A comparison between different patient groups for diabetes management during phases of the COVID-19 pandemic: a retrospective cohort study in Ontario, Canada.

BACKGROUND: With the onset of the COVID-19 pandemic and the large uptake in virtual care in primary care in Canada, the care of patients with type 2 diabetes has been greatly affected. This includes decreased in-person visits, laboratory testing and in-person assessments such as blood pressure (BP). No studies have investigated if these changes persisted with pandemic progression, and it is unclear if shifts impacted patient groups uniformly. The purpose of this paper was to examine changes in diabetes care pre, early, and later pandemic across different patient groups. METHODS: A repeated cross-sectional design with an open cohort was used to investigate diabetes care in adults with type 2 diabetes for a 6-month interval from March 14 to September 13 over three consecutive years: 2019 (pre-pandemic period), 2020 (early pandemic period), and 2021 (later pandemic period). Data for this study were abstracted from the University of Toronto Practice-Based Research Network (UTOPIAN) Data Safe Haven, a primary care electronic medical records database in Ontario, Canada. Changes in diabetes care, which included primary care total visits, in-person visits, hemoglobin A1c (HbA1c) testing, and BP measurements were evaluated across the phases of the pandemic. Difference in diabetes care across patient groups, including age, sex, income quintile, prior HbA1c levels, and prior BP levels, were assessed. RESULTS: A total of 39,401 adults with type 2 diabetes were included in the study. Compared to the 6-month pre-pandemic period, having any in-person visits decreased significantly early pandemic (OR = 0.079 (0.076-0.082)), with a partial recovery later pandemic (OR = 0.162 (95% CI: 0.157-0.169). Compared to the pre-pandemic period, there was a significant decrease early pandemic for total visits (OR = 0.486 (95% CI: 0.470-0.503)), HbA1c testing (OR = 0.401 (95% CI: 0.389-0.413)), and BP measurement (OR = 0.121 (95% CI: 0.116-0.125)), with partial recovery later pandemic. CONCLUSIONS: All measures of diabetes care were substantially decreased early pandemic, with a partial recovery later pandemic across all patient groups. With the increase in virtual care due to the COVID-19 pandemic, diabetes care has been negatively impacted over 1-year after pandemic onset.

A Sister-Group Comparison of Branching and Pedicellariae in Brittlestars (Echinodermata: Ophiuroidea).

Branching of arms and presence of pedicellariae are characters among ophiuroids found only in the order Euryalida (snakestars and basketstars). Family Asteronychidae has neither character; family Euryalidae has 2 small clades with branched arms; and family Gorgonocephalidae has all species with pedicellariae and 3 or 4 clades with branched arms. Despite the rare occurrence of these characters in the Ophiuroidea, they might be key adaptations within the Euryalida that have led to relatively high diversification. Sister-group comparison of the distribution of these 2 characters among taxa indicates that neither character alone explains diversity patterns within the order. In particular, branching restricted to the tips of arms seems not strongly adaptive, probably for the lack of integration of basal forks with the disc. On the other hand, 2 clades of gorgonocephalids with basal branching exceed their snakestar sister groups in numbers of species, indicating an advantage of branching within the family. Unfortunately, the analysis cannot benefit from statistics, for at least 5 independent comparisons are required for a one-tailed sign test. Because branching and pedicellariae are probably not independent variables, future sister-group comparisons should be done only within the Gorgonocephalidae once clade structure is better clarified with increased taxon sampling (10 currently missing genera) and resolution of intra-generic inconsistencies in the most recent cladograms available. Branching might confer upon gorgonocephalid basketstars a more efficient use of pedicellariae for upstream capture of zooplankton over their snakestar relatives as well as over the Euryalidae, which retain ancestral downstream capture by mucus-laden podia.

