Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%

The Mitochondrial Targets of Neuroprotective Drug Vinpocetine on Primary Neuron Cultures, Brain Capillary Endothelial Cells, Synaptosomes, and Brain Mitochondria

Vinpocetine is considered as neuroprotectant drug and used for treatment of brain ischemia and cognitive deficiencies for decades. A number of enzymes, channels and receptors can bind vinpocetine, however the mechanisms of many effects' are still not clear. The present study investigated the effects of vinpocetine from the mitochondrial bioenergetic aspects. In primary brain capillary endothelial cells the purinergic receptor-stimulated mitochondrial Ca2+ uptake and efflux were studied. Vinpocetine exerted a partial inhibition on the mitochondrial calcium efflux. In rodent brain synaptosomes vinpocetine (30 μM) inhibited respiration in uncoupler stimulated synaptosomes and decreased H2O2 release from the nerve terminals in resting and in complex I inhibited conditions, respectively. In isolated rat brain mitochondria using either complex I or complex II substrates leak respiration was stimulated, but ADP-induced respiration was inhibited by vinpocetine. The stimulation of oxidation was associated with a small extent of membrane depolarization. Mitochondrial H2O2 production was inhibited by vinpocetine under all conditions investigated. The most pronounced effects were detected with the complex II substrate succinate. Vinpocetine also mitigated both Ca2+-induced mitochondrial Ca2+-release and Ca2+-induced mitochondrial swelling. It lowered the rate of mitochondrial ATP synthesis, while increasing ATPase activity. These results indicate more than a single mitochondrial target of this vinca alkaloid. The relevance of the affected mitochondrial mechanisms in the anti ischemic effect of vinpocetine is discussed

Fundus Autofluorescence in Age-related Macular Degeneration

: Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy)

The advantages of intermediate-tier, inter-optometric referral of low risk pigmented lesions

Purpose: Pigmented ocular lesions are commonly encountered by eye-care professionals, and range from benign to sight or life-threatening. After identifying a lesion, the primary care professional must establish the likely diagnosis and decide either to reassure, to monitor or to refer. The increasing use of ocular imaging technologies has contributed to an increase in the detection rate of pigmented lesions and a higher number of referrals, which may challenge existing pathways of health-care delivery. Specialist services may be over-burdened by referring all patients with pigmented lesions for an opinion, while inter-optometric referrals are underutilised. The aim of this study was to describe the referral patterns of pigmented lesions to an optometry led intermediate-tier collaborative care clinic. Methods: We performed a retrospective review of patient records using the list of patients examined at Centre for Eye Health (CFEH) for an initial or follow up pigmented lesion assessment between the 1/7/2013 and the 30/6/2016. Analysis was performed on: patient demographic characteristics, the referrer's tentative diagnosis, CFEH diagnosis and recommended management plan. Results: Across 182 patient records, the primary lesion prompting referral was usually located in the posterior segment: choroidal naevus (105/182, 58%), congenital hypertrophy of the retinal pigment epithelium (CHRPE; 11/182, 6%), chorioretinal scarring (10/182, 5%) or not specified (52/182, 29%). Referrals described a specific request for ocular imaging in 25 instances (14%). The number of cases with a non-specific diagnosis was reduced after intermediate-tier care assessment (from 29% to 10%), while the number of diagnoses with less common conditions rose (from 2% to 21%). There was a 2% false positive referral rate to intermediate-tier care and a first visit discharge rate of 35%. A minority required on-referral to an ophthalmologist (22/182, 12%), either for unrelated incidental ocular findings, or suspicious choroidal naevi. Conditions most amenable to optometric follow up included: 1) chorioretinal scarring, 2) choroidal naevus, and 3) CHRPE. Conclusions: Intermediate-tier optometric eye-care in pigmented lesions (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with less common diagnoses. The majority of cases seen under this intermediate-tier model required only ongoing optometric surveillance

Age-related macular degeneration: Linking clinical presentation to pathology

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze previously uncharacterized and earlier changes in the retina. The challenge for optometrists is to combine all this information into an applicable knowledge base for use in everyday clinical assessment of AMD so that timely and accurate referrals can be made to retinal specialists. This review attempts to address this issue by linking the clinical presentation of AMD with the underlying disease biology. We emphasize the contribution of recent noninvasive imaging technologies to the clinical assessment of early and more advanced AMD including optical coherence tomography, fundus autofluorescence, and infrared reflectance. Copyright © 2014 American Academy of Optometry

Collaborative care of non-urgent macular disease: a study of inter-optometric referrals

PURPOSE: Diseases involving the macula and posterior pole are leading causes of visual impairment and blindness worldwide and may require prompt ophthalmological care. However, access to eye-care and timely patient management may be limited due to inefficient and inappropriate referrals between primary eye-care providers and ophthalmology. Optometrists with a special interest in macular disease may be useful as a community aid to better stratify and recommend best-practice management plans for suitable patients. This study assesses such a notion by appraising the optometric referral patterns of patients with suspected macular disease to an intermediate-tier optometric imaging clinic. METHODS: We performed a retrospective review of patient records and referrals using patients examined at Centre for Eye Health (CFEH) for an initial or follow up macular assessment between the 1/7/2013 and 30/6/2014 (n = 291). The following data were analysed: patient demographic characteristics, primary reason for referral, diagnosed/suspected condition, CFEH diagnosis and recommended management plan. RESULTS: The number of referrals stipulating a diagnosis, confirmed after evaluation at CFEH was 121 of 291 (42%). After evaluation at CFEH, the number of cases without a specific diagnosis was approximately halved (reduced from 47% to 23%), while the number of cases with no apparent defect or normal aging changes rose from 1% to 15%. Overall diagnostic congruency for specified macular conditions was high (58-94%); cases were seldom (30/291, 10%) found to have a completely different macular condition. 244 of 291 (84%) patients seen at CFEH were recommended ongoing optometric care: either with the referring optometrist or through recall to CFEH. Referral to an ophthalmologist was recommended in 47 instances (16%). CONCLUSIONS: More widespread adoption of intermediate-tier optometric eye-care referral pathways in macular disease (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with a diagnosis of normal aging changes or no apparent disease. The majority of cases seen under this intermediate-tier model required ongoing optometric care only and did not require face-to-face consultation with an ophthalmologist