM AUTHOR]

• We describe a patient presenting with persistent hiccups, who was found to have primary CNS lymphoma. • Persistent or intractable hiccups may reflect pathology within the brainstem, hypothalamic or supratentorial centres. • Appetite changes can be caused by hypothalamic tumour infiltration. • A first-order Horner's syndrome can arise from brainstem pathology. • A thorough neurological examination forms the cornerstone of localising neuropathology. We present a case of a 42-year-old male presenting with persistent hiccups and a Horner's syndrome, among other symptoms and signs of hypothalamic and brainstem dysfunction. He had a biopsy-proven diffuse infiltrative large primary CNS B-cell lymphoma involving the left fronto-temporal hemisphere, diencephalon and brainstem. The aim of this case report is to highlight key clinical and neuro-anatomical correlations that bring light to the art of the clinical examination. [ABSTRACT FROM AUTHOR]

• We report three cases of lymphoma mimicking sarcoidosis, vasculitis and infection. • Lymphoma can have protean manifestations. Obtaining tissue is key to diagnosis. • Elevated serum ACE is poorly sensitive and insufficiently specific for sarcoidosis. • In the diagnosis of intravascular lymphoma, random skin biopsy can be considered. • Structural and metabolic imaging have complementary roles in lymphoma evaluation. The title "great imitator" refers to conditions which can cause varied manifestations and mimic many diseases. Lymphoma is worthy of this title. We describe three cases of lymphoma in which lymphoma mimicked other diseases causing neurological dysfunction, specifically sarcoidosis, vasculitis and infection respectively. Case 1 was a 66-year-old man with subacute progressive diplopia and gait disturbance and investigations revealing a supratentorial para -falcine soft tissue lesion, mid-thoracic cord enhancement and right axillary mass and an elevated serum ACE. Right axillary mass core biopsy was diagnostic of Burkitt lymphoma. Case 2 was a 50-year-old man with several weeks of constitutional symptoms and development of lower limb weakness and numbness, urinary retention and confusion while in hospital. MRI brain demonstrated multi-territory cerebral infarcts. Intravascular lymphoma was diagnosed on random skin biopsy. Case 3 was a 65-year-old man with several weeks of headache and diplopia on a background of previously treated Burkitt lymphoma. CSF analysis showed a lymphocytic pleocytosis and markedly low glucose with cytologic analysis negative for malignancy. Investigations for an infective cause were negative. FDG-PET demonstrated marked, disseminated spinal and cranial leptomeningeal disease and a multi-focal, intra-dural relapse of Burkitt lymphoma was diagnosed. The varied manifestations in our cases demonstrate the ability for lymphoma to mimic infective, inflammatory, granulomatous (including sarcoidosis) and neoplastic aetiologies. An elevated serum ACE appears insufficiently diagnostic to confirm sarcoidosis and tissue for histological examination should be sought whenever possible. When the diagnosis is uncertain, the possibility of this great imitator should be considered, especially for multi-focal disease. [ABSTRACT FROM AUTHOR]

Background: The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF).Methods and Results: Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Δ; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R2 = 0.13; P < .0001), amino-terminal pro-B-type NP (R2 = 0.22; P < .0001), and estimated glomerular filtration rate (eGFR; R2 = 0.14; P < .0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio [HR] = 1.007 per ng/mL; P < .001), all-cause mortality (HR = 1.008 per ng/mL; P < .001), and HF events (HR = 1.007 per ng/mL; P < .001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R2 = 0.09; P = .002). ΔIGFBP7 was not independently associated with outcome.Conclusions: Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism.Clinical Trial Registration: www.clinicaltrials.gov, NCT00095238. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of resistance training combined with either moderate-intensity endurance or low-volume high-intensity interval training on cardiovascular risk profiles in patients with coronary artery disease.Design: Factorial repeated-measures study design.Methods: Nineteen patients were randomized into moderate-intensity endurance (n = 10) or high-intensity interval (n = 9) groups, and attended 2 supervised exercise sessions a week for 6-months. The first 3-months involved exclusive moderate-intensity endurance or high-intensity interval exercise, after which progressive resistance training was added to both groups for the remaining 3-months. Fitness (VO(2)peak), blood pressure and heart rate, lipid profiles and health related quality of life assessments were performed at pretraining, 3 and 6-months training.Results: VO(2)peak increased from pretraining to 3-months in both groups (moderate-intensity endurance: 19.8 ± 7.3 vs. 23.2 ± 7.4 ml kg(-1)min(-1); high-intensity interval: 21.1 ± 3.3 vs. 26.4 ± 5.2 ml kg(-1)min(-1), p<0.001) with no further increase at 6-months. Self-evaluated health and high-density lipoprotein were increased following 6-months of moderate-intensity endurance exercise, while all remaining indices were unchanged. Low-volume high-intensity interval exercise did not elicit improvements in lipids or health related quality of life. Blood pressures and heart rates were unchanged with training in both groups.Conclusions: Findings from our pilot study suggest improvements in fitness occur within the first few months of training in patients with coronary artery disease, after which the addition of resistance training to moderate-intensity endurance and high-intensity interval exercise elicited no further improvements. Given the importance of resistance training in cardiac rehabilitation, additional research is required to determine its effectiveness when combined with high-intensity interval exercise. [ABSTRACT FROM AUTHOR]

