Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
Summary Background Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of ...AKI and assess the availability of diagnosis and treatment in China. Methods We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. Findings Of 2 223 230 patients admitted to the 44 hospitals screened in 2013, 154 950 (7·0%) were suspected of having AKI by electronic screening, of whom 26 086 patients (from 374 286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374 286) by KDIGO criteria and 2·03% (7604 of 374 286) by expanded criteria, from which we estimate that 1·4–2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality Interpretation AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. Funding National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.
Objectives This study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms. Background ...Inflammatory processes play a major role in myocardial I/R injury. We recently identified IL-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown. Methods The involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetic deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro. Results Interleukin-17A was elevated after murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes but not CD4+ helper T cells were a major source of IL-17A. Anti–IL-17A monoclonal antibody treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels, and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. In contrast, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule-1 expression. Conclusions IL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration.
To discern the effectiveness and toxicity of stereotactic ablative radiation therapy (SABR) in the elderly population (aged ≥75 years) and to consider how SABR outcomes compare with surgical outcomes ...historically reported in the elderly.
A total of 772 patients with clinical early-stage I-II non-small cell lung cancer (NSCLC; stage T1-T3N0M0) underwent SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) from 2004 to 2014 at our center (n=442, aged <75 years; n=330, aged ≥75 years). The primary endpoints included overall survival (OS), time-to-progression, and grade ≥3 toxicity. The median follow-up time was approximately 55 months.
Compared with patients aged <75 years, those aged ≥75 years had no difference in the time-to-progression (P=.419), lung cancer-specific survival (P=.275), or toxicity (P=.536). OS was the same between both age groups at 2 years of follow-up but diverged thereafter, with patients aged <75 years when treatment began having greater OS rates at 5 years. The median OS rates for patients aged ≥75 years were 86% at 1 year, 57.5% at 3 years, and 39.5% at 5 years. The median OS rates for patients aged <75 years were 87.3% at 1 year, 67.6% at 3 years, and 51.5% at 5 years. No patient aged ≥75 years experienced any grade 4 or 5 toxicity.
The effectiveness of SABR was the same for the elderly as for the average-age population according to lung cancer-specific survival and time-to-progression. It also poses no increased toxicity. Compared with the historical outcomes with surgery in the elderly, SABR outcomes can be considered comparable for stage I-II disease but with less morbidity.
Abstract Background Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on ...risk factors and outcomes of LT for ACLF. Methods The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. Results One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. Conclusions Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.
Abstract Background Late gadolinium enhancement (LGE) is a standard method to evaluate myocardial fibrosis, but restricted due to contrast agent contraindications. Non-contrast T1rho can generate ...endogenous contrast, and detect fibrosis in chronic myocardial infarction. However, T1rho for hypertrophic cardiomyopathy (HCM) patients is still unreported. The present study aimed to investigate T1rho for fibrotic assessment and the clinical implication in HCM patients. Methods 18 HCM patients and 8 controls underwent T1rho, cine, and LGE cardiac magnetic resonance (CMR). T1rho relaxation time maps were created. Left ventricular (LV) parameters assessed included wall thickness, wall thickening, chamber volumes, ejection function, and fibrotic size. New York Heart Association (NYHA) functional classification was conducted. Results Hyper-T1rho value was identified in 12 HCM patients, consistent with LGE. The mean T1rho values of controls, LGE-negative patients, and remote myocardium of LGE-positive patients were 42.2 ± 1.6 ms, 43.9 ± 2.5 ms, and 42.5 ± 1.2 ms respectively, and these values showed no significant difference (all p > 0.05). T1rho-3-SD and T1rho-4-SD fibrotic sizes (32.5 ± 14.0% and 25.1 ± 11.5%) did not differ from LGE fibrotic size (28.1 ± 11.2%) (both p > 0.05). For the fibrotic size, T1rho-3-SD method obtained the strongest correlation with LGE ( r = 0.88, p < 0.001), and T1rho-4-SD obtained the minimal mean difference with LGE (−3.1%; −15.2 to 9.1%), compared with other SDs. All the fibrotic sizes assessed by both methods correlated directly with LV maximal end-diastolic thickness (all p < 0.05). Negative correlation was found between T1rho-4-SD fibrotic size and LV ejection fraction ( r = −0.49, p = 0.11). T1rho-4-SD fibrotic size showed positive correlation with NYHA class ( r = 0.46, p = 0.13). Conclusions T1rho CMR has potential to detect fibrosis in HCM patients. 4-SD may be the appropriate threshold for assessment.
Abstract Objectives This study investigated whether chronic low-level tragus stimulation (LL-TS) inhibits cardiac sympathetic remodeling and reduces ventricular arrhythmia inducibility in a ...post-infarction canine model. Background Low-level vagal stimulation has been shown to suppress cardiac sympathetic activity, which plays an important role in ventricular arrhythmia after myocardial infarction (MI). Our previous studies reported a noninvasive approach to deliver vagal stimulation by transcutaneous stimulation at the tragus, where the auricular branch of the vagus nerve is located. Methods Twenty-two beagles were randomized to the normal control (n = 6), MI (left anterior descending coronary artery ligation without LL-TS n = 8), and TS (MI plus LL-TS n = 8) groups. LL-TS was delivered 2 h each day at 80% below the threshold which slowed sinus rate. Results At 2-month follow-up, LL-TS was found to significantly reduce ventricular arrhythmia inducibility (arrhythmia score: 1.8 ± 0.8 vs. 3.6 ± 0.7, p < 0.01, compared to the MI group), decreased left stellate ganglion (LSG) activity (frequency: 32 ± 15 vs. 112 ± 29 impulses/s; and amplitude: 0.15 ± 0.12 mV vs. 0.38 ± 0.12 mV, compared to MI group), and attenuated cardiac sympathetic remodeling induced by chronic MI. The nerve growth factor (NGF) protein was down-regulated, whereas the small conductance calcium-activated potassium channel type2 (SK2) protein was up-regulated in the LSG by chronic LL-TS. Conclusions Chronic LL-TS could reduce the ventricular arrhythmia inducibility, LSG neural activity and sympathetic neural remodeling in a post-infarction canine model. Down-regulation of NGF protein and up-regulation of SK2 protein in the LSG contribute to the salutary effects of LL-TS.
