Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task

Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 %?±?19 vs. 92 %?±?9, p?=?0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p?<?0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p?<?0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p?<?0.001), with a trend towards precuneus activation (p?=?0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.     

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m². In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m² higher eGFR at levels below 45 mL/min/1.73 m² was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m². In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.     

Association Between Ankle Fractures and Obesity

Obesity is an epidemic in the United States and is associated with an increased risk of musculoskeletal problems. Rotational injuries of the ankle with a Weber C fibula fracture have a greater risk of syndesmosis disruption and instability. The goal of the present study was to explore the association between obesity and ankle fractures. Using a retrospective review, the radiographs of 280 patients with an ankle fracture were reviewed and classified using the Weber classification, which was then associated with the body mass index, gender, age, diabetes, tobacco use, and osteoporosis. Patients with a body mass index of 30 kg/m² or greater (odds ratio 1.78), men (odds ratio 1.74), and age 25 years or younger (odds ratio 3.97) had greater odds of having a Weber C ankle fracture (compared with Weber A and B) and Weber C and B (compared with Weber A). Diabetes mellitus, osteoporosis/osteopenia, and current tobacco use were not significantly associated with the severity of the ankle fracture. The results from the present study suggest that obesity presents a greater risk of sustaining a more proximal distal fibula fracture.     

The expanding family of hypophosphatemic syndromes

Investigation of X-linked hypophosphatemia (XLH) has led to the identification of a novel phosphate-regulating homeostatic system. Initially considered vitamin D-refractory rickets, renal phosphate wasting was identified as the cardinal biochemical feature of XLH and several related disorders. Current therapy employs calcitriol and phosphate, which usually improves, but does not completely heal deformities and short stature. Later complications of XLH include development of osteophytes, entheses, and osteoarthritis. The mutated gene in XLH, PHEX, is expressed in osteocytes, but its role in the pathogenesis of phosphate wasting is poorly understood. Many hypophosphatemic disorders are mediated by FGF23, a unique fibroblast growth factor with endocrine properties. Renal action of FGF23 leads to reduced expression of type II sodium-phosphate co-transporters, as well as reduced expression of CYP27B1, which encodes vitamin D 1α-hydroxylase. FGF23-mediated hypophosphatemia is characterized by inappropriately normal circulating 1,25-dihydroxyvitamin D together with renal phosphate wasting. The FGF23 system serves as a novel mechanism by which the mineralizing skeleton can communicate phosphate supply to the kidney and thereby mediate excretion or conservation of this important skeletal component. Other forms of FGF23-mediated hypophosphatemia represent various aberrations in this axis. Secretion of excess FGF23 (as in tumor-induced osteomalacia), and mutations preventing proteolytic cleavage of FGF23 result in similar clinical features. Other hypophosphatemic disorders are discussed.     

One-year pivotal trial outcomes of the Nellix system for endovascular aneurysm sealing

Objective

The Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) treatment whereby polymer is used to fill the AAA sac. We report 1-year results of the investigational device exemption pivotal trial.

Scientific Presentation Award: The impact of magnetic resonance imaging on surgical treatment of invasive breast cancer

Background

The purpose of this study was to examine the relationship between magnetic resonance imaging (MRI) and surgical treatment of invasive breast cancer (IBC).

Method

The IBC patients treated from January 2003-June 2008 were reviewed by a single institution.

Results

A total of 814 patients were treated, out of which 562 (69%) underwent breast conservation therapy (BCT), 151 (19%) chose mastectomy alone (M), and 101 (12%) chose mastectomy with reconstruction (M+ R). The mean age was comparatively low in M + R patients (P ≤ 0.001). The mean tumor size was the lowest in BCT patients (P ≤ 0.001). MRI use increased with no significant difference in type of surgery as noted by year. In multivariate analysis, type of surgery was significantly associated with tumor size, multifocality, age, and MRI use. The factors associated with MRI performance were: multifocality, younger age, tumor size, lobular histology, body mass index, and genetic testing.

Conclusions

The use of MRI in IBC patients has increased over the past 5 years, without any observable impact on surgical treatment. Similar factors are associated with mastectomy and MRI performance.     

Does magnetic resonance imaging accurately predict residual disease in breast cancer?