Anterior visual pathway cavernous malformations (CM) are rare diagnoses with poorly-defined natural history and management. A systematic review of all reports of anterior visual pathway CM was performed to identify all English-language articles with histopathologically-proven anterior visual pathway CM published from 1950 to December 2013. Patient demographics, presenting symptoms, CM location, treatment modality and clinical outcome were recorded and analyzed. The case of a 60-year-old woman from our institution with acute-on-chronic visual disturbance secondary to visual pathway CM is presented. Including the current patient, 70 cases of anterior visual pathway CM have been published to our knowledge. The average patient age is 34.8 ± standard deviation of 14.2 years, with a female preponderance (n = 37, 52.9%). The majority of patients had an acute (n = 44; 62.9%; 95% confidence interval [CI] 0.51–0.73) onset of symptoms. In at least 55.6% (n = 40) of patients, the cause of visual disturbance was initially misdiagnosed. The majority (91.4%; n = 64) of patients underwent craniotomy, with complete resection and subtotal resection achieved in 53.1% (n = 34; 95%CI 0.41–0.65) and 17.2% (n = 11; 95%CI 0.10–0.28) of all surgical patients, respectively. Comparing surgically managed patients, complete resection improved visual deficits in 59.0% (n = 20; 95%CI 0.42–0.75), while subtotal resection improved visual deficits in 50.0% (n = 5; 95%CI 0.24–0.76; p = 0.62). CM is an important differential diagnosis for suprasellar lesions presenting with visual disturbance. A high index of suspicion is required in its diagnosis. Expeditious operative management is recommended to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

This clinical series examines the presentation of three adult patients who were found to have de novo anaplastic pilocytic astrocytoma. Initial imaging demonstrated an intracranial mass with histological analysis diagnostic of pilocytic astrocytoma with anaplastic features including necrosis, marked nuclear pleomorphism and a very high mitotic rate leading to the diagnosis of anaplastic pilocytic astrocytoma. We discuss the clinical pitfalls, treatment and implications when managing this condition. [ABSTRACT FROM AUTHOR]

Abstract: Background: Liver metastases (LM) in close contact to hepatic veins (HV) are a frequent cause of unresectability. Reconstruction of hepatic veins is technically difficult and outcomes are poor. Intra-operative radiofrequency ablation (IRFA) with vascular exclusion (VE) may be a useful approach. Methods: Out of 358 patients operated for LM, 22 with LM close to a HV treated by IRFA under VE with at least one year of follow-up were included in this retrospective study. Technical success was evaluated at four months by CT scan of the ablated lesion. Complications; local, hepatic and extra-hepatic recurrence rates, and overall survival are reported. Results: The median number of metastases was 4.5 [range: 1–12]. Seventeen patients had bilateral metastases. The median size of ablated lesions was 2 cm [range: 1–5.5]. Seven complications occurred (1 Grade 1, 2 Grade 3b and 4 Grade IVa), with no mortality. No recurrence of ablated lesions was detected at four months or during follow-up. Seventeen patients had new or extra-hepatic lesions. Median overall survival for colorectal patients was 40 months 95%CI[17.5-not reached]. Conclusions: IRFA plus VE for LM in close contact to a HV is a novel approach, appearing to be a safe and effective technique which can extend the applications of liver metastases surgery. [Copyright &y& Elsevier]