GermanDie Verzweigung der Arme und das Vorhandensein von Pedicellarien sind Merkmale unter Ophiuroiden, die nur in der Ordnung Euryalida (Schlangensterne mit unverzweigten Armen und Korbsterne mit verzweigten Armen) vorkommen. Die Familie Asteronychidae hat kein Merkmal; die Familie Euryalidae hat zwei kleine Kladen mit verzweigten Armen; und die Familie Gorgonocephalidae hat alle Arten mit Pedicellarien und drei oder vier Kladen mit verzweigten Armen. Trotz des seltenen Vorkommens dieser Merkmale in den Ophiuroidea könnten sie Schlüsselanpassungen innerhalb der Euryalida sein, die zu einer relativ hohen Diversifizierung geführt haben. Eine Schwestergruppenanalyse der Verteilung dieser beiden Merkmale unter den Taxa zeigt, dass keines der Merkmale allein die Diversitätsmuster innerhalb der Ordnung erklärt. Insbesondere die auf die Armspitzen beschränkte Verzweigung scheint nicht stark adaptiv zu sein, wahrscheinlich wegen fehlender Integration von Basalgabeln in die Scheibe. Andererseits übertreffen zwei Kladen von Gorgonocephaliden mit basaler Verzweigung ihre Schlangenstern-Schwestergruppen in der Anzahl der Arten, was auf einen Vorteil der Verzweigung innerhalb der Familie hinweist. Leider kann die Analyse nicht von Statistiken profitieren, da für einen einseitigen Vorzeichentest mindestens fünf unabhängige Vergleiche erforderlich sind. Da Verzweigung und Pedicellariae wahrscheinlich keine unabhängigen Variablen sind, sollten zukünftige Schwestergruppenvergleiche nur innerhalb der Gorgonocephalidae durchgeführt werden, sobald die Klade-Struktur durch vermehrte Taxon-Stichproben (10 derzeit fehlende Gattungen) und durch Auflösung von Inkonsistenzen innerhalb der Gattungen in den neuesten verfügbaren Kladogrammen besser aufgeklärt ist. Die Verzweigung könnte gorgonocephaliden Korbsternen eine effizientere Nutzung von Pedicellarien für den stromaufwärts gelegenen Fang von Zooplankton gegenüber ihren Schlangenstern-Verwandten sowie gegenüber den Euryalidae verleihen, die den stromabwärts gelegenen Fang durch schleimbeladene Füsschen der Vorfahren beibehalten.

Biochemically recurrent prostate cancer: rationalisation of the approach to imaging.

AIM: To assess the utility of magnetic resonance imaging (MRI) in addition to the additive benefit of the conventional imaging techniques, computed tomography (CT) and nuclear medicine (NM) bone scintigraphy, for investigation of biochemical recurrence (BCR) post-prostatectomy where access to prostate specific membrane antigen (PSMA) positron-emission tomography (PET)-CT is challenging. MATERIALS AND METHODS: Relevant imaging over a 5-year period was reviewed. Ethical approval was granted by the internal review board. All patients with suspected BCR, defined as a PSA ≥0.2 ng/ml on two separate occasions, underwent a retrospective imaging review. This was performed on PACS archive search database in a single centre using search terms "PSA" and "prostatectomy" in the three imaging methods; MRI, CT, and NM bone scintigraphy. All PSMA PET CT performed were recorded. RESULTS: One hundred and eighty-five patients were identified. Patients with an MRI pelvis that demonstrated distant metastases (i.e., pelvic bone metastases or lymph node involvement more cranial to the bifurcation of the common iliac arteries) were more likely to have a positive CT and/or NM bone scintigraphy. The Pearson correlation coefficient between the findings of M1 disease at MRI pelvis and the presence of distant metastases at CT thorax, abdomen, pelvis and NM bone scintigraphy was calculated at 0.81 (p<0.01) and 0.91 (p<0.01) respectively. CONCLUSION: An imaging strategy based on risk stratification and technique-specific selection criteria leads to more appropriate use of resources, and in turn, increases the yield of conventional imaging methods. MRI prostate findings can be used to predict the additive value of CT/NM bone scintigraphy allowing a more streamlined approach to their use.

Optimal reconstructive strategies in the setting of post-mastectomy radiotherapy - A systematic review and network meta-analysis.