Background

The accuracy of magnetic resonance imaging (MRI) in identifying residual disease after breast conservation therapy (BCT) is unclear.

Method

Review of an institutional database identified patients with positive or close (≤2 mm) margins undergoing MRI before re-excision. Histopathologic correlation was performed.

Results

Forty-three women underwent MRI after BCT. MRI suggested residual disease in 29 patients, of whom 20 (69%) had residual carcinoma pathologically. Nine patients had false-positive MRI as seen by benign pathology findings. Fourteen MRIs indicated no residual disease, of which 6 had residual disease pathologically. The sensitivity and positive predictive value of MRI was 77% and 69%, respectively. MRI conducted within 28 days of the original surgery was 85% sensitive. MRI performed after 28 days was 69% sensitive.

Conclusions

MRI is able to detect residual disease among most patients undergoing re-excision. False-positive results may be caused by inflammatory processes that resemble residual disease.     

CT‐Guided Wire Localization for Involved Axillary Lymph Nodes After Neo‐adjuvant Chemotherapy in Patients With Initially Node‐Positive Breast Cancer

Resection of biopsy‐proven involved axillary lymph nodes (iALNs) is important to reduce the false‐negative rates of sentinel lymph node (SLN) biopsy after neo‐adjuvant chemotherapy (NAC) in patients with initially node‐positive breast cancer. Preoperative wire localization for iALNs marked with clips placed during biopsy is a technique that may help the removal of iALNs after NAC. However, ultrasound (US)‐guided localization is often difficult because the clips cannot always be reliably visible on US. Computed tomography (CT)‐guided wire localization can be used; however, to date there have been no reports on CT‐guided wire localization for iALNs. The aim of this study was to describe a series of patients who received CT‐guided wire localization for iALN removal after NAC and to evaluate the feasibility of this technique. We retrospectively analyzed five women with initially node‐positive breast cancer (age, 41–52 years) who were scheduled for SLN biopsy after NAC and received preoperative CT‐guided wire localization for iALNs. CT visualized all the clips that were not identified on post‐NAC US. The wire tip was deployed beyond or at the target, with the shortest distance between the wire and the index clip ranging from 0 to 2.5 mm. The total procedure time was 21–38 minutes with good patient tolerance and no complications. In four of five cases, CT wire localization aided in identification and resection of iALNs that were not identified with lymphatic mapping. Residual nodal disease was confirmed in two cases: both had residual disease in wire‐localized lymph nodes in addition to SLNs. Although further studies with more cases are required, our results suggest that CT‐guided wire localization for iALNs is a feasible technique that facilitates identification and removal of the iALNs as part of SLN biopsy after NAC in situations where US localization is unsuccessful.     

Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: effects of yohimbine and naloxone

CRH neurons projecting from the paraventricular nucleus (PVN) of the hypothalamus to the median eminence control hypothalamic-pituitary-adrenal (HPA) axis activity. However, CRH neurons outside the PVN as well as PVN neurons projecting to sites other than the median eminence also contribute to the stress response and may play a role in mood and anxiety disorders. We have attempted to investigate possible noradrenergic and opioid regulation of these non-HPA CRH neurons. We hypothesized that yohimbine (an alpha2-adrenergic antagonist) would have stimulatory action on non-HPA CRH neurons, whereas naloxone (a mu-opioid receptor antagonist) would not have this effect. Adult normal volunteers received i.v. yohimbine (n = 5; 0.4 microg/kg), naloxone (n = 4; 125 microg/kg), or placebo (n = 3; 0.9% saline). Cerebrospinal fluid (CSF) was collected continuously, and concentrations of CSF CRH, CSF norepinephrine (NE), and plasma cortisol were measured. Administration of either yohimbine or naloxone caused significant increases in plasma cortisol concentrations over time. Although yohimbine robustly increased CSF NE levels and appeared to increase CSF CRH levels, these effects were not seen after naloxone or placebo administration. Intraindividual correlations were not observed between the measured concentrations of plasma cortisol and CSF CRH for any of the subjects. The results support the idea that CSF CRH concentrations reflect the activity of non-HPA CRH neurons. Although both yohimbine and naloxone stimulated the HPA axis, only yohimbine appeared to have stimulatory effects on central NE and non-HPA CRH.