Abstract: Choroid plexus papillomas are rare neoplasms that arise from choroid plexus epithelium. The World Health Organization classification describes three histological grades. Grade I is choroid plexus papilloma, grade II is atypical choroid plexus papilloma and grade III is choroid plexus carcinoma. Progression between grades is rare but documented. We present two adult cases, a 53-year-old female and a 70-year-old male, who demonstrated clear interval histological progression from grade I choroid plexus papilloma to higher grades. [Copyright &y& Elsevier]

BACKGROUND: The majority of Non-Hodgkin's lymphoma (NHL) patients are over 65years. Management is challenging, especially for aggressive lymphoma, and appropriate assessment of efficacy and tolerance specific to this population is crucial. OBJECTIVES: To assess the representation of older patients in randomised controlled trials (RCT) in NHL, examining whether trial eligibility criteria prevent participation, and whether appropriate primary endpoints such as toxicity, quality of life, or geriatric assessment scores are used. METHODS: We searched Medline for articles published in English or French between 1 January 2005 and 31 December 2011 reporting on phase II/III RCT evaluating therapeutic strategies for NHL. Articles were categorised as including or excluding (directly or indirectly) older adults, and features of RCT that included or excluded older patients are compared. RESULTS: We identified 87 relevant RCT: 9 (10.3%) focussed exclusively on patients >65years, 22 (25.3%) directly excluded patients >65years, 47 (54.0%) indirectly excluded older adults through selective inclusion criteria (ECOG status, liver or kidney function, and comorbidities), and 9 (10.3%) did not directly or indirectly exclude patients >65years (although two excluded patients >70years). Proportions of older patients included do not reflect incidence. Trials including older adults were published in journals with lower impact factors and few RCT used appropriate endpoints for older adults. CONCLUSIONS: Older adults are poorly represented in NHL RCT both due to direct age-based exclusion and restrictive inclusion criteria. This situation needs rapid correction to better represent older patients and thus improve cancer management in this highly prevalent population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heart failure (HF) is common in long-term care facilities (LTCs). This study compared mortality and hospitalization rates and examined predictors of these outcomes among new LTC residents with and without HF. METHODS AND RESULTS: This prospective cohort study followed 546 newly admitted residents from 42 LTCs for up to 1 year. Health information was collected from participant and caregiver interviews, physicians' records, diagnostic procedures, and hospitalization records. Multivariate logistic regression modeling determined predictors of hospitalization among residents, and Cox proportional hazards regression determined predictors for time to mortality. HF prevalence was 21.4%. The sample was predominantly (>70%) female, and individuals with HF were significantly older with higher prevalence of reduced left ventricular ejection fraction. Overall annual mortality and hospitalization rates were 24% and 27%, respectively. Among residents with HF, 42% died and 31% were hospitalized within 1 year. Among residents with HF, use of major tranquilizers was the strongest predictor of sooner mortality; use of anticoagulants and major tranquilizers also increased mortality risk, whereas higher baseline function was associated with longer time to mortality. History of peripheral vascular disease was the strongest predictor of hospitalizations among residents with HF, and use of antiplatelet agents and history of any smoking exposure increased this risk. CONCLUSIONS: Among LTC residents, HF is associated with high mortality and hospitalization rates. Many factors contribute to mortality and hospitalizations among residents with HF, and comprehensive HF management programs are needed to improve outcomes. [ABSTRACT FROM AUTHOR]

Abstract: A new genus of nematode, Haycocknema perplexum, causing polymyositis in humans, was first described in two Australian patients from Tasmania in 1998. Three patients with myositis due to the same nematode were reported from northern Queensland in 2008. We report the sixth case from Australia, a 50-year-old man, also from Tasmania. He had a 2-year history of progressive weakness, weight loss of 10kg and dysphagia. Muscle biopsy was initially interpreted as polymyositis with eosinophils. Maximum creatine kinase (CK) level was 5700U/L and full blood examination was normal. He deteriorated after several months of treatment with prednisolone and methotrexate and review of the muscle biopsy showed intramyofibre parasites of H. perplexum. After 3months of treatment with albendazole therapy, he made a very good clinical recovery and his CK decreased to 470U/L. This uniquely Australian parasite can mimic polymyositis and leads to significant irreversible morbidity (two of the previous patients still have weakness and elevated CK after years) and even mortality (one died), if diagnosed late or after corticosteroids. Diagnosis can only be made by histopathology of muscle biopsy. [Copyright &y& Elsevier]

