Aim
Anastomotic leakage is the most serious complication following low anterior resection for rectal cancer and is a major cause of postoperative morbidity and mortality. The object of the present ...study was to investigate whether rectal tube drainage can reduce anastomotic leakage after minimally invasive rectal cancer surgery.
Method
Three hundred and seventy‐four patients who underwent laparoscopic or robotic LAR for tumours located ≤ 15 cm above the anal verge between 1 April 2012 and 31 October 2014 were assessed retrospectively. Of these, 107 with intermediate risk of anastomotic leakage received transanal rectal tube drainage. The rectal tube group was matched by propensity score analysis with patients not having rectal tube drainage, giving 204 patients in the study. Covariates for propensity score analysis included age, sex, body mass index, tumour height from the anal verge and preoperative chemoradiation.
Results
Patient demographics, tumour location, preoperative chemoradiation and operative results were similar between the two groups. The overall leakage rate was 10.8% (22/204), with no significant difference between the rectal tube group (9.8%) and the nonrectal tube group (11.8%, P = 0.652). Of the patients with anastomotic leakage, major leakage requiring reoperation developed in 11.8% of those without and 3.9% of those with a rectal tube. On multivariate analysis, age over 65 years and nonuse of a rectal tube were found to be independent risk factors for major anastomotic leakage.
Conclusion
Rectal tube placement may be a safe and effective method of reducing the rate of major anastomotic leakage, alleviating the clinical course of leakage following minimally invasive rectal cancer surgery.
Background and Objective
Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti‐inflammatory activities. However, the ...effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease.
Material and Methods
LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol–water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)‐1β and IL‐6. We used real‐time polymerase chain reaction to quantify inducible NO synthase, IL‐1β, IL‐6, heme oxygenase (HO)‐1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO‐1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA‐binding activities of NF‐κB subunits were analyzed by using the enzyme‐linked immunosorbent assay‐based kits.
Results
CAPE exerted significant inhibitory effects on P. intermedia LPS‐induced production of NO, IL‐1β and IL‐6 as well as their mRNA expression in RAW264.7 cells. CAPE‐induced HO‐1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO‐1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS‐induced NO production. CAPE did not interfere with IκB‐α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF‐κB p65 and p50 subunits induced with LPS, and lessened LPS‐induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS‐induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS‐stimulated cells.
Conclusion
Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease. In vivo studies are required to appraise the potential of CAPE further as an immunomodulator in the treatment of periodontal disease.
Although a large amount of acoustic indicators have already been proposed in the literature to evaluate the hypokinetic dysarthria of people with Parkinson's Disease, the goal of this work is to ...identify and interpret new reliable and complementary articulatory biomarkers that could be applied to predict/evaluate Parkinson's Disease from a diadochokinetic test, contributing to the possibility of a further multidimensional analysis of the speech of parkinsonian patients. The new biomarkers proposed are based on the kinetic behaviour of the envelope trace, which is directly linked with the articulatory dysfunctions introduced by the disease since the early stages. The interest of these new articulatory indicators stands on their easiness of identification and interpretation, and their potential to be translated into computer based automatic methods to screen the disease from the speech. Throughout this paper, the accuracy provided by these acoustic kinetic biomarkers is compared with the one obtained with a baseline system based on speaker identification techniques. Results show accuracies around 85% that are in line with those obtained with the complex state of the art speaker recognition techniques, but with an easier physical interpretation, which open the possibility to be transferred to a clinical setting.
Background and Objective
Daidzein is an isoflavone abundant in soybeans, kudzu root and red clover, which have been widely studied for its therapeutic potential. The present study was designed to ...evaluate the effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis by assessing morphological data obtained from micro‐computed tomography (micro‐CT).
Material and Methods
Twenty‐four male Sprague‐Dawley rats were randomly assigned to the following three groups comprising eight animals each: the nonligation (NL) group; the ligation (L) group; and the ligation+daidzein (LD) group. To induce periodontitis, a 4‐0 braided silk ligature was tied around the cervical area of the lower‐right first molars of rats in groups L and LD. Rats in the LD group were given daily doses of daidzein (10 mg/kg of body weight) by intraperitoneal injection immediately after ligature placement. Two weeks after the placement of ligatures, mandibular block biopsies were scanned using a micro‐CT system.
