Endoscopic closure of a gastrocolic fistula using the over-the-scope-clip-system

Gastrointestinal (GI) defects such as fistulas and leaks can be potentially closed endoscopically using hemo-clips and loops. However, hemoclips may not allow for closure of large defects and they do not exert enough tensile force to keep fibrotic defects larger than 5 mm approximated. Herein we present a case of successful endoscopic closure of a gastrocolic fistula in a severely malnourished patient with complex post-surgical upper GI anatomy. We strongly believe that this device is a major breakthrough for the management of various types of discontinuity defects or fistulas. In addition, we show the usefulness of placing a direct jejunostomy using the double balloon enteroscopy (DBE) technique during the same procedure. The concept of providing direct jejunal feedings while allowing for upper gas-trointestinal bowel rest to promote the healing of the minimally invasive endoscopic operation is novel. Thus, our case is unique and exemplifies the utility of mini-mally invasive endoscopic endoluminal surgery.     

The quality of work life of registered nurses in Canada and the United States: a comprehensive literature review

Background: Workplace environment is related to the physical and psychological well-being, and quality of work life (QWL) for nurses.

Objective: The aim of this paper was to perform a comprehensive literature review on nurses’ quality of work life to identify a comprehensive set of QWL predictors for nurses employed in the United States and Canada.

Methods: Using publications from 2004–2014, contributing factors to American and Canadian nurses’ QWL were analyzed. The review was structured using the Work Disability Prevention Framework. Sixty-six articles were selected for analysis.

Results: Literature indicated that changes are required within the workplace and across the health care system to improve nurses' QWL. Areas for improvement to nurses’ quality of work life included treatment of new nursing graduates, opportunities for continuing education, promotion of positive collegial relationships, stress-reduction programs, and increased financial compensation.

Conclusions: This review’s findings support the importance of QWL as an indicator of nurses’ broader work-related experiences. A shift in health care systems across Canada and the United States is warranted where health care delivery and services are improved in conjunction with the health of the nurses working in the system.     

Predictability of Sirius dual-scanning corneal tomography in the measurement of corneal power after photorefractive surgery

Determining an accurate central corneal power (K) measurement is crucial for calculating the intraocular lens power in patients who are undergoing cataract extraction. The ideal method for measuring K is to use a device that works independently of the refractive surgery information. The Scheimpflug camera system offers a promising means of measuring the true corneal power after keratorefractive surgery. In this study, we investigated the accuracy of this system in measuring central corneal power after photorefractive corneal surgery by comparing it to the theoretically derived central corneal power by history method. A total of 120 eyes of 65 (35 females and 30 males) patients were included in this study. The mean change of refraction at the spectacle plane was 3.75 D, whereas the mean change of refraction at the corneal plane was 3.37 D. Using the Sirius dual-scanning corneal tomography, the mean change in corneal power was 3.96 D. No significant differences were detected between the mean post-operative corneal power measured by the Sirius tomographer and the mean change in refraction at the corneal plane calculated clinically (P = 0.076) and the correlation was found to be high (0.913). This study suggests that Sirius dual-scanning corneal tomography offers high predictability when measuring the central 5 mm corneal power in patients who have had myopic corneal photorefractive surgery.     

Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma

Relapsed or refractory non-Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad-spectrum multi-kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub-types of NHL who had received at least one prior therapy. The most common sub-types were diffuse large B-cell lymphoma (24%), follicular lymphoma, grade 1/2 (21%) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; 21%). Most patients were heavily pre-treated, including 42% with more than four prior therapies, 67% with rituximab exposure and 24% with prior autologous transplant. In this cohort, dasatinib showed modest activity in evaluable patients with an objective response rate of 29% (7/24) and clinical benefit rate of 71% (17/24). In 32 patients with outcome data, median progression-free survival was 3 months and median overall survival was 22·4 months. There were two patients with sustained complete responses, both with PTCL-NOS histology. The side effect profile was consistent with prior studies, with pleural effusion being the most common non-haematological toxicity. Exploratory genomic analysis showed two cases of PTCL-NOS with sustained response had a common mutation in LRRK2 and high prevalence of FOXO1 mutation in relapsed/refractory follicular lymphoma.     

