Effect of Preoperative MRI on Mastectomy and Contralateral Prophylactic Mastectomy rates at a Community Hospital by a Single Surgeon

Magnetic resonance imaging (MRI) use in the preoperative evaluation of newly diagnosed breast cancer (BC) patients is rising. We evaluated MRI as a function of surgical year with respect to mastectomy and contralateral prophylactic mastectomy (CPM) rates by a single surgeon. From January 2000 to December 2010, 1,279 patients with 1,296 breast cancers were identified. Our breast MRI was installed in April 2006. Mastectomy and CPM rates were evaluated by surgical year and stratified as “pre‐MRI” or “MRI” depending on whether surgery occurred before or after April 2006. There was a significant increase in the percentage of patients undergoing MRI in the “pre‐MRI” versus “MRI” era (17.2% versus 78.7%, p < 0.001). In contrast, mastectomy rates decreased with 29.9% undergoing mastectomy before 2006 versus 24.5% after 2006 (p = 0.038). Except for 2007, where CPM rates dropped to 7.1%, CPM rates increased from 16.7% in 2000 to 51.9% in 2010 (p = 0.033). The use of MRI, additional MRI findings and additional MRI biopsies were not associated with the decision for CPM. Age <50 was the only factor associated with CPM (RR = 2.12, p = 0.001). In our community hospital, mastectomy rates have decreased despite the increased use of preoperative MRI. MRI alone may not explain the increasing rates of mastectomy reported in other series. CPM rates have dramatically increased over time, seemingly independent of MRI use. Prospective studies are needed to assess the role of surgeon bias, along with other factors, in surgical decision making.     

Matrix metalloproteinase abundance in human myocardial fibroblasts: effects of sustained pharmacologic matrix metalloproteinase inhibition

BACKGROUND: A cause-effect relationship has been established between matrix metalloproteinases (MMPs) and left ventricular (LV) myocardial remodeling through the use of pharmacologic MMP inhibitors. However, the direct effects of MMP inhibition on MMPs and endogenous tissue inhibitors of metalloproteinases (TIMPs) in LV human myocardial fibroblasts (LVHMFs) remain unknown. This study measured MMP-2, MMP-9, MMP-13, MT1-MMP, and TIMP-1 release in LVHMFs. METHODS AND RESULTS: LVHMF cultures were established from six individual patients (passages 2-5) and incubated with and without the broad-spectrum MMP inhibitor PD166793 (100 microM) for 12-36 h. While PD166793 did not influence MMP-2 release, MMP-9 levels based on substrate zymography increased at 36 h by over 30% (P < 0.05). TIMP-1 levels increased in a time-dependent manner with no effect from PD166793 incubation. However, the MMP-9/TIMP-1 ratio was increased by over 20% from time-matched values following 12-36 h of exposure to PD166793 (P < 0.05). Similar results obtained after incubation of LVHMF cultures with the broad-spectrum MMP inhibitor Batimastat (BB-94) suggest that these observations are due to a general class effect of broad-spectrum MMP inhibitors. CONCLUSIONS: This study is the first to demonstrate that a selective induction and release of an MMP species occurs with sustained exposure to pharmacologic MMP inhibition in LVHMFs. These observations may have particular importance with respect to controlling this proteolytic system in the context of LV myocardial remodeling.     

Impact of Years of Clinical Experience on Perceived Contraindications and Barriers to the Use of LARC: A Survey of Family Planning Providers

BackgroundDespite their efficacy in preventing unintended pregnancies, intrauterine devices (IUDs) are still relatively underutilized by American women. Although cost of these methods is clearly a barrier to use, IUDs have had a long and sometimes controversial history, and earlier versions were removed from the market.MethodsThis study explores the degree to which the length of licensure for providers is related to their attitudes toward or fears about these methods. Data come from a 2012 survey of 114 clinicians in Colorado and Iowa, collected as part of two, statewide initiatives to reduce unintended pregnancy. Providers were asked about service barriers to prescribing these methods and for which patients they perceived them to be suitable and safe.ResultsThe most experienced clinicians were the least concerned about uterine perforation and history of the Dalkon Shield, but were more likely to fear a lawsuit over complications. More experienced clinicians were also less approving of Copper T IUDs for all 11 subgroups of women, including nulliparous women and those with histories of sexually transmitted infections. They were also less approving of hormonal IUDs for 10 groups of women, including those with histories of ectopic pregnancies. However, clinicians with the most recent licensure were more conservative in their approval of single rod implants than were the providers with the most years since licensure.ConclusionsThis paper explores potential reasons for these findings and suggests trainings to recognize and overcome these barriers so as to promote consistent and accurate practice across clinicians, regardless of years of experience.     

Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes

Aim

Fertility post-orchidopexy is dependent on transformation of neonatal gonocytes (G) into adult dark spermatogonia at about 3 months, the same time as gonadotrophins stimulate androgen secretion. We examined how androgen blockade affects transformation of gonocytes to spermatogonial stem cells (SSC) during this period in patients with undervirilisation syndromes.

Methods

Patients with undervirilisation syndromes (n = 30, 1.5 weeks–16 years) underwent review of medical records, pathology reports, and H&E slides of testes (ethics HREC32164). Fluorescent immunohistochemistry against anti-Mullerian hormone (AMH, Sertoli cells), mouse VASA homologue (MVH, germ cells) and DAPI (nuclei) allowed the number of MVH-positive gonocytes/spermatogonial stem cells per seminiferous tubular cross-section (G/T or SSC/T) to be counted.

Results

Gonocytes (MVH-positive cells in the tubular lumen) were present in 15/16 patients under 2 years old. SSC (MVH-positive cells on the tubule basement membrane) were present in 25/30 patients. With increasing age, the mean number of SSC/T decreased from ~ 4 to 0, and G/T decreased from ~ 1.5 to 0. SSC were present in CAIS and PAIS patients at 1.5 and 3.5 weeks old, respectively.

Conclusions

Gonocytes transform into SSC earlier than expected in patients with undervirilisation syndromes. Lack of androgens may stimulate non-androgenic regulators to trigger transformation. Understanding how gonocytes transform may enable optimization of spermatogonial development to preserve fertility post-orchidopexy.     

Cerebellar Loops: A Review of the Nucleocortical Pathway

Feedback pathways are a common circuit motif in vertebrate brains. Reciprocal interconnectivity is seen between the cerebral cortex and thalamus as well as between basal ganglia structures, for example. Here, we review the literature on the nucleocortical pathway, a feedback pathway from the cerebellar nuclei to the cerebellar cortex, which has been studied anatomically but has remained somewhat obscure. This review covers the work examining this pathway on a number of levels, ranging from its existence in numerous species, its organization within cerebellar circuits, its cellular composition, and a discussion of its potential roles in motor control. Recent interest in cerebellar modular organization raises the profile of this neglected cerebellar pathway, and it is hoped that this review will consolidate knowledge gained over several decades of research into a useful format, spurring new investigations into this evolutionarily conserved pathway.