Brain networks predicting placebo analgesia in a clinical trial for chronic back pain

A fundamental question for placebo research is whether such responses are a predisposition, quantifiable by brain characteristics. We examine this issue in chronic back pain (CBP) patients who participated in a double-blind brain imaging (functional magnetic resonance imaging) clinical trial. We recently reported that when the 30 CBP participants were treated, for 2 weeks, with topical analgesic or no drug patches, pain and brain activity decreased independently of treatment type and thus were attributed to placebo responses. Here we examine in the same group brain markers for predicting placebo responses—that is, for differentiating between posttreatment persistent CBP (CBPp) and decreasing CBP (CBPd) groups. At baseline, pain and brain activity for rating spontaneous fluctuations of back pain were not different between the 2 groups. However, on the basis of brain activity differences after treatment, we identified that at baseline the extent of information shared (functional connectivity) between left medial prefrontal cortex and bilateral insula accurately (0.8) predicted posttreatment groups. This was validated in an independent cohort. Additionally, by means of frequency domain contrasts, we observe that at baseline, left dorsolateral prefrontal cortex high-frequency oscillations also predicted treatment outcomes and identified an additional set of functional connections distinguishing treatment outcomes. Combining medial and lateral prefrontal functional connections, we observe a statistically higher accuracy (0.9) for predicting posttreatment groups. These findings indicate that placebo response can be identified a priori at least in CBP, and that neuronal population interactions between prefrontal cognitive and pain processing regions predetermine the probability of placebo response in the clinical setting.     

Drain amylase value as an early predictor of pancreatic fistula after cephalic duodenopancreatectomy

AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.METHODS: This prospective clinical study included 382 patients with periampullary tumors that were surgically resected at our department between March 2005 and October 2012. A cephalic duodenopancreatectomy (DP) was performed on all patients. Two closed suction drains were placed at the end of the surgery. The highest postoperative DFA value was recorded and analyzed during the first three postoperative days and on subsequent days if the drains were kept longer. Pancreatic fistula (PF) was classified according to the International Study Group of Pancreatic Fistula (ISGPF) criteria. Postoperative complications were defined according to the Dindo-Clavien classification. All data were statistically analyzed. The optimal thresholds of DFA levels on the first, second and third postoperative days were estimated by constructing receiver operating curves, generated by calculating the sensitivities and specificities of the DFA levels. The DFA level limits were used to differentiate between the group without PF and the groups with biochemical pancreatic fistula (BPF) and CRPF.RESULTS: Pylorus-preserving duodenopancreatectomy was performed on 289 (75.6%) patients, while the remaining patients underwent a classic Whipple procedure (CW). The total incidence of PF was 37.7% (grade A 22.8%, grade B 11.0% and grade C 3.9%). Soft pancreatic texture (SPT) was present in 58.3% of patients who developed PF. Mortality was 4.2%. The median DFA value on the first postoperative day (DFA1) in patients who developed PF was 4520 U/L (range 350-99000 U/L) for grade A fistula (BPF) with a SPT and a diameter of the main pancreatic duct (MPD) of ≤ 3 mm. For grade B/C (CRPF), the median DFA1 value was 8501 U/L (range 377-92060 U/L) with a SPT and MPD of ≤ 3 mm. These values were significantly higher when compared to the patients who did not have PF (122; range 5-37875 U/L). The upper limit of DFA values for the first 3 postoperative days in the examined stages of PF were: DFA1 1200 U/L for the BPF and CRPF; DFA3 350 U/L for BPF and DFA3 800 U/L for CRPF. The determined values were highly significant and demonstrated a reliable diagnostic test for both BPF and CRPF.CONCLUSION: DFA1 ≥ 1200 U/L is an important predictive factor for PF of any degree. The trend of DFA3 (decrease of < 50%) compared to DFA1 is a significant factor in the differentiation of CRPF from transient BPF.     

Non-invasive prediction of forthcoming cirrhosis-related complications

In patients with chronic liver diseases,identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies,assessing therapeutic response,and stratifying long-term prognosis.Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases,several non-invasive methods have been developed as alternatives to liver biopsies.Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard.However,non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker.Accordingly,recent studies have focused on assessing the performance of non-invasive methods through longterm,longitudinal,follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis.As a result,current view is that these alternative methods can independently predict future cirrhosis-related complications,such as hepatic decompensation,liver failure,hepatocellular carcinoma,or liver-related death.The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events.In this article,we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature.     

Noninvasive assessment of portal hypertension in cirrhosis: Liver stiffness and beyond

Liver stiffness measurement(LSM)is a good,but still limited tool to noninvasively assess complications and prognosis in patients with advanced liver disease.This review aims to consider the role of LSM for the diagnosis of portal hypertension-related complications and for assessment of prognosis in cirrhotic patients,and to highlight the drawbacks as well as some alternatives for improving the performance.Hence,this field is far from being closed,and deserves more attention.There is still a place for more carefully designed studies to find new,innovative and reliable approaches.     

