Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye

BACKGROUND: Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy. METHODS: A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only. RESULTS: Patients were followed up for a median of 61 months (mean: 66, range: 14-156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case. CONCLUSION: Group D patients' families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease

Primary intravenous chemotherapy for group D retinoblastoma: a 13-year retrospective analysis.

BACKGROUND: Eye salvage rate for group D retinoblastoma using intravenous chemotherapy (IVC) as a primary modality is <50%. To report on 13 years' experience with the use of primary IVC for group D retinoblastoma. METHODS: A retrospective analysis of 64 group D eyes (52 patients) treated with primary IVC, from 2002 to 2014. RESULTS: The median age at presentation was 11.0 months (mean: 18.6, range: 0.6-144.0), 35 (67%) patients had bilateral disease, 38 (73%) germline disease and 8 (15%) cases were familial. In addition to IVC, patients received a median number of three treatments (mean: 6, range: 0-24), including thermotherapy/cryotherapy, plaque radiotherapy, intra-ophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy. External beam radiotherapy (EBRT) was used in five eyes, all of which were eventually enucleated. In a median follow-up time of 55 months (mean: 64, range: 14-156), 63% of eyes were salvaged. By the Kaplan-Meier survival analysis, globe salvage rate was 83%, 70%, 59% and 45% at 1, 3, 5 and 10 years, respectively. There were no cases of metastatic spread from intraocular retinoblastoma and no deaths. IVC-related adverse events included febrile neutropenia in 21 (40%) patients and anaphylactic reaction to carboplatin in 2 (4%), all conservatively resolved. Of the patients receiving IAC, third and sixth nerve palsies were documented in two (10%) and one (5%) eyes, respectively. CONCLUSIONS: Primary IVC for group D eyes, with adjuvant treatments as required, was found to be a safe and efficient approach, achieving 63% eye salvage rate, no metastatic spread from intraocular retinoblastoma and no deaths. IAC has now replaced EBRT as a successful salvage treatment

Reduction of seafood processing wastewater using technologies enhanced by swim–bed technology

The increasing growth of the seafood processing industries considerably requires more industrial process activities and water consumption. It is estimated that approximately 10–40 m3 of wastewater is generated from those industries for processing one-tonne of raw materials. Due to limitations and regulations in natural resources utilization, a suitable and systematic wastewater treatment plant is very important to meet rigorous discharge standards. As a result of food waste biodegradability, the biological treatment and some extent of swim-bed technology, including a novel acryl-fibre (biofilm) material might be used effectively to meet the effluent discharge criteria. This chapter aims to develop understanding on current problems and production of the seafood wastewater regarding treatment efficiency and methods of treatment

Results from PAMELA, ATIC and FERMI : Pulsars or Dark Matter ?

It is well known that the dark matter dominates the dynamics of galaxies and clusters of galaxies. Its constituents remain a mystery despite an assiduous search for them over the past three decades. Recent results from the satellite-based PAMELA experiment detect an excess in the positron fraction at energies between 10-100 GeV in the secondary cosmic ray spectrum. Other experiments namely ATIC, HESS and FERMI show an excess in the total electron (\ps + \el) spectrum for energies greater 100 GeV. These excesses in the positron fraction as well as the electron spectrum could arise in local astrophysical processes like pulsars, or can be attributed to the annihilation of the dark matter particles. The second possibility gives clues to the possible candidates for the dark matter in galaxies and other astrophysical systems. In this article, we give a report of these exciting developments.Comment: 27 Pages, extensively revised and significantly extended, to appear in Pramana as topical revie

Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves

Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines

Parental experiences of supporting children with clinically significant post-traumatic distress: a qualitative study of families accessing psychological services

The aim of this study was to investigate the experiences of parents in providing support to their child following trauma exposure in cases where children are experiencing clinically significant levels of post-traumatic distress. Qualitative interviews were conducted with parents whose child was exposed to a trauma and referred for psychological treatment. Parents reported considerable anxiety in coping with their child’s post-traumatic distress. Avoidance of trauma-related discussions was encouraged due to concerns that non-avoidant approaches may worsen children’s post-trauma difficulties. Nonetheless, parents were often sensitive to their child’s distress and offered reassurance and other forms of support. Many barriers existed to accessing psychological treatment, and perceptions of inadequate guidance from therapists on supporting child adjustment contributed to parental distress. The results illustrate the strategies used by parents in supporting their child post-trauma and may assist mental health professionals in providing acceptable guidance to parents following child trauma