We evaluated the correlation between soil organic carbon (OC) content and metabolic responses of Eisenia fetida earthworms after exposure to phenanthrene (58 ± 3 mg/kg) spiked into seven artificial soils with OC contents ranging from 1 to 27% OC. Principal component analysis of 1H nuclear magnetic resonance (NMR) spectra of aqueous extracts identified statistically significant differences in the metabolic profiles of control and phenanthrene-exposed E. fetida in the 1% OC soil only. Partial least squares analysis identified a metabolic response in the four soils with OC values ≤11% which was well correlated to estimated phenanthrene porewater concentrations. The results suggest that the higher sorption capability of high OC soils decreased the bioavailability of phenanthrene and the subsequent metabolic response of E. fetida. [Copyright &y& Elsevier]

Abstract: We report an illustrative case of a 74-year-old man who, in the absence of intercurrent illness, presented with rapid cognitive decline. MRI showed bilateral, symmetrical, high T2-weighted signal in the anterior basal ganglia and medial thalami, extending to the periaqueductal grey matter, basal ganglia and basal frontal lobes. A 18F-fluorodeoxyglucose–positron emission tomography scan showed widespread reduction of metabolism in the cortex of the frontal, temporal and parietal lobes, posterior cingulate gyrus, precuneus and caudate nuclei, with sparing of the sensorimotor cortex, thalami and lentiform nuclei. A mild vitamin B12 deficiency was found and despite normal thiamine levels, intravenous (IV) thiamine and vitamin B therapy was commenced, with a short course of IV methylprednisolone and tetracycline. Repeat neuropsychological assessment four weeks following treatment revealed increased alertness and interactiveness but significant cognitive decline persisted. Unexpectedly, the patient suffered a transmural anterior myocardial infarction six weeks after presentation and died within 24hours. An a autopsy showed: global reduction in cytochrome oxidase (COX) activity in all skeletal muscles examined; bilateral, symmetrical, hypervascular, focally necrotizing lesions in the substantia nigra, periaqueductal grey matter, superior colliculi, medial thalami anteriorly and posteriorly, as well as in the putamena but the mammillary bodies were not affected. Biochemical analysis of fresh muscle confirmed selective deficiency of complex IV of the oxidative phosphorylation chain. A diagnosis of late-adult onset Leigh syndrome was made. Multiple genetic studies failed to identify the specific underlying mutation. The relevant literature is reviewed. [Copyright &y& Elsevier]

Nuclear magnetic resonance (NMR) – based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. [Copyright &y& Elsevier]

Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-β-cyclodextrin (HPCD) extraction of soil and 1H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC50 value was 750 mg/kg (632–891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of 1H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q 2 = 0.59) than HPCD-extractable phenanthrene concentrations (Q 2 = 0.46) suggesting that 1H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. [Copyright &y& Elsevier]

1H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50–1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65–97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. [Copyright &y& Elsevier]

Abstract: Background: N-terminal B type natriuretic peptide (NT-proBNP) is usually elevated in heart failure (HF) patients with reduced ejection fraction (EF). Less is known about NT-proBNP in HF with preserved EF (HF-PEF). We measured baseline NT-proBNP in 3562 HF-PEF enrolled patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial. Methods and Results: Patients with EF ≥45%, age ≥60 years, and either New York Heart Association (NYHA) II-IV symptoms with HF hospitalization (HFH) within 6 months or NYHA III-IV symptoms with corroborative evidence of HF or structural changes associated with HF-PEF. NT-proBNP (pg/mL) measured centrally using the Elecsys proBNP assay (Roche). Mean age 72 ± 7 years, 60% were women, the investigator indicated HF etiology was hypertension in 64%; the majority were in NYHA III. Medications included diuretics in 82%, angiotensin-converting enzyme inhibitor in 26%, β-blocker in 59%, and spironolactone in 15%. Median NT-proBNP was 341 pg/mL (interquartile range 135 to 974 pg/mL) and geometric mean was 354 pg/mL. In multivariate analysis, the baseline characteristics most strongly associated with higher NT-proBNP levels were atrial fibrillation (ratio of geometric mean 2.59, P < .001), NYHA IV symptoms (1.52, P < .001), lower estimated glomerular filtration rate (1.44, P < .001), and HFH hospitalization within 6 months (1.37, P < .001). Conclusions: Most HF-PEF patients have elevated NT-proBNP levels. The NT-proBNP concentrations were related to baseline characteristics generally associated with worse outcomes for HF patients. [Copyright &y& Elsevier]