Results
Daily administration of daidzein strongly suppressed the ligature‐induced loss of alveolar bone height. In addition, when rats were treated with daidzein, the ligature‐induced decrease in the bone volume fraction was significantly recovered. Furthermore, daidzein significantly reversed ligature‐induced deteriorations in the microarchitecture parameters of trabecular bone, such as trabecular thickness, bone mineral density, trabecular separation and structure model index.
Conclusion
The study presented here demonstrates, for the first time, that daidzein effectively reduces alveolar bone destruction resulting from experimental periodontitis in rats. Further studies are necessary for the translation of this compound clinically to improve the outcomes of patients diagnosed with periodontitis.
To identify microbial squalene that has been widely used in various industrial applications, intracellular formation of photosynthetic squalene was investigated using the previously engineered ...Synechococcus elongatusPCC 7942 strain. Unlike the proposed localization of squalene in the membrane bilayer, small droplets were identified in the cytoplasm of S. elongatusPCC 7942 as squalene using transmission electron microscopy analysis. Determination of the diameters of the squalene droplets with manual examination of 1016 droplets in different squalene‐producing strains indicated larger squalene droplets in larger cells. Based on the observation of a sole droplet of squalene in a cyanobacterium, fluorescent Nile red was used for the selective staining of squalene. The fluorescent intensities were correlated with squalene contents determined using gas chromatography‐mass spectrometry. Photosynthetic squalene was identified as a small droplet in S. elongatusPCC 7942, and this noninvasive quantitative method could be useful to promote high‐throughput strain development for squalene production.
Significance and Impact of the Study
Engineering of Cyanobacteria has focused on sustainable production of squalene by converting CO2. Before improving the photosynthetic squalene production, we characterized formation of squalene, showing small droplets in the cytoplasm instead of single granule. Based on the finding and the analysis, this study has provided valuable evidences how further metabolic engineering strategies should apply to enhance the production yield.
Significance and Impact of the Study: Engineering of Cyanobacteria has focused on sustainable production of squalene by converting CO2. Before improving the photosynthetic squalene production, we characterized formation of squalene, showing small droplets in the cytoplasm instead of single granule. Based on the finding and the analysis, this study has provided valuable evidences how further metabolic engineering strategies should apply to enhance the production yield.
A large‐eddy simulation is used to investigate contaminant transport owing to complex human and door motions and vent‐system activity in room compartments where a contaminated and clean room are ...connected by a vestibule. Human and door motions are simulated with an immersed boundary procedure. We demonstrate the details of contaminant transport owing to human‐ and door‐motion‐induced wake development during a short‐duration event involving the movement of a person (or persons) from a contaminated room, through a vestibule, into a clean room. Parametric studies that capture the effects of human walking pattern, door operation, over‐pressure level, and vestibule size are systematically conducted. A faster walking speed results in less mass transport from the contaminated room into the clean room. The net effect of increasing the volume of the vestibule is to reduce the contaminant transport. The results show that swinging‐door motion is the dominant transport mechanism and that human‐induced wake motion enhances compartment‐to‐compartment transport.
Practical Implications
The effect of human activity on contaminant transport may be important in design and operation of clean or isolation rooms in chemical or pharmaceutical industries and intensive care units for airborne infectious disease control in a hospital. The present simulations demonstrate details of contaminant transport in such indoor environments during human motion events and show that simulation‐based sensitivity analysis can be utilized for the diagnosis of contaminant infiltration and for better environmental protection.
Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant ...chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.
The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).
A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.
In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
•In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy.•The addition of radiotherapy to chemotherapy did not significantly reduce the rate of recurrence after D2 gastrectomy.•DFS between patients treated with adjuvant chemotherapy and chemoradiotherapy was similar across all subgroups, including Lauren classification.
Salivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low ...postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance.
We verified the relationship between AMY1 CNVs and homeostatic model assessment-insulin resistance (HOMA-IR) in a cohort of 1257 Korean men aged 20-65 years who visited two medical centres for regular health check-ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≥ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded.
AMY1 CNVs correlated negatively with HOMA-IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMA-IR were more evident among non-smokers and regular drinkers and were non-significant among smokers and non-regular drinkers.
Low AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption.
Summary Background The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned ...interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. Methods CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II–IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m2 twice daily on days 1–14 plus intravenous oxaliplatin 130 mg/m2 on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov , NCT00411229. Findings We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54–70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio HR 0·58, 95% CI 0·47–0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63–73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47–58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51–0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74–82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64–73) in the observation group. Adverse event data were not collected after the primary analysis. Interpretation Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. Funding F Hoffmann La-Roche and Sanofi.
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