Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Determinants of Repeat Curative Intent Surgery in Colorectal Liver Metastasis

Introduction

Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), repeat CIS for recurrence improves survival. The factors associated with repeat CIS are not widely reported.

Methods

An institutional database (January 2002–December 2012) was reviewed to evaluate factors influencing repeat CIS.

Results

One hundred sixty-three patients with colorectal liver metastasis (CRLM) underwent successful CIS. Median follow-up and disease-free interval (DFI) was 33 and 16 months, respectively. After initial CIS, 102 patients (63 %) recurred. Fifty-three patients (52 %) underwent a repeat CIS. After repeat CIS, 33 patients (62 %) developed a second recurrence, and in 13 patients (39 %), a third CIS was possible. DFI decreased following initial CIS (first CIS vs. second CIS vs. third CIS [20 vs. 15 vs. 8.5 months], p?Conclusion Despite high recurrence and decreasing DFI, repeat CIS provides a survival benefit. Postoperative complications, DFI, number, and pattern of recurrence influence the decision to pursue repeat CIS.     

Pathologic Grade and Tumor Size are Associated with Recurrence-Free Survival in Patients with Duodenal Neuroendocrine Tumors

Background

Duodenal neuroendocrine tumors are rare and few studies exist to guide surgical management. This study identifies factors associated with recurrence after resection.

Methods

A retrospective, single institution review was performed between 1983 and 2011 on patients with a pathologic diagnosis of duodenal neuroendocrine tumor. Tumor grade was assigned based on WHO 2010 criteria (Ki-67 and mitotic rate).

Results

Seventy-five patients were identified that underwent curative resection. This included 12 patients with endoscopic mucosal resection, 34 that had local resection, and 29 that underwent pancreaticoduodenectomy. Two-year and 5-year recurrence-free survival was 84 and 81 %, respectively. There were 11 tumor recurrences (either local or distant), and four patients died of their disease (3/4 had high-grade lesions) with an overall median follow-up of 27 months. On univariate analysis, tumor size and tumor grade were identified as being associated with recurrence, but not intervention type, lymph node metastases, ampullary location, or margin status.

Conclusions

Tumor grade and size are associated with recurrence-free survival in duodenal neuroendocrine tumors. When feasible, a less aggressive surgical approach to treat low-grade and low-stage duodenal NETs should be considered.     

A role delineation study of hand surgery in the USA: assessing variations in fellowship training and clinical practice

Background

We examined the fellowship experience of hand surgeons in the USA to identify gaps and variations in exposure to essential skills and knowledge during hand fellowship.

Methods

We conducted a web-based survey of the entire American Society for Surgery of the Hand and American Association for Hand Surgery membership. We inquired about the level of exposure received to 170 knowledge topics and procedures during fellowship. We used factor analysis to group the knowledge topics and procedures into 79 scales of related items and calculated mean exposure ratings for each scale. We compared the ratings between graduates of plastic surgery (PS) and orthopedic surgery (OS) Residency Review Committee (RRC)-accredited fellowships.

Results

Our response rate was 21 % (n?=?562). Plastic surgery RRC-accredited fellowship graduates reported inadequate exposure for proficiency in 22 % (17/79) of the knowledge topic and procedure scales whereas graduates of OS RRC-accredited fellowships reported inadequate exposure for proficiency in 10 % (8/79) of the scales. Moreover, 11 and 21 % of graduates from PS RRC-accredited fellowships reported receiving no exposure in distal radius/ulna and forearm conditions, respectively, whereas only 1 and 2 % of graduates from OS RRC-accredited fellowships reported receiving no exposure in the same domains, respectively.

Conclusions

Hand surgeons reported significant variations in exposure to essential skills and knowledge. Additionally, in a considerable number of knowledge topics and procedures, a majority of participants in both groups reported what they perceived as inadequate or no exposure during their hand surgery fellowship.     

Endophytic species of Colletotrichum associated with mango in northeastern Brazil

Endophytic species of Colletotrichum associated with Mangifera indica (mango) are poorly understood. In this study, Colletotrichum species were isolated from mango in Pernambuco State, Brazil. There were significant differences in isolation frequencies of Colletotrichum species among sites and plant tissues. Mature leaf blades were colonized by most Colletotrichum isolates at the majority of sites. Partial sequences of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of 97 Colletotrichum isolates were amplified as an initial measure of genetic diversity. Phylogenetic analysis with a subset of 22 isolates were performed based on a multi-locus dataset (ACT, TUB2, CAL, CHS-1, GAPDH, ITS) followed by Apn2/MAT IGS sequence-analysis for isolates within the C. gloeosporioides species complex. Molecular analysis associated with phenotypic characteristics revealed six previously described species [C. asianum, C. cliviae, C. dianesei (syn. C. melanocaulon), C. fructicola, C. karstii and C. tropicale] and one new species. This new species is introduced as C. endomangiferae. All species isolated were pathogenic on mango fruits but varied in their virulence. There was no distribution pattern of species among sites and plant tissues, although C. asianum was the most prevalent species at all sites and in all plant tissues studied. Five previously reported Colletotrichum species causing anthracnose in mango fruits in northeastern Brazil were also recovered as endophytes.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.     

Factors Influencing the Use of Sentinel Lymph Node Biopsy in the Netherlands

Background

In the US, whether a sentinel lymph node biopsy (SLNB) is performed depends on tumor and patient factors, including socioeconomic status (SES) and type of health care insurance. We analyzed which patient and tumor characteristics influenced the use of SLNB in a country where every patient has equal access to healthcare.

Methods

Patients diagnosed with a cutaneous invasive melanoma of ≥1 mm between 2004 and 2011 and living in the northeastern part of the Netherlands were selected from the Netherlands Cancer Registry. Regression analysis was performed to assess the association of patient and tumor characteristics and SLNB use.

Results

SLNB was performed in 42 % of the 2,413 included patients. The frequency of performing SLNB increased between 2004 and 2011 from 24 to 55 % (p < 0.001). Patients were less likely to undergo SLNB if they had a melanoma located in the head and neck area (p < 0.001), when they were over 55 years (p = 0.001), and if they had a low SES (p = 0.03). SLNB use was more likely when the diagnosis of melanoma was made in the university hospital (p = 0.045) or when the Breslow thickness was 2.01–4.0 mm (p = 0.03).

Conclusions

The use of SLNB has increased significantly between 2004 and 2011. However, in 2011 it was still performed in only 55 % of the Dutch patients with a melanoma ≥1 mm. In patients with head and neck melanoma, older patients, and patients with low SES, SLNB was less frequently performed. Patients with T3 melanomas and a diagnosis made in the university hospital more often had an SLNB performed.