Neuroendocrine morbidity after pediatric optic gliomas: a longitudinal analysis of 166 children over 30 years

Context: 50% of pediatric low-grade gliomas affect the optic pathway, hypothalamus and suprasellar areas (OP/HSGs) resulting in significant long-term neuroendocrinopathy. Objective: To dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy. Design: Retrospective case notes analysis of 166 children with newly-diagnosed OP/HSGs at our quaternary center between 1980 –2010 by multivariate Cox, linear and logistic regression. Results: Patients were of median (range) age 4.9 (0.2–15.4) years at diagnosis and followed up for 8.3 (0.04 –26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free (EEFS) survival were 47.2% and 20.8% respectively. EEFS declined up to 15 years postdiagnosis, with hypothalamic involvement (p0.001) being implicated more than radiotherapy (p0.008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy p0.001; hypothalamic involvement p0.006). GH deficiency (GHD) was commonest (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD, 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (p0.01), but replacement did not increase progression. CPP was associated with future GnD (p0.05). Posterior pituitary dysfunction (PPD, 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths. 50.2% became obese. Tumor extent, surgery and increased endocrinopathy, rather than radiotherapy, predicted visuo-cognitive morbidity. Conclusions: This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whilst life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival

The utility of brain biopsy in pediatric cryptogenic neurological disease

OBJECTIVE: The authors’ aim was to characterize a single-center experience of brain biopsy in pediatric cryptogenic neurological disease. METHODS: The authors performed a retrospective review of consecutive brain biopsies at a tertiary pediatric neurosciences unit between 1997 and 2017. Children < 18 years undergoing biopsy for neurological pathology were included. Those with presumed neoplasms and biopsy performed in the context of epilepsy surgery were excluded. RESULTS: Forty-nine biopsies in 47 patients (25 females, mean age ± SD 9.0 ± 5.3 years) were performed during the study period. The most common presenting symptoms were focal neurological deficit (28.6%) and focal seizure (26.5%). Histopathological, microbiological, and genetic analyses of biopsy material were contributory to the diagnosis in 34 cases (69.4%). Children presenting with focal seizures or with diffuse (> 3 lesions) brain involvement on MRI were more likely to yield a diagnosis at biopsy (OR 3.07 and 2.4, respectively). Twelve patients were immunocompromised and were more likely to yield a diagnosis at biopsy (OR 6.7). Surgery was accompanied by severe complications in 1 patient. The most common final diagnoses were infective (16/49, 32.7%), followed by chronic inflammatory processes (10/49, 20.4%) and occult neoplastic disease (9/49, 18.4%). In 38 cases (77.6%), biopsy was considered to have altered clinical management. CONCLUSIONS: Brain biopsy for cryptogenic neurological disease in children was contributory to the diagnosis in 69.4% of cases and changed clinical management in 77.6%. Biopsy most commonly revealed underlying infective processes, chronic inflammatory changes, or occult neoplastic disease. Although generally safe, the risk of severe complications may be higher in immunocompromised and myelosuppressed children

Fourth ventricle tumors in children: complications and influence of surgical approach

OBJECTIVES: The goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors. / METHODS: All patients referred to the authors’ institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications. / RESULTS: Three hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment. Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach. / CONCLUSIONS: Surgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials—Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups

Safety and efficacy of aluminosilicate of sodium, potassium, calcium and magnesium as a feed additive for pigs

Following a request from the European Commission, the Panel&nbsp;on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on aluminosilicate of sodium, potassium, calcium and magnesium as a feed additive for pigs. The additive, that contains at least 66% of aluminosilicate of sodium, potassium, calcium and magnesium as main component, is intended for use as a technological additive (functional groups: (i) anticaking agents) in premixtures and feedingstuffs for pigs at a maximum inclusion level of 30,000&nbsp;mg/kg. In the absence of data, the FEEDAP Panel&nbsp;could not conclude on the safety of the additive for the target species and the users. The additive is considered safe for the consumer and the environment at the proposed conditions of use. The additive has the potential to act as an anticaking agent in complete feed of pigs at a concentration of 30,000&nbsp;mg/kg feed

Assessment of the application for renewal of authorisation of PHYZYME&#174; XP 5000 G/L (6-phytase) for chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, weaned piglets, pigs for fattening and sows for reproduction