Abstract Background The autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF), and modulation of the ANS function may contribute to AF ...control. Methods Anesthetized dogs received either sham treatment (SHAM group, n = 8) or low-level carotid baroreceptor stimulation (LL-CBS) treatment (LL-CBS group, n = 8). The stimulation voltage was set at 80% below the threshold. To simulate focal AF, high-frequency stimulation (HFS) was applied to local nerves during the atrial refractory period. Multielectrode catheters were attached to the atria and all the pulmonary veins to determine the changes in the AF threshold (AF-TH), the atrial effective refractory period (AERP), and the window of vulnerability (WOV) during HFS in both groups. Microelectrodes were inserted into the anterior right ganglionated plexus (ARGP) to record neural firing. Results HFS induced sinus rate (SR) slowing in the superior left ganglionated plexus (SLGP). LL-CBS induced a progressive increase in AF-TH and AERP at all sites and a significant decrease in the sum of WOV at 2 hours (all P < 0.05). LL-CBS inhibited the ability of SLGP stimulation to slow the SR and the mean values of frequency and amplitude of ARGP neural activity compared with the SHAM group (all P < 0.05). Conclusions LL-CBS suppressed AF inducibility by inhibiting the neural activity of ganglionated plexuses. LL-CBS may serve as a novel therapeutic modality to treat AF.
There has been no report regarding the impact on male sexual life or sexual function by changes in lifestyle during the coronavirus disease 2019 (COVID-19) epidemic.
To investigate the changes in ...sexual life and sexual function of Chinese men during the COVID-19 epidemic.
An online questionnaire was created and the survey was administered through social media to Chinese adult men.
The main end point was the deteriorated erectile function or ejaculatory control ability, defined by self-evaluation or by decreased International Index of Erectile Function-5 items (IIEF-5) scores or increased premature ejaculation diagnostic tool (PEDT) scores.
Altogether, 612 questionnaires were collected. About 322 (52.6%) subjects were unmarried. About 8.4% and 8.5% subjects reported deteriorated erectile function or ejaculation control ability by self-evaluation, whereas 31.9% and 17.9% subjects showed decreased IIEF-5 scores or increased PEDT scores. Subjects with deteriorated erectile function by self-evaluation and decreased IIEF-5 scores had higher General Anxiety Disorder-7 (P < .001 and P = .001) and higher Patient Health Questionnaire-9 score (P < .001 and P = .002) after the epidemic, decreased frequency of sexual life (P < .001 and P < .001) and physical exercise (P = .009 and .007) after the epidemic. Subjects with deteriorated ejaculation control ability by self-evaluation and increased PEDT scores had higher General Anxiety Disorder-7 (P < .001 and P < .001) and higher Patient Health Questionnaire-9 score (P < .001 and P = .002) after the epidemic. Subjects with decreased frequency of sexual life had reduced income (P < .001), increased anxiety (P < .001) and depression (P < .001). Married subjects had higher proportion of improved depression (P = .048) and increased frequency of sexual life (P = .010).
During the COVID-19 epidemic, decreased sexual function was present in a certain proportion of adult men, and the risk factors include increased anxiety and depression, and decreased frequency of sexual life.
Fang D, Peng J, Liao S, et al. An Online Questionnaire Survey on the Sexual Life and Sexual Function of Chinese Adult Men During the Coronavirus Disease 2019 Epidemic. Sex Med 2021;9:100293
Purpose This study sought to introduce 3-dimensional (3D) virtual surgical planning and digital rapid-prototyping templates for zygomaticomaxillary complex (ZMC) injuries associated with orbital ...volume change and to evaluate the surgical outcomes quantitatively. Patients and Methods Eight patients who underwent open reduction and fixation for a ZMC injury with orbital volume change were studied. Computed tomographic (CT) scan of the zygomaticomaxillary area was performed before the operation in each case. Scanned data were converted into 3D models using Mimics software (Materialise, Brussels, Belgium) for surgical designs. Virtual surgical reductions and correlated guiding templates were designed using Mimics and Magics software (Materialise). The operations were performed with the help of prefabricated templates to reduce the fractures. A postoperative CT scan of each patient was obtained within 2 weeks after surgery, and quantitative measurements were made to assess the surgical outcomes. Preoperative volumes of the bilateral orbits were compared, and concordance with postoperative volumes of the bilateral orbits was assessed. Twenty-one pairs of distances from 7 marker points to 3 reference planes were measured to assess postoperative facial symmetry. Results Volumes of the injured orbits were significantly different from volumes of the uninjured orbits preoperatively ( P < .05), whereas bilateral orbital volumes showed no statistically significant difference postoperatively ( P > .05). In addition, 19 of the 21 pairs of bilateral distances showed no significant difference postoperatively ( P > .05). Conclusions Quantitative assessment showed that digitally designed, rapid-prototyping templates for ZMC fractures have a positive impact on restoring facial symmetry and concordance of bilateral orbital volumes.
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