BACKGROUND: A third of breast cancer patients require mastectomy. In some high-risk cases postmastectomy radiotherapy (PMRT) is indicated, threatening reconstructive complications. Several PMRT and reconstruction combinations are used. Autologous flap (AF) reconstruction may be immediate (AF→PMRT), delayed-immediate with tissue expander (TE [TE→PMRT→AF]) or delayed (PMRT→AF). Implant-based breast reconstruction (IBBR) includes immediate TE followed by PMRT and conversion to permanent implant (PI [TE→PMRT→PI]), delayed TE insertion (PMRT→TE→PI), and prosthetic implant conversion prior to PMRT (TE→PI→PMRT). AIM: Perform a network metanalysis (NMA) assessing optimal sequencing of PMRT and reconstructive type. METHODS: A systematic review and NMA was performed according to PRISMA-NMA guidelines. NMA was conducted using R packages netmeta and Shiny. RESULTS: 16 studies from 4182 identified, involving 2322 reconstructions over three decades, met predefined inclusion criteria. Studies demonstrated moderate heterogeneity. Multiple comparisons combining direct and indirect evidence established AF-PMRT as the optimal approach to avoid reconstructive failure, compared with IBBR strategies (versus PMRT→TE→PI; OR [odds ratio] 0.10, CrI [95% credible interval] 0.02 to 0.55; versus TE→PMRT→PI; OR 0.13, CrI 0.02 to 0.75; versus TE→PI→PMRT OR 0.24, CrI 0.05 to 1.05). PMRT→AF best avoided infection, demonstrating significant improvement versus PMRT→TE→PI alone (OR 0.12, CrI 0.02 to 0.88). Subgroup analysis of IBBR found TE→PI→PMRT reduced failure rates (OR 0.35, CrI 0.15-0.81) compared to other IBBR strategies but increased capsular contracture. CONCLUSION: Immediate AF reconstruction is associated with reduced failure in the setting of PMRT. However, optimal reconstructive strategy depends on patient, surgeon and institutional factors. If IBBR is chosen, complication rates decrease if performed prior to PMRT. PROSPERO REGISTRATION: CRD 42020157077.

Use of esophageal stents to relieve dysphagia during neoadjuvant therapy prior to esophageal resection: a systematic review.

Esophageal cancer stenting offers symptomatic relief for patients suffering from dysphagia. There are limited data to support their use to relieve dysphagia and improve nutrition during neoadjuvant therapy with some concern that they may negatively impact oncological outcomes. The aim of this systematic review was to quantify the impact of esophageal stents on outcomes prior to resection with curative intent. A literature search was performed using Embase, Medline, PubMed, PubMed Central, the Cochrane library for articles pertaining to esophageal stent use prior to or during neoadjuvant chemotherapy or chemoradiotherapy in patients planned for curative esophagectomy. Data extracted included basic demographics, clinical, nutritional and oncologic outcomes. A total of 9 studies involving 465 patients were included. Esophageal stent use resulted in a significant improvement in mean dysphagia scores in the immediate post stent period but failed to demonstrate any positive changes in weight, body mass index (BMI) or albumin. Only 33% of stented patients ultimately progressed to potential curative surgical resection and stents were associated with reduced R0 resection rates and lower overall survival. This systematic review shows that, although esophageal stenting is associated with improvements in dysphagia during neoadjuvant therapy, their effect on improving patient nutritional status is less clear and they may be associated with poorer long-term oncological outcomes. Stents should be used with caution in patients who are being considered for potentially curative resection of esophageal malignancies and other strategies of nutritional supplementation should be considered.

Identifying patients' support needs following critical illness: a scoping review of the qualitative literature.

