Risk factors for clinical anastomotic leakage after right hemicolectomy

Purpose

Anastomotic leakage (AL) after right hemicolectomy is a devastating complication, and risk factors for AL in this setting are rarely investigated exclusively. Recent reports suggest that anastomotic type may influence the rate of AL in ileocolic anastomoses. We investigated risk factors and short-term outcomes in patients subjected to right hemicolectomy.

Methods

Data from all patients undergoing right hemicolectomy at our institution between 2009 and 2013 were collected in a database. Risk factors for clinical AL, 30-day mortality, hospital and intensive care unit stay were investigated. Stepwise logistic regression was used to adjust for confounding.

Results

22/445 (4.9 %) patients had AL. Median time to AL was 6 days (range 2–11 days). A stapled anastomosis was associated with an increased AL rate compared with the handsewn approach (adjusted odds ratio (aOR) 2.84; 95 % CI 1.14–7.07; P?=?0.025). Other risk factors for AL were tobacco use (aOR 2.70; 95 % CI 1.06–6.86; P?=?0.037) and diabetes (aOR 5.95; 95 % CI 2.23–15.90; P?<?0.001). Anastomotic ischemia was present in 6/13 stapled and 1/9 handsewn leaking anastomoses, P?=?0.081, while generalized peritonitis was observed after 4/13 stapled and 7/9 handsewn leaking anastomoses, P?=?0.030. Thirty-day mortality was 2/22 (9.1 %) in patients with AL and 23/423 (5.4 %) in patients without AL, P?=?0.468, and 13/160 (8.1 %) and 12/285 (4.2 %), P?=?0.085, in stapled and handsewn anastomoses, respectively.

Conclusions

Risk factors for AL after right hemicolectomy were diabetes, tobacco use and stapled compared with handsewn anastomoses.

     

Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner.     

Single-stage tracheal and cricotracheal segmental resection with end-to-end anastomosis: Outcome,complications, and risk factors

Objective

Management of tracheal stenosis remains controversial. Endoscopic interventions commonly provide immediate relief of symptoms, but are associated with high recurrence rates. In contrast, high success rates have been reported in patients undergoing tracheal resection. However, well-defined indications and contraindications for tracheal resection are lacking and previous studies commonly ignore patient-related outcomes (e.g. dyspnoea). We aimed to evaluate the outcome of tracheal resection at our institution and identify risk factors for complications.

DNA immunization with 2C FMDV non-structural protein reveals the presence of an immunodominant CD8+, CTL epitope for Balb/c mice

Outbreaks of foot and mouth disease virus (FMDV) have devastating economic consequences in affected areas. The presence of multiple serotypes and virus variants makes vaccination complicated. A better understanding of protective immune mechanisms may help in development of novel vaccines with cross protective capacity. While much attention has been devoted to humoral responses to FMDV, less is known about the role of cell-mediated responses in protective immunity. Predictions of potential CTL epitopes by two different computer algorithms identified the viral 2C protein as containing a potential murine H2-Kd CTL epitope located in its amino-terminal half. DNA vaccination of mice with a plasmid expressing the 2C protein and a fragment thereof confirmed that this was indeed a CTL epitope, as shown by interferon gamma (IFN-gamma) induction in CD8+, CD44(hi) splenocytes after in vitro stimulation with peptides containing the amino acid sequence KYKDAKEWL, predicted for the CTL epitope. A peptide with the variant sequence KYKEAKEWL induced similar responses, indicating tolerability towards a conservative substitution at the altered residue. Virus infection likewise induced a measurable CTL response against KYKDAKEWL, although less clear due to a higher background of IFN-gamma production in splenocytes from infected mice. Challenge of vaccinated mice showed that the CTL response induced by the 2C protein was not protective, since viremia and mortality were unaffected by vaccination. The implications for vaccine development are discussed in the context of cross-serotype reactive responses.     

Doing mini-health technology assessments in hospitals: a new concept of decision support in health care?

OBJECTIVES: The purpose of this project was to evaluate local decision support tools used in the Danish hospital sector from a theoretical and an empirical point of view. METHODS: The use of local decision support was evaluated through questionnaires sent to all county health directors, all hospital managers, and all heads of clinical departments in cardiology, orthopedic surgery, and intensive care. In addition, respondents were asked to submit whatever decision support tools they were using (including mini-HTAs, other forms or checklists, and special procedures for decision making concerning new health technologies). A theoretical analysis of the decision support tools (decision theory) was performed as well as a comparison with the business case method used in private companies. Finally, the Danish mini-HTA was compared with foreign production and use of HTA and HTA-like assessments as local decision support. RESULTS: The response rate was high (87 percent, 94 percent, 85 percent, respectively). We collected sixty different forms (of which forty-nine were mini-HTAs) and twenty variants of written procedures. We found theoretical and empirical evidence that local involvement in the process of making the HTA could be important for the use of the results from the HTA and for the process of implementing the new technology. CONCLUSIONS: Doing mini-HTA in hospitals seems to balance the need for quality and depth with the limited time and resources for assessment.     

Inflammatory pathway analysis using a high content screening platform

High content cellular screening assays are useful tools to investigate the interplay between signaling pathways and offer valuable platforms to determine the mode of action, potency, and selectivity of potential drug candidates in a biological setting. We describe a cell-based multiplex fluorescent imaging assay that permits concurrent detection and quantification of the distribution of nuclear factor kappaB (NFkappaB) p65/RelA and phosphorylated forms of p38 and c-Jun between the cytosol and nucleus. Cellular screening, data acquisition, and data interpretation were conducted on the ArrayScan HCS Reader (Cellomics Inc., Pittsburgh, PA). A significant window between untreated and interleukin-1alpha (IL-1alpha) stimulated HeLa cells for all three targets was achieved with low variability. Staining specificity was confirmed with blocking peptides and pharmacological inhibition of p38, c-Jun-N-terminal kinase (JNK), and inhibitory kappaB kinase 2, and channel bleed-through was eliminated or counterbalanced by the use of fixed exposure times together with careful reporter channel selection. The JNK inhibitor SP600125 was used as a demonstration compound because in addition to inhibiting nuclear accumulation of phosphorylated c-Jun it reduced nuclear translocation of phosphorylated p38 and NFkappaB p65/RelA in a dose-dependent manner, indicating a lack of SP600125 selectivity. This was supported by RNA interference where co-transfection of small interfering RNA targeting both JNK1 and JNK2, to limit signaling redundancy, significantly inhibited IL-1alpha-stimulated translocation of phosphorylated c-Jun without altering phosphorylated p38 and NFkappaB p65/RelA redistribution. This image analysis application is a valuable and information-rich screening tool to investigate compound selectivity and/or cross-talk between key signaling pathways involved in the inflammatory response.