In Vitro Generation of Atrioventricular Heart Valve Neoscaffolds

Tissue engineering of cardiovascular structures represents a novel approach to improve clinical strategies in heart valve disease treatment. The aim of this study was to engineer decellularized atrioventricular heart valve neoscaffolds with an intact ultrastructure and to reseed them with umbilical cord‐derived endothelial cells under physiological conditions in a bioreactor environment. Mitral (n = 38) and tricuspid (n = 36) valves were harvested from 40 hearts of German Landrace swine from a selected abattoir. Decellularization of atrioventricular heart valves was achieved by a detergent‐based cell extraction protocol. Evaluation of the decellularization method was conducted with light microscopy and quantitative analysis of collagen and elastin content. The presence of residual DNA within the decellularized atrioventricular heart valves was determined with spectrophotometric quantification. The described decellularization regime produced full removal of native cells while maintaining the mechanical stability and the quantitative composition of the atrioventricular heart valve neoscaffolds. The surface of the xenogeneic matrix could be successfully reseeded with in vitro‐expanded human umbilical cord‐derived endothelial cells under physiological flow conditions. After complete decellularization with the detergent‐based protocol described here, physiological reseeding of the xenogeneic neoscaffolds resulted in the formation of a confluent layer of human umbilical cord‐derived endothelial cells. These results warrant further research toward the generation of atrioventricular heart valve neoscaffolds on the basis of decellularized xenogeneic tissue.     

Laser therapy and photosensitive medication: a review of the evidence

In the 2009 guidelines from the BMLA, the use of non-essential aesthetic lasers was contraindicated in patients receiving medication that causes whole-body photosensitisation as well as those causing local light sensitisation. Following this and anecdotal advice, many laser centres refuse to treat patients who are on known photosensitive medication. Therefore, specific patient cohorts that would benefit from laser therapy are being denied because of medications, such as long-term antibiotics for chronic facial acne. This article reviews the published literature on lasers and photosensitive medications, the mechanisms of photosensitivity and the role of laser in its production. The aim is to analyse the available evidence regarding adverse reactions to laser treatment related to photosensitive medication. A PubMed review of published article titles and abstracts was performed using the search term Laser with each of the following terms individually: photosensitive, photosensitiser, photosensitizer, phototoxicity, photoallergy, complications, case-report, tetracycline, minocycline, amiodarone, nitrofurantoin and medication. Four publications were identified, none of which reported any complication in the use of laser in patients taking photosensitising medication. As there are no published accounts of adverse effects of laser in patients with photosensitive medication, we performed a review of the mechanism of photosensitivity by compiling a list of photosensitive medication and the peak wavelength of radiation required to activate the drug. We recommend a national database of drugs and the wavelengths causing photosensitive reactions of each which a laser department can access prior to treatment.     

Open reconstruction of recurrent vesicourethral anastomotic stricture after radical prostatectomy

Objectives

To determine the outcomes of open vesicourethral anastomotic reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP).

Methods

Review of all cases of VUAR within an IRB-approved database was performed. Preoperative factors assessed included cancer treatment modality, duration of symptoms, prior treatments, and length of defect. Outcomes reviewed included length-of-stay (LOS), complications, maintenance of patency, continence, and need for additional procedures.

Results

Twelve cases of VUAR performed by a single surgeon (BJF) from 2004 to 2012 were identified. Surgical approaches were either abdominal (7), perineal (3), or abdominoperineal (2). All patients underwent prior RP, with 25 % having subsequent radiotherapy. Among patients with stenosis, 43 % were completely obliterated. Two cases had prior anastomotic disruption in the early postoperative period after RP. The median length of stenosis was 2.5 cm (range 1–5 cm) and median LOS was 3.0 days (range 1–7 days). At a median follow-up of 75.5 months (range 14–120 months), 92 % of men retained patency; only 25 % were continent.

Conclusion

In experienced hands, VUAR can restore durable patency for men afflicted with outlet stenosis after RP. Despite anatomic restoration, incontinence is likely.     