Abstract: Three women (aged 21–36 years) developed acute illnesses that were similar to epidemic encephalitis lethargica. Each presented with a neuropsychiatric disturbance that was succeeded by pyrexia, a fluctuating conscious state and involuntary movements including oculogyria. Cerebrospinal fluid examination showed a predominantly lymphocytic pleocytosis (64–120×106 cells/L) and oligoclonal bands were detected in two cases. Two patients died, while the third made a gradual recovery. Post-mortem examination in the two fatal cases showed changes of lymphocytic meningitis and focal diencephalic lymphocytic infiltration, although these changes were mild relative to the effects of the clinical illness. The diagnosis of sporadic encephalitis lethargica relies on identifying shared clinical features with the past epidemic disease plus circumstantial evidence of immunological activity from laboratory investigations and some tests of exclusion of other disorders. [Copyright &y& Elsevier]

Abstract: Background: Matrix metalloproteinases (MMPs) can alter myocardial extracellular matrix and thereby contribute to adverse ventricular remodeling in progressive heart failure (HF). We hypothesized that increased plasma MMP levels correlate with increased left ventricular (LV) volumes and reduced LV ejection fraction (LVEF) in patients with HF. Methods and Results: In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, patients with symptomatic HF and LVEF <0.40 were randomized to receive various combinations of therapies with candesartan, enalapril, and metoprolol CR. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and LVEF were determined by radionuclide angiography at baseline and at Week 43. Baseline and Week 43 plasma MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in 184 patients in this substudy. At baseline, plasma MMP-9 correlated positively with ESV (Spearman''s rank correlation coefficient ρ = 0.17, P = .02) and negatively with LVEF (ρ = –0.18, P = .01). After 43 weeks, LVEF, EDV, and ESV increased significantly (all P < .01); MMP-2 level increased (P = .01), but MMP-9 and TIMP-1 levels did not change significantly overall in the study population. Temporal changes in MMP-9 level were inversely correlated with changes in LVEF (ρ = –0.16, P = .04). In multivariable analysis adjusting for clinical characteristics and treatment, a smaller proportional change in MMP-9 level after 43 weeks (below versus above median) predicted a concurrent improvement in LVEF (odds ratio = 2.35, 95% CI 1.24–4.46; P < .01). Similar relationships for MMP-2 and TIMP-1 were not observed. Conclusions: Elevated plasma MMP-9 levels correlated with lower LVEF and higher ESV, whereas increasing MMP-9 levels are associated with a concurrent deterioration of LV function. These findings suggest that monitoring of plasma markers of myocardial matrix remodeling may provide important prognostic information with respect to ongoing adverse LV remodeling in HF patients. [Copyright &y& Elsevier]

Abstract: Background: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age ≥60 years, heart failure symptoms, an ejection fraction ≥45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan. [Copyright &y& Elsevier]

Abstract: We present an overview of a portable underway water quality monitoring system (RUM-Rapid Underway Monitoring), developed by integrating several off-the-shelf water quality instruments to provide rapid, comprehensive, and spatially referenced ‘snapshots’ of water quality conditions. We demonstrate the utility of the system from studies in the Northern Great Barrier Reef (Daintree River) and the Moreton Bay region. The Brisbane dataset highlights RUM’s utility in characterising plumes as well as its ability to identify the smaller scale structure of large areas. RUM is shown to be particularly useful when measuring indicators with large small-scale variability such as turbidity and chlorophyll-a. Additionally, the Daintree dataset shows the ability to integrate other technologies, resulting in a more comprehensive analysis, whilst sampling offshore highlights some of the analytical issues required for sampling low concentration data. RUM is a low cost, highly flexible solution that can be modified for use in any water type, on most vessels and is only limited by the available monitoring technologies. [Copyright &y& Elsevier]

