Background
Patterns of recurrence after surgery with postoperative chemoradiotherapy (S‐CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might ...influence the nature and timing of subsequent management strategies.
Methods
Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan–Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease‐free survival.
Results
A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S‐CCRT. Propensity score matching yielded 213 well balanced pairs. The 3‐year overall survival rate and median survival time in the S‐CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery‐alone group (P = 0·006). The 3‐year disease‐free survival rate and median disease‐free survival time in the S‐CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery‐alone group (P = 0·006). The 2‐year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S‐CCRT and surgery‐alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease‐free survival included age over 56 years, pT3–4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001).
Conclusion
Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.
Longer survival and less recurrence with multimodal treatment
To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic ...Gen-Probe Prodesse assays—on the detection of viral respiratory infections.
A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay.
Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848–0.949), 0.949 (95% confidence interval, 0.882–0.979) and 0.954 (95% confidence interval, 0.871–0.985), respectively. The three mPCRs were comparable in terms of detection of FluA.
Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.
To identify microRNAs (miRNAs) that may have a causal role in hepatocarcinogenesis, we used an animal model in which C57BL/6 mice fed choline-deficient and amino acid defined (CDAA) diet develop ...preneoplastic lesions at 65 weeks and hepatocellular carcinomas after 84 weeks. miRNA expression profiling showed significant upregulation of miR-181b and miR-181d in the livers of mice as early as 32 weeks that persisted at preneoplastic stage. The expression of tissue inhibitor of metalloprotease 3 (TIMP3), a tumor suppressor and a validated miR-181 target, was markedly suppressed in the livers of mice fed CDAA diet. Upregulation of hepatic transforming growth factor (TGF)b and its downstream mediators Smad 2, 3 and 4 and increase in phospho-Smad2 in the liver nuclear extract correlated with elevated miR-181b/d in mice fed CDAA diet. The levels of the precursor and mature miR-181b were augmented on exposure of hepatic cells to TGFβ and were significantly reduced by small interference RNA-mediated depletion of Smad4, showing the involvement of TGFβ signaling pathway in miR-181b expression. Ectopic expression and depletion of miR-181b showed that miR-181b enhanced matrix metallopeptidases (MMP)2 and MMP9 activity and promoted growth, clonogenic survival, migration and invasion of hepatocellular carcinoma (HCC) cells that could be reversed by modulating TIMP3 level. Further, depletion of miR-181b inhibited tumor growth of HCC cells in nude mice. miR181b also enhanced resistance of HCC cells to the anticancer drug doxorubicin. On the basis of these results, we conclude that upregulation of miR-181b at early stages of feeding CDAA diet promotes hepatocarcinogenesis. Oncogene (2010) 29, 1787-1797; doi: 10.1038/onc.2009.468; published online 21 December 2009 Keywords: miR-181b; TIMP3; hepatocarcinogenesis; CDAA diet; doxorubicin; hepatocullular carcinoma
Traffic emissions are a significant source of airborne particulate matter (PM) in ambient environments. These emissions contain an abundance of toxic metals and thus pose adverse effects on human ...health. Size-fractionated aerosol samples were collected from May to September 2013 by using micro-orifice uniform deposited impactors (MOUDIs). Sample collection was conducted simultaneously at the inlet and outlet sites of Hsuehshan Tunnel in northern Taiwan, which is the second-longest freeway tunnel (12.9 km) in Asia. This endeavor aims to characterize the chemical constituents and size distributions, as well as fingerprinting ratios of particulate metals emitted by vehicle fleets. A total of 36 metals in size-resolved aerosols were determined through inductively coupled plasma mass spectrometry. Three major groups – namely, tailpipe emissions (Zn, Pb, and V in fine mode), wear debris (Cu, Cd, Fe, Ga, Mn, Mo, Sb, and Sn), and resuspended dust (Ca, Mg, K, and Rb) – of airborne PM metals were categorized on the basis of the results of enrichment factor, correlation matrix, and principal component analysis. Size distributions of wear-originated metals resembled the pattern of crustal elements, which were predominated by super-micron particulates (PM1–10). By contrast, tailpipe exhaust elements such as Zn, Pb, and V were distributed mainly in submicron particles. By employing Cu as a tracer of wear abrasion, several inter-metal ratios – including Fe / Cu (14), Ba / Cu (1.05), Sb / Cu (0.16), Sn / Cu (0.10), and Ga / Cu (0.03) – served as fingerprints for wear debris. However, the data set collected in this work is useful for further studies on traffic emission inventory and human health effects of traffic-related PM.