BACKGROUND: Intensive care survivors suffer chronic and potentially life-changing physical, psychosocial and cognitive sequelae, and supporting recovery is an international priority. As survivors' transition from the intensive care unit to home, their support needs develop and change. METHODS: In this scoping review, we categorised patients' support needs using House's Social Support Needs framework (informational, emotional, instrumental, appraisal) and mapped these against the Timing it Right framework reflecting the patient's transition from intensive care (event/diagnosis) to ward (stabilisation/preparation) and discharge home (implementation/adaptation). We searched electronic databases from 2000 to 2017 for qualitative research studies reporting adult critical care survivors' experiences of care. Two reviewers independently screened, extracted and coded data. Data were analysed using a thematic framework approach. RESULTS: From 3035 references, we included 32 studies involving 702 patients. Studies were conducted in UK and Europe (n = 17, 53%), Canada and the USA (n = 6, 19%), Australasia (n = 6, 19%), Hong Kong (n = 1, 3%), Jordan (n = 1, 3%) and multi-country (n = 1, 3%). Across the recovery trajectory, informational, emotional, instrumental, appraisal and spiritual support needs were evident, and the nature and intensity of need differed when mapped against the Timing it Right framework. Informational needs changed from needing basic facts about admission, to detail about progress and treatments and coping with long-term sequelae. The nature of emotional needs changed from needing to cope with confusion, anxiety and comfort, to a need for security and family presence, coping with flashbacks, and needing counselling and community support. Early instrumental needs ranged from managing sleep, fatigue, pain and needing nursing care and transitioned to needing physical and cognitive ability support, strength training and personal hygiene; and at home, regaining independence, strength and return to work. Appraisal needs related to obtaining feedback on progress, and after discharge, needing reassurance from others who had been through the ICU experience. CONCLUSIONS: This review is the first to identify the change in social support needs among intensive care survivors as they transition from intensive care to the home environment. An understanding of needs at different transition periods would help inform health service provision and support for survivors.

Monitoring of trace metal accumulation in two South African farmed mussel species, Mytilus galloprovincialis and Choromytilus meridionalis.

Mussels pose health risks to consumers through accumulation of trace metals from the ocean. Saldanha Bay, South Africa, has heavy industry and international shipping, creating concerns over pollution levels for aquaculture facilities. Samples of C. meridionalis and M. galloprovincialis were collected from mussel rafts over two-years and analysed for trace metal content using Inductively Coupled Plasma Mass Spectrometry. Aluminium, Cr, Fe, Zn, Cd and Pb were higher in M. galloprovincialis, while C. meridionalis accumulated more Cu and Mn. Temporal fluctuations occurred for Fe and As concentrations in C. meridionalis, and Fe, As, Hg and Pb in M. galloprovincialis. Arsenic exceeded South African regulatory limits (3 mg/kg) once in each species (max = 3.4 mg/kg w.w.). Lead concentrations in M. galloprovincialis were within EU regulatory limits for bivalves (1.5 mg/kg) but exceeded SA regulatory limits for fish (0.5 mg/kg) four times. Overall, farmed mussels from Saldanha Bay were determined to be safe for human consumption.

Stoma rods in abdominal surgery: a systematic review and metaanalyses.

BACKGROUND: Stoma rods are used traditionally to prevent retraction of loop stomas into the abdominal cavity. However, there is very little evidence to support or refute their use. The aim of the present systematic review and metaanalysis was to assess the current data on stoma rods in loop stomas. The primary outcomes were stoma necrosis and stoma retraction. METHODS: A systematic review and metaanalyses were conducted using the preferred reporting items for systematic reviews and metaanalysis guidelines (PRISMA). The study protocol was registered prospectively on PROSPERO. An electronic search was performed by two reviewers independently using predefined search strategy and Medline. Bibliographies of selected studies were screened for additional references. RevMan was used to generate forest plots and calculate odds ratios and 95% confidence intervals (CIs). RESULTS: In total, five studies were identified that met inclusion criteria, including four randomized controlled trials. Three studies examined only ileostomies, while one included both colostomies and ileostomies, and one only examined colostomies. In total, 561 patients underwent a stoma with a rod compared to 443 without. There was a higher rate of dermatitis (rod 29.86% vs no rod 16% OR 2.65; 95% CI 1.79-3.93) and stoma necrosis (rod 7% vs no rod 1.15% OR 5.58; 95% CI 1.85-16.84) in the rod group, but there was no significant difference in stoma retraction (rod 2.28% vs no rod 3.45%; OR 0.7; 95% CI 0.32-1.54). CONCLUSIONS: Stoma rods do not reduce the incidence of stoma retraction and instead lead to increased rates of dermatitis and stoma necrosis.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Comparing accelerometer, pedometer and a questionnaire for measuring physical activity in bronchiectasis: a validity and feasibility study?

