In utero exposure to breast cancer treatment: a population-based perinatal outcome study

© 2019, Cancer Research UK. Chemotherapy during a viable pregnancy may be associated with adverse perinatal outcomes. We conducted a prospective cohort study to examine the perinatal outcomes of babies born following in utero exposure to chemotherapy in Australia and New Zealand. Over 18 months we identified 24 births, of >400 g and/or >20-weeks’ gestation, to women diagnosed with breast cancer in the first or second trimesters. Eighteen babies were exposed in utero to chemotherapy. Chemotherapy commenced at a median of 20 weeks gestation, for a mean duration of 10 weeks. Twelve exposed infants were born preterm with 11 by induced labour or pre-labour caesarean section. There were no perinatal deaths or congenital malformations. Our findings show that breast cancer diagnosed during mid-pregnancy is often treated with chemotherapy. Other than induced preterm births, there were no serious adverse perinatal outcomes

Effectiveness of storage as a point-of-use means of improving the bacteriological quality of drinking water

The evaluation of the effectiveness of storage as a point-of-use means for improving the bacteriological quality of drinking water was carried out using a completely randomized block design. Total plate and total coliform counts were enumerated for day 0 -10 samples using Nutrient Agar (NA) and multiple tube techniques respectively. Physicochemical analyses of water samples were carried out using standard procedures including titrimetric methods. Ten bacteria species including Escherichia coli, Bacillus cereus, Citrobacter freundil, Salmonella typhymurium, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Arizona spp., Proteus vulgaris, Enterobacter aerogenes were isolated from water samples obtained from borehole, well and sachet water samples in the study area. For day zero samples, it was found that the total bacteria counts ranged from 1.01x102 to 4.38 x102 CFU/mL for borehole, 0.57x102 to 2.13x102 CFU/mL for well and 0.54x102 to 0.92x102 CFU/mL for sachet water. A significant reduction in bacteria load was recorded for all samples from day 2 to day 7 when the water samples were monitored over a period of ten days. The results reveal that water storage for 2-7 days is a viable point-of-use method of household level drinking water disinfection. © 2013 International Formulae Group. All rights reserved.Keywords: Nigerian Institute of Standards, Coliforms, water storage, E.coli

Schizophrenia syndrome due to C9ORF72 mutation case report: a cautionary tale and role of hybrid brain imaging!

Background: Frontal variant frontotemporal dementia is a common cause of presenile dementia. A hexanucleotide expansion on chromosome 9 has recently been recognized as the most common genetic mutation cause of this illness. This sub-type tends to present psychiatrically with psychosis being a common presenting symptom before the onset of cognitive changes or brain atrophy. A few case series have been published describing the prominence of early psychotic symptoms, and lack of clear brain atrophy on clinical brain imaging imposing a challenge in reaching early accurate diagnosis. In this report, we present a case whereby the diagnosis of Schizophrenia syndrome was made and the patient was treated for years with multiple interventions for that syndrome before reaching the accurate diagnosis of Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9. This diagnosis was confirmed after genetic testing and findings on a hybrid Positron Emission Tomography/Magnetic Resonance Imaging scanning. Case summary: A 60-year-old female diagnosed with schizophrenia at age 50 after presenting with delusions and hallucinations, which proved to be refractor to several lines of pharmacological and non-pharmacological interventions including electroconvulsive therapy. Patient had a history of post-partum psychosis in her 20s. She was referred to cognitive neurology due to progressive decline in function. While clinical structural brain imaging data were not adequate to support an alternative neurological diagnosis, careful inquiry elicited a history of psychotic illness followed by progressive decline in a sister. Genetic testing confirmed hexanucleotide expansion on chromosome 9 mutation. The patient was offered a state-of-the-art FD-Glucose Positron Emission Tomography/Magnetic Resonance Imaging scan available at our centre. While volumetric Magnetic Resonance Imaging scan did not show volume loss in frontotemporal areas, the hybrid scan showed regionally specific deficit in FD-Glucose Positron Emission Tomography affecting medial superior frontal, insula, inferior temporal, thalamus, and anterior cingulate cortex consistent with behavioral variant frontotemporal dementia. Conclusions: This case highlights the importance of considering Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9 when facing relatively late-onset, refractory schizophrenia-like syndrome. Careful history from all available sources to elicit family history of similar presentation is very important. Genetic testing and functional brain imaging can aid in confirming the diagnosis and potentially streamlining the management of these cases

Multimodal Measurements of Brain Tissue Metabolism and Perfusion in a Neonatal Model of Hypoxic-Ischaemic Injury

This is the first multimodal study of cerebral tissue metabolism and perfusion post-hypoxic-ischaemic (HI) brain injury using broadband near-infrared spectroscopy (bNIRS), diffuse correlation spectroscopy (DCS), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). In seven piglet preclinical models of neonatal HI, we measured cerebral tissue saturation (StO2), cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), changes in the mitochondrial oxidation state of cytochrome c oxidase (oxCCO), cerebral glucose metabolism (CMRglc) and tissue biochemistry (Lac+Thr/tNAA). At baseline, the parameters measured in the piglets that experience HI (not controls) were 64 ± 6% StO2, 35 ± 11 ml/100 g/min CBF and 2.0 ± 0.4 μmol/100 g/min CMRO2. After HI, the parameters measured were 68 ± 6% StO2, 35 ± 6 ml/100 g/min CBF, 1.3 ± 0.1 μmol/100 g/min CMRO2, 0.4 ± 0.2 Lac+Thr/tNAA and 9.5 ± 2.0 CMRglc. This study demonstrates the capacity of a multimodal set-up to interrogate the pathophysiology of HIE using a combination of optical methods, MRS, and PET

Gestational breast cancer in New South Wales: A population-based linkage study of incidence, management, and outcomes.

