Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer

Background After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. Methods Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. Results SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. Conclusions SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.     

Prevalence and Incidence of Epilepsy in an Elderly and Low-Income Population in the United States

Background and Purpose

The purpose of this study was to estimate the incidence and prevalence of epilepsy among an elderly and poor population in the United States.

Methods

Arizona Medicaid claims data from January 1, 2008 to December 31, 2010 were used for this analysis. Subjects who were aged ≥65 years and were continuously enrolled in any Arizona Medicaid health plans (eligible to patients with low income) for ≥12 months between January 1, 2008 and December 31, 2009 were considered eligible for inclusion in the study cohort. In addition to meeting the aforementioned criteria, incident and prevalent cases must have had epilepsy-related healthcare claims. Furthermore, incident cases were required to have a 1-year "clean" period immediately preceding the index date. Negative binomial and logistic regression models were used to assess the factors associated with epilepsy incidence and prevalence.

Results

The estimated epilepsy incidence and prevalence for this population in 2009 were 7.9 and 19.3 per 1,000 person-years, respectively. The incidence and prevalence rates were significantly higher for patients with comorbid conditions that were potential risk factors for epilepsy and were of younger age than for their non-comorbid and older counterparts (p<0.05). The prevalence rates were significantly higher for non-Hispanic Blacks and male beneficiaries than for non-Hispanic Whites and female beneficiaries, respectively (p<0.05).

Conclusions

This patient population had higher epilepsy incidence and prevalence compared with the general US population. These differences may be at least in part attributable to their low socioeconomic status.     

Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease

Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be inappropriately activated in several neurodegenerative conditions. Here, we report that cdk5 expression and activity are elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that damages the nigrostriatal dopaminergic pathway. Supporting the pathogenic significance of the cdk5 alterations are the findings that the general cdk inhibitor, flavopiridol, or expression of dominant-negative cdk5, and to a lesser extent dominant-negative cdk2, attenuates the loss of dopaminergic neurons caused by MPTP. In addition, CDK inhibition strategies attenuate MPTP-induced hypolocomotion and markers of striatal function independent of striatal dopamine. We propose that cdk5 is a key regulator in the degeneration of dopaminergic neurons in Parkinson's disease.     

Ageing and the small,non-coding RNA world

MicroRNAs, a class of small, non-coding RNAs, are now widely known for their importance in many aspects of biology. These small regulatory RNAs have critical functions in diverse biological events, including development and disease. Recent findings show that microRNAs are essential for lifespan determination in the model organisms, Caenorhabditis elegans and Drosophila, suggesting that microRNAs are also involved in the complex process of ageing. Further, short RNA fragments derived from longer parental RNAs, such as transfer RNA cleavage fragments, have now emerged as a novel class of regulatory RNAs that inhibit translation in response to stress. In addition, the RNA editing pathway is likely to act in the double-stranded RNA-mediated silencing machinery to suppress unfavorable RNA interference activity in the ageing process. These multiple, redundant layers in gene regulatory networks may make it possible to both stably and flexibly regulate genetic pathways in ensuring robustness of developmental and ageing processes.