BACKGROUND: There are challenges for researchers and clinicians to select the most appropriate physical activity tool, and a balance between precision and feasibility is needed. Currently it is unclear which physical activity tool should be used to assess physical activity in Bronchiectasis. The aim of this research is to compare assessment methods (pedometer and IPAQ) to our criterion method (ActiGraph) for the measurement of physical activity dimensions in Bronchiectasis (BE), and to assess their feasibility and acceptability. METHODS: Patients in this analysis were enrolled in a cross-sectional study. The ActiGraph and pedometer were worn for seven consecutive days and the IPAQ was completed for the same period. Statistical analyses were performed using SPSS 20 (IBM). Descriptive statistics were used; the percentage agreement between ActiGraph and the other measures were calculated using limits of agreement. Feedback about the feasibility of the activity monitors and the IPAQ was obtained. RESULTS: There were 55 (22 male) data sets available. For step count there was no significant difference between the ActiGraph and Pedometer, however, total physical activity time (mins) as recorded by the ActiGraph was significantly higher than the pedometer (mean ± SD, 232 (75) vs. 63 (32)). Levels of agreement between the two devices was very good for step count (97% agreement); and variation in the levels of agreement were within accepted limits of ±2 standard deviations from the mean value. IPAQ reported more bouted- moderate - vigorous physical activity (MVPA) [mean, SD; 167(170) vs 6(9) mins/day], and significantly less sedentary time than ActiGraph [mean, SD; 362(115) vs 634(76) vmins/day]. There were low levels of agreement between the two tools (57% sedentary behaviour; 0% MVPA10+), with IPAQ under-reporting sedentary behaviour and over-reporting MVPA10+ compared to ActiGraph. The monitors were found to be feasible and acceptable by participants and researchers; while the IPAQ was accepta ble to use, most patients required assistance to complete it. CONCLUSIONS: Accurate measurement of physical activity is feasible in BE and will be valuable for future trials of therapeutic interventions. ActiGraph or pedometer could be used to measure simple daily step counts, but ActiGraph was superior as it measured intensity of physical activity and was a more precise measure of time spent walking. The IPAQ does not appear to represent an accurate measure of physical activity in this population. TRIAL REGISTRATION: Clinical Trials Registration Number NCT01569009 : Physical Activity in Bronchiectasis.

Detection of evoked acetylcholine release in mouse brain slices.

The study of transmitter interactions in reward and motor pathways in the brain, including the striatum, requires methodology to detect stimulus-driven neurotransmitter release events. Such methods exist for dopamine, and have contributed to the understanding of local and behavioral factors that regulate dopamine release. However, factors that regulate release of another key transmitter in these pathways, acetylcholine (ACh), are unresolved, in part because of limited temporal and spatial resolution of current detection methods. We have optimized a voltammetric method for detection of local stimulus-evoked ACh release using enzyme-coated carbon-fiber microelectrodes and fast-scan cyclic voltammetry. These electrodes are based on the detection of H2O2 generated by the actions of acetylcholine esterase and choline oxidase, and reliably respond to ACh in a concentration-dependent manner. Methods for enzyme coating were optimized for mechanical stability that allowed for their use in ex vivo brain slices. We report here the first quantitative assessment of extracellular ACh concentration after local electrical stimulation in dorsal striatum in slices from control mice. The selective detection of ACh under these conditions was confirmed by showing that the response detected in the control slices was absent in slices from mice bred to lack ACh synthesis in the forebrain. These electrodes represent a new tool to study ACh and ACh-dopamine interactions with micrometer spatial resolution.