PHYZYME\uae XP 5000 G/L is a feed additive that contains 6-phytase produced by a genetically modified strain of Schizosaccharomyces&nbsp;pombe. The applicant requested for the renewal of the authorisation for PHYZYME\uae XP 5000 G and L to be used as a feed additive in chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, piglets (weaned), pigs for fattening and sows. This scientific opinion concerns the renewal of the authorisation of the additive for those species. To support the request, the applicant provided evidence that the additive in the market complies with the conditions of the authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the FEEDAP Panel&nbsp;reconsider the previous conclusions regarding the safety for the target species, consumer, user and environment. The application for renewal of the authorisation did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation

Dementia and detectives: Alzheimer's disease in crime fiction

Fictional representations of dementia have burgeoned in recent years, and scholars have amply explored their double-edged capacity to promote tragic perspectives or normalising images of ‘living well’ with the condition. Yet to date, there has been only sparse consideration of the treatment afforded dementia within the genre of crime fiction. Focusing on two novels, Emma Healey’s Elizabeth is Missing and Alice LaPlante’s Turn of Mind, this article considers what it means in relation to the ethics of representation that these authors choose to cast as their amateur detective narrators women who have dementia. Analysing how their narrative portrayals frame the experience of living with dementia, it becomes apparent that features of the crime genre inflect the meanings conveyed. While aspects of the novels may reinforce problem-based discourses around dementia, in other respects they may spur meaningful reflection about it among the large readership of this genre

Safety and efficacy of lutein and lutein/zeaxanthin extracts from Tagetes&#160;erecta for poultry for fattening and laying (except turkeys)

The Panel&nbsp;on Additives and Products or Substances used in Animal Feed (FEEDAP) evaluated (i) lutein from a saponified extract from Tagetes&nbsp;erecta obtained via extraction and saponification (lutein not less than 85% of total carotenoids (TC)) and (ii) lutein/zeaxanthin extract from Tagetes&nbsp;erecta obtained via extraction, saponification and isomerisation (lutein not less than 45% and zeaxanthin not less than 35% of TC). The maximum proposed use level of 80&nbsp;mg&nbsp;TC from saponified Tagetes extract/kg complete feed for chickens for fattening and laying hens is safe for these animal categories. This conclusion can be extrapolated to minor poultry species for fattening and laying. The conclusions on saponified Tagetes extract for poultry for fattening and laying are extended to the saponified/isomerised Tagetes extract. The maximum use level of the saponified/isomerised Tagetes extract in breeding minor poultry should not exceed 50&nbsp;mg&nbsp;TC/kg feed, considering the toxicological potential of zeaxanthin on reproduction. The saponified Tagetes extract is not genotoxic. This conclusion is extended to the saponified/isomerised Tagetes extract. Consumer exposure related to the consumption of animal products is very low compared to the exposure from other sources. The active substance is a viscous paste and may be irritant to skin and eyes; no exposure by inhalation is expected. In the absence of data, the Panel&nbsp;cannot conclude on the safety for the user of commercial preparations. The use of Tagetes extracts in poultry feed raised no concern for the environment. Tagetes extracts at levels up to the proposed maximum use level of 80&nbsp;mg&nbsp;TC/kg complete feed have the potential to colour the egg yolk of laying hens and the skin of chickens for fattening. This conclusion is extended to minor poultry species for laying and for fattening. The use of the additive in feed and water for drinking is considered bioequivalent

Assessment of the application for renewal of the authorisation of Natuphos (3-phytase) as a feed additive for poultry and pigs

Natuphos \uae is a feed additive that contains 3-phytase which is produced \u25a0\u25a0\u25a0\u25a0\u25a0 The product is currently authorised for use as a feed additive in chickens for fattening, piglets (weaned) and pigs for fattening, laying hens and turkeys for fattening, ducks, sows, all minor avian species other than ducks and ornamental birds. This scientific opinion concerns the renewal of the authorisation of this additive for those species. The application also included chickens reared for laying/breeding, turkeys reared for breeding and breeding hens. The applicant provided evidence that the additive in the market complies with the conditions of authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the Panel&nbsp;on Additives and Products or Substances used in Animal Feed (FEEDAP) reconsider the previous conclusions regarding the safety for the target species, consumer and environment under the authorised conditions of use. The additive is a respiratory sensitiser and a potential skin sensitiser. The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in for those species for which an authorisation exists. The Panel&nbsp;also considered that the additive is safe and has a potential to be efficacious in chickens reared for laying/breeding, turkeys reared for breeding, breeding hens and suckling piglets at the corresponding recommended doses

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6±14.9 y (52-89 y), with mean radiation dose of 75.0±35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6±1.3×10. 7 cells were obtained. All cases healed uneventfully after 6.6±3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9±0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds