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To characterize the longitudinal course of the systemic inflammatory response (SIR) throughout the perioperative period. To investigate whether postoperative changes in the neutrophil-to-lymphocyte ratio (NLR) or lymphocyte-to-monocyte ratio (LMR) when compared with preoperative levels ('conversion') are associated with survival differences in colorectal cancer patients undergoing resection.Recent evidence suggests that preoperative measurements of markers of the SIR including the NLR and LMR are prognostic. However, a few data exist evaluating longitudinal changes in the SIR especially in regards to their association with surgical interventions, optimal timing of assessment, and their effect on patient survival.Data from 6 hospitals from January 1998 to December 2012 were retrospectively collected. We examined 2280 patients with complete data. For the subgroup analysis investigating conversion, we examined 587 patients with full preoperative and postoperative data from 21 to 56 days postoperative. Patients were stratified into 4 groups for analysis of conversion in a multivariate Cox-regression model.A longitudinal profile for the perioperative NLR and LMR was clearly characterized identifying an optimal period of remeasurement at 21 to 56 days postoperation. In multivariate analysis both NLR change group (P0.001) and LMR change group (P0.001) were independently associated with overall survival. For both biomarkers, patients with both a low preoperative and postoperative inflammatory state had the best survival. A change from the preoperative to postoperative inflammatory state was associated with a survival difference.This study characterizes the perioperative SIR profile and provides evidence for the remeasurement of SIR biomarkers postoperatively at 21 to 56 days for further prognostication.

A 3 year and 8 months old Chinese boy was referred for a consultation regarding his missing maxillary anterior teeth. He had a history of trauma to his primary maxillary anterior teeth due to a fall at the age of 16 months. Clinical examination of the patient indicated multiple carious lesions and inadequate oral hygiene. Radiographic examination revealed intrusion of the primary left lateral incisor, with evidence of damage to the permanent tooth germ. Subsequently, the patient was followed-up for almost six years during which his permanent maxillary left lateral incisor erupted exhibiting an unusual morphology. Clinically enamel hypoplasia and radiographically dens invaginatus were evident in affected tooth.

A novel inhalable rifapentine dry powder formulation could improve pulmonary rifapentine concentrations resulting in a significantly shorter time to treat tuberculosis infection. The pharmacokinetics of rifapentine (20mg/kg) in healthy mice was compared following intratracheal (IT) and intraperitoneal (IP) administration. Plasma, bronchoalveolar lavage (BAL) and tissue samples were collected and drug levels were quantified at time points up to 24h. Concentration-time data were analysed using a mixed-effects modelling approach to provide model-based estimates of area under the concentration-time curve from time 0 to infinity (AUC0-∞). IT delivery had considerably higher peak rifapentine lung and BAL concentrations and associated AUC0-∞ compared with IP delivery. The plasma AUC0-∞ following IT dry powder delivery was ca. four-fold smaller than the value for IP delivery. Inhaled delivery of rifapentine has the potential to selectively enhance therapeutic efficacy at the pulmonary site of infection whilst minimising systemic exposure and related toxicity.

Recent murine studies found that rifapentine, dosed daily, at least halved tuberculosis treatment times compared with standard rifampicin and isoniazid-containing regimens. However, in humans, an inhalable form of rifapentine may be necessary to considerably shorten treatment duration because of the physiological barriers associated with oral therapy. The current study compares two inhalable rifapentine dry powders-a novel pure crystalline form and an amorphous form-by a series of in vitro tests. The crystalline and amorphous powders had a mass median aerodynamic size of 1.68 ± 0.03 and 1.92 ± 0.01 μm, respectively, associated with a fine particle fraction of 83.2 ± 1.2% and 68.8 ± 2.1%, respectively. A quinone degradation product was identified in the amorphous powder stored for 1 month, whereas the crystalline form remained chemically stable after storage at both 0% and 60% relative humidity, 25°C, for at least 3 months. Solubilized rifapentine was well tolerated by pulmonary tissue and macrophage cells up to approximately 50 μM. The accumulation of rifapentine within alveolar macrophage cells was significantly higher than for rifampicin, indicating enhanced delivery to infected macrophages. The novel inhalable crystalline form of rifapentine is suitable for targeted treatment of tuberculosis infection and may radically shorten treatment duration.