Precision Measurement of the Radiative ß Decay of the Free Neutron.

The standard model predicts that, in addition to a proton, an electron, and an antineutrino, a continuous spectrum of photons is emitted in the ß decay of the free neutron. We report on the RDK II experiment which measured the photon spectrum using two different detector arrays. An annular array of bismuth germanium oxide scintillators detected photons from 14 to 782 keV. The spectral shape was consistent with theory, and we determined a branching ratio of 0.00335±0.00005[stat]±0.00015[syst]. A second detector array of large area avalanche photodiodes directly detected photons from 0.4 to 14 keV. For this array, the spectral shape was consistent with theory, and the branching ratio was determined to be 0.00582±0.00023[stat]±0.00062[syst]. We report the first precision test of the shape of the photon energy spectrum from neutron radiative decay and a substantially improved determination of the branching ratio over a broad range of photon energies.

Do first impressions count? Frailty judged by initial clinical impression predicts medium-term mortality in vascular surgical patients.

Recognising frailty during pre-operative assessment is important. Frail patients experience higher mortality rates and are less likely to return to baseline functional status following the physiological insult of surgery. We evaluated the association between an initial clinical impression of frailty and all-cause mortality in 392 patients attending our vascular pre-operative assessment clinic. Prevalence of frailty assessed by the initial clinical impression was 30.6% (95% CI 26.0-35.2%). There were 133 deaths in 392 patients over a median follow-up period of 4 years. Using Cox regression, adjusted for age, sex, revised cardiac risk index and surgery (yes/no), the hazard ratio for mortality for frail vs. not-frail was 2.14 (95% CI 1.51-3.05). The time to 20% mortality was 16 months in the frail group and 33 months in the not-frail group. The initial clinical impression is a useful screening tool to identify frail patients in pre-operative assessment.

The use of circular external fixators in the management of lower limb trauma in Dublin: a single surgeon's 20-year experience.

INTRODUCTION: It has been estimated that approximately 520,000 injury presentations are made to Irish accident and emergency departments each year. Fractures account for 20 % of these injuries. Circular external fixators (frames) have been shown to be a safe and effective method of treatment for long bone fractures where internal fixation is impossible or in-advisable. We present the outcomes of all frames applied at our institution for stabilisation of acute fractures over a 20-year period. METHODS AND METHODS: We retrospectively reviewed a prospectively compiled database of all frames applied in our institution and identified all frames which were applied for acute lower limb trauma. RESULTS: We identified 68 fractures in 63 patients. There were 11 femoral fractures and 57 tibial fractures. All fractures were classified using the AO Classification system, and most fractures were Type C fractures. We used an Ilizarov frame for 53 fractures and a Taylor Spatial Frame for 15 fractures. The mean time in frame was 365 days for a femoral fracture and 230 days for a tibial fracture. There were five tibial non-unions giving an overall union rate of 93 %. Factors associated with non-union included high-energy trauma and cigarette smoking. CONCLUSION: The vast majority of lower limb fractures can be treated using 'conventional' methods. Complex fractures which are not amenable to open reduction and internal fixation or cast immobilisation can be treated in a frame with excellent results. The paucity of published reports regarding the use of frames for complex trauma reflects the under-utilisation of the technique.

First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis.

BACKGROUND: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. PATIENTS AND METHODS: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out. RESULTS: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74). CONCLUSIONS: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.

Active surveillance for low-risk prostate cancer: diversity of practice across Europe.