Body mass index (BMI) and mortality in old adults from the general population have been related in a U‐shaped or J‐shaped curve. However, limited information is available for elderly nursing home ...populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m²), the most adjusted hazard ratios (HRs) according to a pre‐defined list of covariates were obtained from authors and pooled by random‐effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow‐up were meta‐analysed. Compared with normal weight, all‐cause mortality HRs were 1.41 (95% CI = 1.26–1.58) for underweight, 0.85 (95% CI = 0.73–0.99) for overweight and 0.74 (95% CI = 0.57–0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 95% CI = 1.13–2.40). RR results corroborated primary HR results, with additionally lower infection‐related mortality in overweight and obese than in normal‐weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
To determine the effectiveness of social media-based interventions in promoting positive changes in nutrition behaviors amongst adolescents, and identify the behavior change technique(s) (BCT(s)) ...that were used in effective interventions.
MEDLINE, Embase, PsycINFO, Cinahl, and Cochrane library were systematically searched. Eligible studies included: participants aged 13–18 years; use of one or more social media platform(s) in the intervention; a comparison group not exposed to the social media-based intervention; nutrition- and diet-related behavior outcome(s); and an experimental study design. BCTs were identified using a behavior change taxonomy. Quality and risk of bias assessments were also conducted.
Seven eligible interventions were included, varying from internet-only programs to in-person programs with internet or website-based component(s). Studies used relatively outdated forms of social media such as purpose-built discussion boards or chat rooms rather than commercial social media interfaces (e.g. Facebook). Five of the seven interventions demonstrated improvements in at least one nutrition behavior. The most common improvement was for fruit or vegetable intake, and two of four studies showed improvements for sugar-sweetened beverage consumption. The most common BCT used was social support, followed by demonstration of behavior, self-monitoring, goal setting, and feedback.
The current evidence base is equivocal with respect to changing overall dietary behaviors, as increasing intakes of desirable food groups were more successful than decreasing unfavorable food habits. Further research using better quality interventions, full description of the BCTs, long-term follow-up, and popular contemporary social media platforms to build the evidence base are required.
Transforming growth factor-α (TGF-α)-induced proliferation and transforming growth factor-β (TGF-β)-mediated quiescence are intricately balanced in normal lung-tissue homeostasis but are deregulated ...during neoplastic progression of lung cancer. Here, we show that Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a novel MYC-interacting transcriptional modulator, responds to TGF-α induction and TGF-β suppression to orchestrate cellular proliferation and quiescence, respectively. Upon TGF-α induction, CITED2 was induced by MYC and further modulated MYC-mediated transcription in a feed-forward manner. CITED2 recruited p300 to promote MYC-p300-mediated transactivation of E2F3, leading to increased G1/S cell cycle progression. Moreover, CITED2 inhibited cellular quiescence by enhancing MYC-mediated suppression of p21(CIP1). CITED2 interacted with histone deacetylase 1 (HDAC1) and potentiated MYC-HDAC1 complex formation. TGF-β stimulation provoked downregulation of CITED2, which abrogated MYC-HDAC1-mediated p21(CIP1) suppression, causing cellular quiescence. Ectopic CITED2 expression enhanced tumor growth in nude mice; furthermore, CITED2 knockdown caused tumor shrinkage and increased overall host mouse survival rates. Expression of CITED2/MYC/E2F3/p21(CIP1) signaling molecules was associated with poor prognosis of lung cancer patients. Thus, CITED2 functions as a molecular switch of TGF-α and TGF-β-induced growth control, and MYC-CITED2 signaling axis provides a new index for predicting clinical outcome.