BackgroundRecent literature has suggested that tumor sidedness in colorectal cancer (CRC) is an independent prognostic and potentially predictive marker of survival. The aims of the study were to determine the prognostic significance of tumor sidedness in colorectal cancer patients undergoing primary tumor resection and to assess associated tumor biology.MethodsA total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012 were analyzed for association with tumor biologic factors and with overall survival. Metastatic patients were excluded from analysis.ResultsLeft sided CRCs were associated with a number of additional key prognostic markers including BRAFV600E wildtype status (PConclusionsTumor sidedness was not an independent prognostic marker of CRC. However, right sided CRCs were associated with several key independent prognostic markers supporting a hypothesis that tumor sidedness is a surrogate for other biomarkers.

Immunohistochemistry has recently been validated for the detection of the BRAFV600E mutation across a range of tumor types. In colorectal carcinoma, the presence of the BRAFV600E mutation can be used to virtually exclude Lynch syndrome in mismatch repair-deficient tumors. In mismatch repair-proficient tumors, BRAFV600E mutation assessed by molecular methods has been proposed as a poor prognostic factor. We investigated whether combined BRAFV600E and mismatch repair status assessment by immunohistochemistry alone can be used as a prognostic marker in the routine clinical setting. We performed immunohistochemistry for BRAFV600E, MLH1, PMS2, MSH2, and MSH6 on 1426 consecutive unselected colorectal carcinomas. Ninety-one (6.4%) carcinomas were mismatch repair-proficient and BRAFV600E mutant, and these tumors demonstrated a significantly worse 5-year survival of 49.7% compared with mismatch repair-proficient BRAF wild type (74.1% of tumors, 65.4% survival), mismatch repair-deficient BRAFV600E mutant (12.9% of tumors, 70.1% survival), and mismatch repair-deficient BRAF wild type (6.6% of tumors, 73.6% survival). The poor survival was confirmed by univariate analysis (P

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of the use of anti‐angiogenic agents (VEGF inhibitors) in the adjuvant setting after resection in patients diagnosed with resectable colorectal cancer. This would permit a summary of the safety and effectiveness of anti‐VEGF therapies overall, as well as in pre‐planned prognostic subgroups, and identify areas where further research could be directed.

6571Background: Recent evidence suggests that markers of systemic inflammation such as the pre-operative Neutrophil-to-lymphocyte ratio (NLR) and the Lymphocyte-to-monocyte ratio (LMR) are accurate...

MYC over-expression as determined by molecular means has been reported as a favorable prognostic biomarker in colorectal carcinoma (CRC). However MYC expression analysis is not available in the routine clinical setting. We investigated whether immunohistochemistry (IHC) for the myc protein using a novel commercially available rabbit monoclonal antibody [clone Y69] which is currently in widespread clinical use for lymphoma diagnosis could be used to predict outcome in resected CRC. Myc IHC was performed on a tissue microarray (TMA) comprising a retrospective cohort of 1421 CRC patients and scored blinded as to all clinical and pathological data. IHC was also performed on a subcohort of whole section CRCs to assess staining characteristics and concordance with TMA expression. MYC over-expression was found in 980 (69%) of CRCs and was associated with tumor stage and DNA mismatch repair/BRAF status. There was substantial agreement between TMA and whole section myc IHC (kappa = 0.742, p

Fifty-four cases of ectopically erupted maxillary permanent first molars were studied with a method using the measurements obtained from photographs of the study casts. The amount of relative loss of anteroposterior arch length of the right and left sides was shown to correlate with the increased mesial angulation of the maxillary permanent first molar. The bilateral ectopic group has a significantly larger mesial angulation of the permanent first molar on a maxilla with shorter anteroposterior arch length. The relative loss of arch length with ectopic eruption of the permanent first molar limits the use of unilateral appliances for treatment. The use of an appliance with bilateral arch support seems preferable.

e14529 Background: Accurate, simple and inexpensive biomarkers will enable better use of cancer treatments. The neutrophil to lymphocyte ratio (NLR) is prognostic in advanced colorectal cancer (CRC...