Oral contraceptives and the risk of death from breast cancer

OBJECTIVE: To examine the relationship between the use of oral contraceptives and the risk of death from breast cancer. METHODS: We used interview data from the Cancer and Steroid Hormone Study, linked to cancer registry data from the Surveillance, Epidemiology, and End Results Program, to examine the 15-year survival and prior use of oral contraceptives among 4,292 women aged 20 to 54 years when diagnosed with breast cancer from December 1, 1980, to December 31, 1982. Cox proportional hazard models were used to estimate the relative rate of death from breast cancer by oral contraceptive use. RESULTS: Duration of oral contraceptive use, time since first use, age at first use, and use of specific pill formulations were not associated with survival. For time since last use, the risk of death from breast cancer decreased significantly with increasing time since last use of oral contraceptives, but a consistent gradient effect was not observed. Adjusted hazard ratios ranged from 0.86 to 1.41 and were 1.00 or less for all recency categories except during 13 to 24 months before diagnosis; none was statistically significant. Women who were currently using oral contraceptives had an adjusted hazard ratio of 0.90 (0.68, 1.19). CONCLUSION: Overall, oral contraceptive use had neither a harmful nor a beneficial effect on breast cancer mortality. The differences between pill users and nonusers were slight, and the risk estimates were usually reduced with confidence limits that nearly always included 1.0.     

Microglandular adenosis: a prime suspect in triple‐negative breast cancer development

Microglandular adenosis (MGA) and atypical MGA (AMGA) are unusual lesions of the breast. They were once regarded as benign proliferative lesions and innocent bystanders. Several lines of evidence suggested that they could be neoplastic, clonal lesions and a non‐obligate precursor for triple‐negative breast cancers (TNBC). Recent work published in The Journal of Pathology by Guerini‐Rocco and colleagues provided further evidence regarding the precursor–product relationship between MGA/AMGA and TNBC. Using a massively parallel sequencing approach, they demonstrated that MGA/AMGA, particularly those associated with TNBC, could be clonal neoplastic lesions showing clonal non‐synonymous mutations, but none in pure MGA. Importantly, those alterations were observed in the associated TNBC. They were also able to identify recurrent alterations in TP53 in those MGA/AMGA cases as well as their associated TNBC. The findings, in conjunction with others, underscore the significance for MGA in clinical diagnosis. The potential of a benign lesion to progress into an aggressive malignant tumour implies that modification of the current management approach may be necessary. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice

Although the key event in the pathology of prion diseases is thought to be the conversion of cellular prion protein (PrP(C)) to the protease-resistant scrapie species termed PrP(Sc), the factors that contribute to neurodegeneration in scrapie-infected animals are poorly understood. One probable determinant could be when the accumulation of PrP(Sc) in infected brain overwhelms the ubiquitin-proteasome system and triggers the degenerative cascade. In the present study, it was found that in mouse brains infected with the ME7 scrapie strain, the level of ubiquitin protein conjugates increased significantly at approximately 144 days post-infection (pi) when clinical signs first become apparent. This elevation correlated with the detection of protease-resistant PrP(Sc) and a decline in two endopeptidase activities associated with proteasome function. However, ubiquitination of PrP was only detected at the terminal stage, 3 weeks after the development of clinical symptoms (approximately 165 days pi). These results suggest that ubiquitination of PrP is a late event phenomenon and this conjugation occurs after the formation of protease-resistant PrP(Sc). Whether this post-translational modification and the impairment of proteasome function are pivotal events in the pathogenesis of prion diseases remains to be determined.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Speech-controlled generation of radiology reports

Voice entry has been successfully employed to generate radiology reports with a word recognizer with a 1,000-word lexicon capacity. About 50% of reports were able to be dictated with a single 900-word lexicon. This was split into five sections by anatomic or subspecialty application. Each was augmented to 900 words. By switching from one lexicon to another, it was possible to dictate more than 70% of reports. With exclusive use of three lexicons in subspecialty areas (gastrointestinal radiology, neuroradiology, and mammography), and with further modification of the respective vocabulary, it has been possible to employ the system 88% of the time. Twelve percent of cases included wording that was beyond the scope of the lexicon. Computer subsets that allow different translations of some words when used in different contexts have been used. Some of these are used as triggers that will print whole lines, sentences, or even complete reports. Dictation times with voice entry take about 20% longer. Recognition reliability has been greater than 95%.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

Impact of sickle cell disease and thalassemias in infants on birth outcomes

Objective

The contribution of sickle cell disease (SCD) and other common thalassemias in infants to adverse birth outcomes is under-studied. We therefore sought to compare adverse birth outcomes in infants with and without hemoglobinopathy.

Study design

Retrospective cohort study utilizing a population-based dataset from Florida (1998–2007, n = 1,564,038). The primary outcomes were low birthweight (LBW), very low birthweight (VLBW), preterm birth (PTB), very preterm birth (VPTB) and small for gestational age (SGA). We used propensity scores to match infants with hemoglobinopathy to those without hemoglobinopathy on selected variables. To approximate relative risks, we generated adjusted odds ratios (AOR) and 95% confidence intervals (CI) from logistic regression models and accounted for the matched design using generalized estimating equations framework.

Results

Infants with SCD or thalassemia had a heightened risk for LBW (AOR = 1.58, 95% CI: 1.29–1.93), VLBW (AOR = 3.01, 95% CI: 2.12–4.25), PTB (AOR = 1.36, 95% CI: 1.12–1.65), VPTB (AOR = 2.70, 95% CI: 1.93–3.78), and neurological conditions (AOR = 2.04, 95% CI: 1.48–2.81) compared to infants without hemoglobinopathy.

Conclusion

Infants with SCD or thalassemia experience considerably higher risks for multiple infant morbidities. Our findings are potentially important in prenatal counseling, as well as for targeted care of affected pregnancies in the prenatal period.