Antagonizing the αvβ3 Integrin Inhibits Angiogenesis and Impairs Woven but Not Lamellar Bone Formation Induced by Mechanical Loading

Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non‐damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid‐diaphysis of the adult rat forelimb. α_vβ₃ integrin–targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β₃ integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF‐loaded limbs was increased compared with non‐loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF‐ and LBF‐loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post‐yield behavior. These results demonstrate that α_vβ₃ integrin–mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research.     

Evaluation of the 3-Dimensional,Weight-Bearing Orientation of the Normal Adult Knee

The purpose of this study was to use 3-dimensional, weight-bearing images corrected for rotation to establish normative data of limb alignment and joint line orientation in asymptomatic, adult knees. One hundred adults (200 lower extremities) were recruited to receive weight-bearing, simultaneous biplanar imaging of both lower extremities. Multiple radiographic parameters were measured from 3D images, corrected for limb rotation. 70.0% of knees were in neutral, 19.5% in varus, and 10.5% in valgus overall alignment. Only 31 % of knees possessed both a neutral mechanical axis and the absence of joint line obliquity. There was substantial agreement between the 2D and 3D images for overall mechanical alignment (κ = 0.77), but only a moderate agreement for joint line obliquity (κ = 0.58). A substantial portion of asymptomatic adults possess either a varus or valgus mechanical alignment and joint line obliquity.     

Supporting older people following out of hours discharge from the Emergency Department: An integrative review of the literature

Background

For many older people the emergency department (ED) is an important but sometimes difficult step in their healthcare journey. They often attend the ED with co and multi morbidities. Discharge home at evenings and weekends when post-discharge support services are limited can result in a delay or failure to follow through on their discharge plan leading to adverse health outcomes and in some cases, readmission to ED.

Objective

The aim of this integrative review was to identify and appraise the support available to older people following discharge from the ED out of hours (OOH).

Methods

For this review, out of hours referred to those times after 17.30 until 08.00 a.m. on Mondays to Fridays, all hours on weekends and public holidays. Whittemore and Knafl's (Journal of Advanced Nursing, 2005;52:546), framework was used to guide all stages of the review process. Articles were retrieved following a rigorous search of published works using various databases, the grey literature and hand search of the reference lists of the studies included.

Results

In total 31 articles were included in the review. These comprised systematic reviews, randomised control studies, cohort studies and surveys. Main themes identified included processes that enable support, support provision by health and social care professionals and telephone follow-up. Results identified a significant dearth of out of hours discharge research and a strong recommendation for more concise and thorough research in this important area of care transition.

Conclusion

Older person discharge home from the ED presents an associated risk as previous research has identified frequent readmission and periods of ill health and dependency. Out of hours discharge can be even more problematic when it may be difficult to arrange support services and ensure continuity of care. Further work in this area is required, taking cognisance of the findings and recommendations identified in this review.     

Open Versus Minimally Invasive Resection of Gastric GIST: A Multi-Institutional Analysis of Short- and Long-Term Outcomes

Background

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Overall surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of GIST are limited to small, single-institution experiences.

Methods

A total of 397 patients who underwent open surgery (n = 230) or MIS (n = 167) for a gastric GIST between 1998 and 2012 were identified from a multicenter database. The impact of MIS approach on recurrence and survival was analyzed using propensity-score matching by comparing clinicopathologic factors between patients who underwent MIS versus open resection.

Results

There were 19 conversions (10 %) to open; the most common reasons for conversion were tumor more extensive than anticipated (26 %) and unclear anatomy (21 %). On multivariate analysis, smaller tumor size and higher body mass index (BMI) were associated with receipt of MIS. In the propensity-matched cohort (n = 248), MIS resection was associated with decreased length of stay (MIS, 3 days vs open, 8 days) and fewer ≥ grade 3 complications (MIS, 3 % vs open, 14 %) compared with open surgery. High rates of R0 resection and low rates of tumor rupture were seen in both groups. After propensity-score matching, there was no difference in recurrence-free or overall survival comparing the MIS and the open group (both p > 0.05).

Conclusions

An MIS approach for gastric GIST was associated with low morbidity and a high rate of R0 resection. The long-term oncological outcome following MIS was excellent, and therefore the MIS approach should be considered the preferred approach for gastric GIST in well-selected patients.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.