BACKGROUND: Active surveillance (AS) is a recognised treatment option for low-risk prostate cancer (PCa). AIMS: To review AS criteria in terms of patient selection, follow-up and indications for intervention. METHODS: A total of 2,959 potential participants were identified and invited via email to complete an online survey. Only urologists practising in an EU country were eligible to participate. Statistical analyses were carried out using SPSS version 18.0. The χ (2) test was used to compare responses between those who do and do not follow an AS protocol. RESULTS: Response rate was 8% (n = 226). Ninety-seven per cent urologists offer AS; 25% (n = 53/215) within a clinical trial and a further 28% (n = 60/215) using an official AS protocol. Gleason score ≤ 3 + 3 = 6 (87 %, n = 173/200) and prostate-specific antigen (PSA) ≤ 10 ng/ml (86%, n = 170/198) are the commonest selection criteria. There was a statistically significant association between having an AS protocol and using PSA as an eligibility criterion (p = 0.03). For urologists not following a protocol, 11% do not consider PSA as an eligibility criterion and 81% consider PSA ≤ 10 ng/ml to decide on AS, compared to 2 and 90%, respectively, who adhere to a protocol. Twenty-four per cent of urologists without a protocol do not re-biopsy in comparison to 11% with a protocol (p = 0.026). Gleason score progression trigger the most intervention (n = 168/192, 87%). CONCLUSIONS: Urologists not adhering to an AS protocol or participating in a clinical trial appear to apply less rigorous criteria for both eligibility and monitoring in AS.

Opportunities for NanoTheranosis in Lung Cancer and Pulmonary Metastasis.

Malignancies of the lungs, both primary and metastatic, are the leading cause of death worldwide. Over 1.5 million new cases of primary lung cancer are diagnosed annually worldwide with a dismal five-year survival rate of approximately 15%, which remains unchanged despite major efforts and medical advances. As expected, survival for patients with lung metastases is even worse at about 5%. Early detection and staging are fundamental in improving survival rates and selecting the most effective treatment strategies. Recently, nanoparticles have been developed for imaging and treating various cancers, including pulmonary malignancies. In this work, three different examples of nanoparticle configurations for cancer theranosis are presented, namely conventional spherical polymeric nanoparticles with a diameter of ~ 150 nm; and discoidal mesoporous silicon nanoconstructs and discoidal polymeric nanoconstructs with a diameter of ~ 1,000 nm and a height of 400 and 500 nm, respectively. The spherical nanoparticles accumulate in tumors by means of the well-known enhanced permeation and retention effect, whereas sub-micrometer discoidal nanoconstructs are rationally designed to adhere firmly to the tortuous tumor vasculature. All three nanoparticles are characterized for their in vivo performance in terms of magnetic resonance, positron-emission tomography (PET), and optical imaging. Preliminary data on the in vivo and ex vivo PET/CT imaging of breast cancer metastasis in the lungs using discoidal nanoconstructs is presented. In conclusion, opportunities for nanoparticle-based theranosis in primary lung cancer and pulmonary metastasis are presented and discussed.

Modulation of the interstitial fluid pressure by high intensity focused ultrasound as a way to alter local fluid and solute movement: insights from a mathematical model.

High intensity focused ultrasound (HIFU) operated in thermal mode has been reported to reduce interstitial fluid pressure and improve the penetration of large macromolecules and nanoparticles in tumor and normal tissue. Little is understood about how the interstitial fluid pressure and velocity as well as the interstitial macromolecule transport are affected by HIFU exposure. A mathematical model is presented here which sheds light on the initial biophysical changes brought about HIFU. Our continuum model treats tissue as an effective poro-elastic material that reacts to elevated temperatures with a rapid drop in interstitial elastic modulus. Using parameters from the literature, the model is extrapolated to derive information on the effect in tumors, and to predict its impact on the convective and diffusive transport of macromolecular drugs. The model is first solved using an analytical approximation with step-wise changes at each boundary, and then solved numerically starting from a Gaussian beam approximation of the ultrasound treatment. Our results indicate that HIFU causes a rapid drop in interstitial fluid pressure that may be exploited to facilitate convection of macromolecules from vasculature to the exposed region. However, following a short recovery period in which the interstitial fluid pressure is normalized, transport returns to normal and the advantages disappear over time. The results indicate that this effect is strongest for the delivery of large molecules and nanoparticles that are in the circulation at the time of treatment. The model may be easily applied to more complex situations involving effects on vascular permeability and diffusion.