miR-199b-5p在骨肉瘤中的预测和诊断作用

目的 探索miR-199b-5p在骨肉瘤中的预测和诊断作用。方法 运用RT-PCR方法检测骨肉瘤患者组织中miR-199b-5p和DRAM的表达水平;利用生物信息学预测工具预测miR-199b-5p的靶基因;分析DRAM与miR-199b-5p的表达关系。结果 miR-199b-5p在组织中有表达,和癌旁正常组织相比,肿瘤组织中的miR-199b-5p表达水平显著升高(P < 0.05);miR-199b-5p与患者的性别、发病年龄、病变部位、肿瘤分型和分期无明显关系(P > 0.05)。研究还发现DRAM在各种组织中均有表达,而DRAM mRNA表达在两者中无明显差异,DRAM与miR-199b-5p呈负相关的表达关系。结论 本研究表明miR-199b-5p可以作为骨肉瘤一个诊断标志物,而DRAM可能是miR-199b-5p的调控靶基因。     

Development and internal validation of a prognostic model for survival after debulking surgery for epithelial ovarian cancer

Objective

Predicting survival of patients with epithelial ovarian cancer (EOC) is based on prognosis of the population. Combining prognostic factors could facilitate survival prediction on the level of the individual patient. The aim of this study was to develop a prognostic model to predict five-year disease specific survival in patients with EOC, and to evaluate whether this would add to prediction based on prognosis of the population.

Patients and methods

A retrospective cohort study was performed of all EOC patients treated with primary debulking and adjuvant chemotherapy or neo-adjuvant chemotherapy and interval debulking surgery in three gynaecological-oncologic centres between 1998 and 2010. Primary outcome was 5-year disease-specific survival. We developed a Cox proportional hazard model using the LASSO-method to select the best combination of characteristics from 12 potential predictors and to correct for overfitting. Performance of the model was expressed as calibration and discrimination (c-statistic). A nomogram was developed to increase the clinical applicability of the model.

Results

Of 840 patients with EOC 462 (55%) died within 5 years due to the disease. A combination of FIGO stage, residual tumour after surgery, primary or interval surgery, histology, performance status, age, amount of ascites and a family history suggestive of breast/ovarian cancer best predicted 5-year survival. The final model showed accurate calibration and the c-statistic was 0.71 (95% CI 0.69–0.74).

Conclusions

Five-year survival in all stage EOC patients can be predicted accurately using available characteristics. After external validation the model can be used for counselling of patients.     

Understanding reproducibility of human IVF traits to predict next IVF cycle outcome

Purpose

Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome.

Methods

The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome.

Results

The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae.

Conclusions

The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient’s stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.     

Prediction and prevention of the macrosomic fetus

Fetal macrosomia is associated with significant maternal and neonatal morbidity. In the long term, infants who are large for gestational age are more likely than other infants to be obese in childhood, adolescence and early adulthood, and are inherently at higher risk of cardiovascular and metabolic complications in adulthood. With over one billion adults in the world now overweight and more than 600 million clinically obese, preventing the vicious cycle effect of fetal macrosomia and childhood obesity is an increasingly pertinent issue. Fetal growth is determined by a complex interplay of various genetic and environmental influences. Consequently the prediction of pregnancies at risk of pathological overgrowth is difficult. Many risk factors for fetal macrosomia, such as maternal obesity and advanced maternal age, are also conversely associated with intrauterine growth restriction. Sonographic detection of fetal macrosomia is notoriously fraught with difficulties, with dozens of formulas for estimated fetal weight proposed but few with sufficient sensitivity to alter clinical practice. This calls into question policies of elective delivery based on projected estimated fetal weight cut-offs alone. More recently the identification of markers of fetal adiposity and maternal serum biomarkers are being investigated to improve the antenatal detection of the large for gestational age fetus. Prevention of fetal macrosomia is entirely dependent upon correct identification of those at risk. Maternal weight, gestational weight gain and glycaemic control are the risk factors for fetal macrosomia that are most amenable to intervention, and have potential maternal health benefits beyond pregnancy and childbirth. The ideal method of optimising maternal weight and glucose homeostasis is yet to be elucidated, though a number of promising advances are recently being reported. In this review we outline the contemporary evidence for the prediction and prevention of fetal macrosomia, which is indeed a contemporary dilemma.     

Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: A cohort study based on 994 patients

Introduction

To advise laryngeal carcinoma patients on the most appropriate form of treatment, a tool to predict survival and local control is needed.

Materials and methods

We performed a population-based cohort study on 994 laryngeal carcinoma patients, treated with RT from 1977 until 2008. Two nomograms were developed and validated. Performance of the models is expressed as the Area Under the Curve (AUC).

Results

Unfavorable prognostic factors for overall survival were low hemoglobin level, male sex, high T-status, nodal involvement, older age, lower EQD_2T (total radiation dose corrected for fraction dose and overall treatment time), and non-glottic tumor. All factors except tumor location were prognostic for local control. The AUCs were 0.73 for overall survival and 0.67 for local control. External validation of the survival model yielded AUCs of 0.68, 0.74, 0.76 and 0.71 for the Leuven (n = 109), the VU Amsterdam (n = 178), the Manchester (n = 403) and the NKI cohort (n = 205), respectively, while the validation procedure for the local control model resulted in AUCs of 0.70, 0.71, 0.72 and 0.62. The resulting nomograms were made available on the website www.predictcancer.org.

Conclusions

For patients with a laryngeal carcinoma treated with RT alone, we have developed visual, easy-to-use nomograms for the prediction of overall survival and primary local control. These models have been successfully validated in four external centers.