Potent and selective chemical probe of hypoxic signaling downstream of HIF-α hydroxylation via VHL inhibition

Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling

Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence

Background: There is scepticism about health effects of dairy products in the public, which is reflected in an increasing intake of plant-based drinks, for example, from soy, rice, almond, or oat. Objective: This review aimed to assess the scientific evidence mainly from meta-analyses of observational studies and randomised controlled trials, on dairy intake and risk of obesity, type 2 diabetes, cardiovascular disease, osteoporosis, cancer, and all-cause mortality. Results: The most recent evidence suggested that intake of milk and dairy products was associated with reduced risk of childhood obesity. In adults, intake of dairy products was shown to improve body composition and facilitate weight loss during energy restriction. In addition, intake of milk and dairy products was associated with a neutral or reduced risk of type 2 diabetes and a reduced risk of cardiovascular disease, particularly stroke. Furthermore, the evidence suggested a beneficial effect of milk and dairy intake on bone mineral density but no association with risk of bone fracture. Among cancers, milk and dairy intake was inversely associated with colorectal cancer, bladder cancer, gastric cancer, and breast cancer, and not associated with risk of pancreatic cancer, ovarian cancer, or lung cancer,while the evidence for prostate cancer risk was inconsistent.Finally,consumption of milk and dairy products was not associated with all-cause mortality. Calcium-fortified plant-based drinks have been included as an alternative to dairy products in the nutrition recommendations in several countries. However, nutritionally, cow’s milk and plant-based drinks are completely different foods,and an evidence-based conclusion on the health value of the plant-based drinks requires more studies in humans. Conclusion: The totality of available scientific evidence supports that intake of milk and dairy products contribute to meet nutrient recommendations, and may protect against the most prevalent chronic diseases, whereas very few adverse effects have been reported

Long-term Visual Acuity, Strabismus, and Nystagmus Outcomes Following Multimodality Treatment in Group D Retinoblastoma Eyes

PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral center. DESIGN: Retrospective interventional case series. METHODS: A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analyzed, and rate of strabismus and nystagmus at last follow-up visit were calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to our center during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 ± 0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT, and tumor-foveola distance (at last visit) were found to be significant risk factors for worse VA (P < .026). On multivariate analysis, however, only TTT was found to be significant (P = .010). At last visit, 6 of 27 (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision; 60% had strabismus; and 22% had nystagmus

Anti-seizure medication tapering correlates with daytime delta band power reduction in the cortex

\ua9 The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. Anti-seizure medications are the primary treatment for epilepsy; yet medication tapering effects have not been investigated in a dose, region and time-dependent manner, despite their potential impact on research and clinical practice. We examined over 3000 h of intracranial EEG recordings in 32 subjects during long-term monitoring, of which 22 underwent concurrent anti-seizure medication tapering. We estimated anti-seizure medication plasma levels based on known pharmaco-kinetics of all the major anti-seizure medication types. We found an overall decrease in the power of delta band (δ) activity around the period of maximum medication withdrawal in most (80%) subjects, independent of their epilepsy type or medication combination. The degree of withdrawal correlated positively with the magnitude of δ power decrease. This dose-dependent effect was evident across all recorded cortical regions during daytime; but not in subcortical regions, or during night time. We found no evidence of a differential effect in seizure onset, spiking, or pathological brain regions. The finding of decreased δ band power during anti-seizure medication tapering agrees with previous literature. Our observed dose-dependent effect indicates that monitoring anti-seizure medication levels in cortical regions may be feasible for applications such as medication reminder systems, or closed-loop anti-seizure medication delivery systems. Anti-seizure medications are also used in other neurological and psychiatric conditions, making our findings relevant to a general neuroscience and neurology audience