Abstract: Keratocytes are specialised cells that produce and maintain corneal stromal matrix and play a key role in corneal wound healing. Abnormal functioning of these cells is likely to play a central role in corneal disorders, such as keratoconus, which in many cases leads to corneal blindness if untreated. The genetic basis of keratoconus is poorly understood but it is likely that apoptosis pathways are involved. The current paper proposes a novel hypothesis for the treatment and prevention of corneal blindness in disorders such as keratoconus as an alternative to the gold standard treatment of penetrating or partial thickness keratoplasty. The proposed hypothesis involves the isolation, purification and transplantation of keratocyte progenitor cells (KPC), with introduction into stroma via femtosecond laser channels in diseased corneal stroma using a carrier medium. The success of this approach will depend upon the viability, migration, and cell division of introduced KPC and production of normal stromal matrix. Results from previous studies suggest that cellular transplantation is possible and may lead to healthy stromal matrix production and remission of a disease phenotype in patients affected with disorders such as keratoconus. If the current hypothesis proves to be correct, it may offer an alternative to invasive keratoplasty for treatment of corneal disorders such as keratoconus that cause significant morbidity for millions of people worldwide. [Copyright &y& Elsevier]

Abstract: We present a 40-year-old man with conus medullaris syndrome secondary to a cystic lesion of the ventriculus terminalis (CLVT) and review the relevant literature. The patient presented with 4 years of worsening right leg weakness, and examination showed bilateral fasciculations and hyporeflexia. MRI showed a cystic lesion at T11–12. He was managed with a T11–12 laminectomy and fenestration of an intramedullary cyst. A total of 32 patients, including ours, have been described since 1968: 24 were female with a mean age of 46.6 years. All patients presented symptomatically: five were managed conservatively, four using percutaneous aspiration under MRI guidance, and 22 with open surgery. We conclude that symptomatic patients are best managed surgically, although percutaneous aspiration is an emerging technique. [ABSTRACT FROM AUTHOR]

Abstract: A patient with a known family history of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) due to the MT-TL1 m.3243A>G mutation presented with mild myalgia and very minor upper limb proximal muscle weakness. Muscle histology revealed low levels of cytochrome oxidase-negative fibres and non-specific myositis. Using the last “hot cycle” polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), the MELAS MT-TL1 m.3243A>G mutation was only detected in urine, and not in hair, blood or skeletal muscle. This report highlights the need to screen various tissues to achieve an accurate mitochondrial genetic diagnosis and suggests the likelihood of myositis arising secondary to the MELAS MT-TL1 m.3243A>G mutation. [Copyright &y& Elsevier]

A biofouling resistant passive sampler for ammonia, where the semi-permeable barrier is a microporous hydrophobic gas-diffusion membrane, has been developed for the first time and successfully applied to determine the time-weighted average concentration of ammonia in estuarine and coastal waters for 7 days. Strategies to control biofouling of the membrane were investigated by covering it with either a copper mesh or a silver nanoparticle functionalised cotton mesh, with the former approach showing better performance. The effects of temperature, pH and salinity on the accumulation of ammonia in the newly developed passive sampler were studied and the first two parameters were found to influence it significantly. A universal calibration model for the passive sampler was developed using the Group Method Data Handling algorithm based on seawater samples spiked with known concentrations of total ammonia under conditions ranging from 10 to 30 °C, pH 7.8 to 8.2 and salinity 20 to 35. The newly developed passive sampler is affordable, user-friendly, reusable, sensitive, and can be used to detect concentrations lower than the recently proposed guideline value of 160 μg total NH 3 –N L−1, for a 99% species protection level, with the lowest concentration measured at 17 nM molecular NH 3 (i.e., 8 μg total NH 3 –N L−1 at pH 8.0 and 20 °C). It was deployed at four field sites in the coastal waters of Nerm (Port Phillip Bay), Victoria, Australia. Good agreement was found between molecular ammonia concentrations obtained with passive and discrete grab sampling methods (relative difference, - 12% to - 19%). Image 1 • A 7-day NH 3 gas-diffusion passive sampler (GD-PS) is developed for marine waters. • An antifouling strategy is successfully applied to a GD-PS for the first time. • Effect of temperature, pH and salinity on the PS accumulation is studied. • Temperature and pH affect the ammonia accumulation in the receiving solution. • A single calibration model was created by the Group Method Data Handling algorithm. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure.Background: Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied.Methods: We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak VO(2)) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo(2) or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO(2) <12 mL/kg per minute.Results: NT-proBNP was the most powerful predictor of peak VO(2) (partial R(2) = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak VO(2) (partial R(2) = 0.02, P < .0001). For both peak VO(2) and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak VO(2) <12 mL/kg per minute (c-index, 0.69).Conclusions: In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO(2) and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO(2) who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables. [ABSTRACT FROM AUTHOR]