Background: Morphine consumption after a given surgical procedure can vary considerably. Studies show that single nucleotide polymorphism involving the nucleotide position 118 at exon 1 of the ...μ‐opioid receptor gene (OPRM1) may play a role in mediating the effects of opioids. This study was performed to correlate the A118G polymorphism at OPRM1 with morphine consumption in patients undergoing total knee arthroplasty.
Methods: Post‐operative pain was relieved by patient‐controlled analgesia (PCA). The analgesic effect was evaluated using a visual analogue scale. Side‐effects, such as sedation, nausea and vomiting, and pruritus, were recorded systematically. The genotypes were determined by sequencing polymerase chain reaction‐amplified DNA. The differences in demographics and consumed morphine from the PCA device between the different genotypes were tested using one‐way analysis of variance. The prevalence of side‐effects from morphine and sex distribution were compared using the Kruskal–Wallis test.
Results: One hundred and forty‐seven patients were included in the study. Twenty‐seven patients who required rescue analgesia were excluded; these patients did not differ demographically or genetically from the 120 who completed the study. Of the latter, 74 were A118 homozygous (AA), 33 were heterozygous (AG) and 13 were G118 homozygous (GG). Group GG consumed significantly more morphine (40.4 ± 22.0 mg) than group AA (25.3 ± 15.5 mg) and group AG (25.6 ± 11.7 mg) during the first 48 h post‐operatively. The groups did not differ with respect to reported pain, age, sex, weight and adverse effects.
Conclusions: G118 homozygotes have a poorer response to morphine for post‐operative pain control than A118 homozygotes or heterozygotes. The genotype may thus influence the post‐operative response to pain and cause differences in the amounts of analgesic consumed by patients after total knee arthroplasty.
A short time to positivity (TTP) correlates with poor clinical outcome in patients with Staphylococcus aureus bacteraemia, but the association between sequential TTPs and the outcome of these ...patients is unclear. Sequential TTPs from patients with S. aureus bacteraemia persisting for >48 h were analysed with respect to clinical parameters and patient outcome at a tertiary hospital. During the 5-year study period, 87 patients (9.2%; mean age of 64 years) had persistent S. aureus bacteraemia, with an average Pittsburgh bacteraemia score of 2.7. Forty-eight patients (55%) had methicillin-resistant S. aureus infection, and 28 (32%) had nosocomial infection. The most common underlying disease was end-stage renal disease (43%). The most common type of infection was catheter-related infection (31%), followed by infective endocarditis (18%). The in-hospital mortality rate was 40%. Higher Pittsburgh scores (p 0.005; OR 1.37; 95% CI 1.1–1.7) and a second TTP/first TTP ratio of <1.5 (p 0.004; OR 0.2; 95% CI 0.07–0.6) were independent risk factors for mortality. Among patients receiving adequate empirical therapy, a second positive blood culture growing within 12 h was more frequent in patients who finally died. Factors associated with a second TTP/first TTP ratio of <1.5 included older age (p 0.02; OR 0.96; 95% CI 0.92–0.99) and inadequate empirical antimicrobial therapy (p 0.01; OR 3.53; 95% CI 1.42–8.78). Among patients with persistent S. aureus bacteraemia, a second TTP/first TTP ratio of <1.5 is a predictor of poor outcome. Physicians should search for interventions guaranteeing that all patients with S. aureus bacteraemia receive adequate empirical therapy.
Three-dimensional bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and ...organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photosensitive moiety for UV-induced cross-linking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermosensitive moiety. The photo/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermosensitive properties, these UV-cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5–2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37 °C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermoresponsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (<1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo/thermoresponsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues.
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