Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort.

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures.

Does Immediate Breast Reconstruction Lead to a Delay in Adjuvant Chemotherapy for Breast Cancer? A Meta-Analysis and Systematic Review.

Timely delivery of adjuvant chemotherapy is crucial. With an increasing frequency of immediate breast reconstructions (IBR) following mastectomy (MAS), concerns have arisen regarding its complication rates and effects on time to chemotherapy. The aim was to conduct a systematic review and meta-analysis to determine if there is a prolonged time to chemotherapy (TTC) after IBR and MAS. Electronic databases, reference lists and relevant articles were searched systematically. Eligibility criteria included women receiving adjuvant chemotherapy who underwent either MAS only or MAS and IBR. Random-effects models were used in the analysis. A total of 29 studies were included in qualitative analysis, comprising of 156,000 patients (IBR: 57,159; MAS: 98,841). But 23 studies had sufficient data to be included in the meta-analysis. Sixteen papers concluded there was no difference in TTC compared to MAS. There was a difference of 3.50 days between TTC in IBR versus MAS (95% CI [0.42, 6.57], P value = .0256; IBR = 43.56 days, MAS = 40.38 days). The rate of patients being delayed past 90 days was not significantly higher in IBR (OR = 1.34, 95% CI [0.76, 2.38], P = .310). IBR patients were more likely to have complications compared to the MAS group (OR = 2.04, 95% CI [1.04-4.01], P < .01). We concluded that there is a statistically significant longer time to chemotherapy following IBR of 3.50 days, yet there is no difference in delays past 90 days. Therefore, the longer TTC in IBR is unlikely to be of any clinical significance.

Ocular surface squamous neoplasia in a patient following oral steroids for contralateral necrotising scleritis.

A male patient in his 70s presented with left eye necrotising scleritis. His ocular history was significant for pterygium excision with mitomycin C 3 months prior in the affected eye, open-angle glaucoma, nuclear sclerosis cataract and previous sixth cranial nerve palsy. Scleral culture was negative and blood work was positive for rheumatoid factor and HLA-B27. The patient was treated for necrotising scleritis with oral doxycycline, vitamin C, ranitidine and prednisone with gradual taper over 45 days. Two months after initiating treatment, his necrotising scleritis achieved complete resolution; however, a new-onset ocular surface squamous neoplasia (OSSN) was identified at the temporal limbus of the contralateral eye. He was treated with topical interferon alpha-2b 1 million IU qid and achieved complete resolution after 4 months. The case highlights both the acute precipitation of OSSN following oral steroids and a sight-threatening complication following pterygium excision.

Author Correction: Selective, high-contrast detection of syngeneic glioblastoma in vivo.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Selective, high-contrast detection of syngeneic glioblastoma in vivo.

Glioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour's ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo-/- mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host's glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO-/-) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma.

Use of a modified Liverpool care pathway in a tertiary Asian hospital: is there still a role for it?

BACKGROUND: In 2007, the Care of the Dying clinical coordinated Pathway (CDP) was adapted from the United Kingdom Liverpool Care Pathway (LCP) and implemented in a tertiary hospital in Singapore to improve care in oncology and subsequently renal patients. With concerns about its use after the Neuberger review, an audit of patients on the CDP was performed to determine if the use of such a pathway should be continued locally. METHODS: A two-year retrospective audit of CDP use was conducted. Aspects of communication, initiation of CDP, patient monitoring, medications, nutrition, and hydration were assessed. RESULTS: In the 111 patient records reviewed, there were documented extent of care discussions with 94% of caregivers and 29% of patients before CDP initiation. Of the 88% of CDPs initiated within office hours, 90% fulfilled the inclusion criteria. All patients were monitored at least every eight hours. Seventy-three patients (66%) were prescribed opioids or sedatives and subsequently monitored appropriately, albeit 56% had no documented prior discussion with caregivers regarding medication use. Indications for opioid use were documented for all patients and only one patient had documentation of excessive sedation. Oral feeding and parenteral hydration were continued in 85% and 74% of patients, respectively. CONCLUSION: There was no documented compromise in medication safety, clinical monitoring, and provision of nutrition and hydration for patients on the CDP. However, documentation of important end-of-life decisions and conversations remain poor. Development of an alternative care tool encouraging systematic discussion and documentation of individualized end-of-life care plans should be considered.

Changes in medical students' attitudes towards end-of-life decisions across different years of medical training.

BACKGROUND: Decisions to forgo life-sustaining medical treatments in terminally ill patients are challenging, but ones that all doctors must face. Few studies have evaluated the impact of medical training on medical students' attitudes towards end-of-life decisions and none have compared them with an age-matched group of non-medical students. OBJECTIVE: To assess the effect of medical education on medical students' attitudes towards end-of-life decisions in acutely ill patients. DESIGN: Cross-sectional study. PARTICIPANTS: Four hundred and two students at The Chinese University of Hong Kong. MEASUREMENTS: Completion of a questionnaire focused on end-of-life decisions. MAIN RESULTS: The number of students who felt that cardiopulmonary resuscitation must always be provided was higher in non-medical students (76/90 (84%)) and medical students with less training (67/84 (80%) in year 1 vs. 18/67 (27%) in year 5) (p < 0.001). Discontinuing life-support therapy was more accepted among senior medical students compared to junior medical and non-medical students (27/66 (41%) in year 5 vs. 18/83 (22%) in year 1 and 20/90 (22%) in non-medical students) (p = 0.003). An unexpectedly large proportion of non-medical students (57/89 (64%)) and year 1 medical students (42/84 (50%)) found it acceptable to administer fatal doses of drugs to patients with limited prognosis. Euthanasia was less accepted with more years of training (p < 0.001). When making decisions regarding limitation of life-support therapy, students chose to involve patients (98%), doctors (92%) and families (73%) but few chose to involve nurses (38%). CONCLUSIONS: Medical students' attitudes towards end-of-life decisions changed during medical training and differed significantly from those of non-medical students.