Background: To assess the safety of symptom-limited exercise testing in patients with New York Heart Association class II-IV heart failure symptoms due to left ventricular systolic dysfunction, we investigated the frequency of all-cause fatal and nonfatal major cardiovascular (CV) events among subjects enrolled in a prospective clinical trial (HF-ACTION). We hypothesized that exercise testing would be safe, as defined by a rate for all-cause death of <0.1 per 1,000 tests and a rate of nonfatal CV events <1.0 per 1,000 tests. Methods: Before enrollment and at 3, 12, and 24 months after randomization, subjects were scheduled to complete a symptom-limited graded exercise test with open-circuit spirometry for analysis of expired gases. To ensure the accurate reporting of exercise test–related events, we report deaths and nonfatal major CV events per 1,000 tests at months 3, 12, or 24 after randomization. Results: A total of 2,331 subjects were randomized into HF-ACTION. After randomization, 2,037 subjects completed 4,411 exercise tests. There were no test-related deaths, exacerbation of heart failure or angina requiring hospitalization, myocardial infarctions, strokes, or transient ischemic attacks. There was one episode each of ventricular fibrillation and sustained ventricular tachycardia. There were no exercise test–related implantable cardioverter defibrillator discharges requiring hospitalization. These findings correspond to zero deaths per 1,000 exercise tests and 0.45 nonfatal major CV events per 1,000 exercise tests (95% CI 0.11-1.81). Conclusions: In New York Heart Association class II-IV patients with severe left ventricular systolic dysfunction, we observed that symptom-limited exercise testing is safe based on no deaths and a rate of nonfatal major CV events that is <0.5 per 1,000 tests. [Copyright &y& Elsevier]

Background: The mechanisms by which exercise training benefits patients with coronary artery disease (CAD) are unclear but may include improved myocardial circulation. The aim of this study was to investigate the effect of exercise training on myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients with stable CAD. Methods: Twelve patients with documented CAD and ischemic ST-segment depression during exercise testing were randomized to exercise training (n = 7) or sedentary life style (control; n = 5) and underwent rubidium-82 positron emission tomography pre- and postintervention. Global left ventricle MBF and regional MBF in 17 left ventricular segments were calculated. Segments with <75% uptake (2 SD below normal) on stress uptake images were defined as abnormal. Results: Exercise training increased global CFR by 20.8% ± 27.9% versus control (10.5 ± 24.1%, P = .0001). In normal segments (exercise training: n = 91; control: n = 46), exercise training did not change resting MBF (−14.1% ± 16.3% vs −8.8% ± 15.6%) and hyperemic MBF (−1.93% ± 19.1% vs 2.86% ± 20.5%, P = NS) and increased in CFR compared to control (17.0% ± 25.5% vs 11.3% ± 23.5%, P = .01). In abnormal segments, the change in resting MBF was not significantly different (−12.6% ± 18.5% exercise [28 segments] vs −2.9% ± 18.0% control [39 segments], P = NS). A significant increase was seen in hyperemic MBF with exercise (12.5% ± 22.1% vs 2.6% ± 16.3%, P = .02) and CFR (32.8% ± 32.3% vs 9.5% ± 24.8%, P = .001). Conclusions: Exercise training increased CFR in normal and diseased segments, and increased hyperemic flow in diseased segments. These data provide preliminary evidence in support of a favorable effect of exercise training on blood flow to ischemic myocardium. [Copyright &y& Elsevier]