DLK1 is a novel regulator of bone mass that mediates estrogen deficiency–induced bone loss in mice

Delta‐like 1/fetal antigen 1 (DLK1/FA‐1) is a transmembrane protein belonging to the Notch/Delta family that acts as a membrane‐associated or a soluble protein to regulate regeneration of a number of adult tissues. Here we examined the role of DLK1/FA‐1 in bone biology using osteoblast‐specific Dlk1‐overexpressing mice (Col1‐Dlk1). Col1‐Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). Micro–computed tomographis (µCT) scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue‐level histomorphometric analysis demonstrated decreased bone‐formation rate and enhanced bone resorption in Col1‐Dlk1 mice compared with wild‐type mice. At a cellular level, Dlk1 markedly reduced the total number of bone marrow (BM)–derived colony‐forming units fibroblasts (CFU‐Fs), as well as their osteogenic capacity. In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast‐dependent increased production of proinflammatory bone‐resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)–induced bone loss was associated with increased production of Dlk1 in the bone marrow by activated T cells. Interestingly, Dlk1^?/? mice were significantly protected from ovx‐induced bone loss compared with wild‐type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss. © 2011 American Society for Bone and Mineral Research.     

Mouse Embryonic Fibroblasts (MEF) Exhibit a Similar but not Identical Phenotype to Bone Marrow Stromal Stem Cells (BMSC)

Mouse embryonic fibroblasts have been utilized as a surrogate stem cell model for the postnatal bone marrow-derived stromal stem cells (BMSC) to study mesoderm-type cell differentiation e.g. osteoblasts, adipocytes and chondrocytes. However, no formal characterization of MEF phenotype has been reported. Utilizing standard in vitro and in vivo assays we performed a side-by-side comparison of MEF and BMSC to determine their ability to differentiate into mesoderm-type cells. BMSC were isolated from 8-10?weeks old mouse bone marrow by plastic adherence. MEF were established by trypsin/EDTA digestion from E13.5 embryos after removing heads and viscera, followed by plastic adherence. Compared to BMSC, MEF exhibited telomerase activity and improved cell proliferation as assessed by q-PCR based TRAP assay and cell number quantification, respectively. FACS analysis revealed that MEF exhibited surface markers characteristic of the BMSC: Sca-1(+), CD73(+), CD105(+), CD29(+), CD44(+), CD106(+), CD11b(-), and CD45(-). In contrast to BMSC, ex vivo osteoblast (OB) differentiation of MEF exhibited a less mature osteoblastic phenotype (less alkaline phosphatase, collagen type I and osteocalcin) as assessed by real-time PCR analysis. Compared to BMSC, MEF exhibited a more enhanced differentiation into adipocyte and chondrocyte lineages. Interestingly, both MEF and BMSC formed the same amount of heterotopic bone and bone marrow elements upon in vivo subcutaneous implantation with hydroxyapatite/tricalcium phosphate, in immune deficient mice. In conclusion, MEF contain a population of stem cells that behave in ex vivo and in vivo assays, similar but not identical, to BMSC. Due to their enhanced cell growth, they may represent a good alternative for BMSC in studying molecular mechanisms of stem cell commitment and differentiation to osteoblasts, adipocytes and chondrocytes.     

Hypoalbuminemia in colorectal cancer prognosis:Nutritional marker or inflammatory surrogate?

Albumin is the single most abundant protein in the human serum. Its roles in physiology and pathology are diverse. Serum albumin levels have been classically thought to reflect the nutritional status of patients. This concept has been challenged in the last two decades as multiple factors, such as inflammation, appeared to affect albumin levels independent of nutrition. In general, cancer patients have a high prevalence of hypoalbuminemia. As such, the role of hypoalbuminemia in patients with colorectal cancer has received significant interest. We reviewed the English literature on the prognostic value of pretreatment albumin levels in colorectal cancer. We also consolidated the evidence that led to the current understanding of hypoalbuminemia as an inflammatory marker rather than as a nutritional one among patients with colorectal cancer.