BackgroundThe incidence of gestational breast cancer (GBC) is increasing in high-income countries. Our study aimed to examine the epidemiology, management and outcomes of women with GBC in New South Wales (NSW), Australia.MethodsA retrospective cohort study using linked data from three NSW datasets. The study group comprised women giving birth with a first-time diagnosis of GBC while the comparison group comprised women giving birth without any type of cancer. Outcome measures included incidence of GBC, maternal morbidities, obstetric management, neonatal mortality, and preterm birth.ResultsBetween 1994 and 2013, 122 women with GBC gave birth in NSW (crude incidence 6.8/ 100,000, 95%CI: 5.6-8.0). Women aged ≥35 years had higher odds of GBC (adjusted odds ratio (AOR) 6.09, 95%CI 4.02-9.2) than younger women. Women with GBC were more likely to give birth by labour induction or pre-labour CS compared to women with no cancer (AOR 4.8, 95%CI: 2.96-7.79). Among women who gave birth by labour induction or pre-labour CS, the preterm birth rate was higher for women with GBC than for women with no cancer (52% vs 7%; AOR 17.5, 95%CI: 11.3-27.3). However, among women with GBC, preterm birth rate did not differ significantly by timing of diagnosis or cancer stage. Babies born to women with GBC were more likely to be preterm (AOR 12.93, 95%CI 8.97-18.64), low birthweight (AOR 8.88, 95%CI 5.87-13.43) or admitted to higher care (AOR 3.99, 95%CI 2.76-5.76) than babies born to women with no cancer.ConclusionWomen aged ≥35 years are at increased risk of GBC. There is a high rate of preterm birth among women with GBC, which is not associated with timing of diagnosis or cancer stage. Most births followed induction of labour or pre-labour CS, with no major short term neonatal morbidity

Patterns and Predictors of Healthcare Use among Adolescent and Young Adult Cancer Survivors versus a Community Comparison Group.

Healthcare use (HCU) during survivorship can mitigate adolescent and young adult (AYA) cancer survivors' (aged 15-39 years) risk of medical and psychosocial late effects, but this is understudied. We surveyed 93 Australian AYA post-treatment cancer survivors (Mage = 22.0 years, SD = 3.5; 55.9% female) and a comparison sample of 183 non-matched AYAs (Mage = 19.7, SD = 3.2; 70.5% female) on their HCU, medication use, depression/anxiety, and general functioning. Relative to our comparison AYAs, a higher proportion of our survivor group reported medical HCU (community-delivered: 65.6% versus 47.0%, p = 0.003; hospital-delivered: 31.2% versus 20.3%, p = 0.044) and mental HCU (53.8% vs. 23.5%; p < 0.0001) in the past six months. A higher proportion of our survivors reported taking medications within the past six months than our comparison AYAs (61.3% vs. 42.1%, p = 0.003) and taking more types (p < 0.001). Vitamin/supplement use was most common followed by psychotropic medications. Our survivor group reported lower depression (p = 0.001) and anxiety symptoms (p = 0.003), but similar work/study participation (p = 0.767) to our comparison AYAs. Across groups, psychological distress was associated with higher mental HCU (p = 0.001). Among survivors, those who were female, diagnosed with brain/solid tumors and who had finished treatment more recently reported greater HCU. Future research should establish whether this level of HCU meets AYAs' survivorship needs

A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma

NUT midline carcinoma (NMC) is a fatal cancer that arises in various tissues along the upper midline of the body. The defining molecular feature of NMC is a chromosomal translocation that joins (in the majority of cases) the nuclear testis gene NUT (NUTM1) to the bromodomain protein family member 4 (BRD4) and thereby creating a fusion oncogene that disrupts cellular differentiation and drives the disease. In this study, we report the case of an adolescent NMC patient presenting with severe facial pain, proptosis and visual impairment due to a mass arising from the ethmoid sinus that invaded the right orbit and frontal lobe. Treatment involved radical resection, including exenteration of the affected eye with the view to consolidate treatment with radiation therapy; however, the patient experienced rapid tumor progression and passed away 79 days post resection. Molecular analysis of the tumor tissue identified a novel in-frame BRD4-NUT transcript, with BRD4 exon 15 fused to the last 124 nucleotides of NUT exon 2 (BRD4-NUT ex15:ex2Δnt1–585). The partial deletion of NUT exon 2 was attributed to a mid-exonic genomic breakpoint and the subsequent activation of a cryptic splice site further downstream within the exon. Inhibition of the canonical 3′ acceptor splice site of NUT intron 1 in cell lines expressing the most common NMC fusion transcripts (PER-403, BRD4-NUT ex11:ex2; PER-624, BRD4-NUT ex15:ex2) induced alternative splicing from the same cryptic splice site as identified in the patient. Detection of low levels of an in-frame BRD4-NUT ex11:ex2Δnt1–585 transcript in PER-403 confirmed endogenous splicing from this alternative exon 2 splice site. Although further studies are necessary to assess the clinical relevance of the increasing number of variant fusions described in NMC, the findings presented in this case identify alternative splicing as a mechanism that contributes to this pathogenic complexity