Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion

The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.     

青少年中的低度炎症反应、肥胖和胰岛素抵抗

多项研究显示成人中2型糖尿病常在机体免疫系统发生各种亚临床和慢性激活后出现.特异性急性蛋白,细胞因子和趋化因子血浓度升高以及脂肪因子脂联素降低能预示2型糖尿病的发生.即便在校正传统危险因素的影响后,低度炎症反应和2型糖尿病依然显著相关,因此前者很可能与后者的发病机制有关.但是,脂肪组织所分泌的诸多细胞因子和趋化因子本身即是2型糖尿病的危险因素,因而也可用肥胖来解释免疫介质升高和糖尿病间的某些关系.     

Clinical grade cell manipulation

In the past decade, a new form of therapy based on biological rather than pharmacological intervention has been developed. The term 'cell therapy', as applied to this new therapeutic tool, means the administration of living, non-germline somatic cells to humans for diagnostic or therapeutic purposes. Cell therapy products (CTPs) are generated by ex vivo processes, which comprise cell harvesting from patients or healthy donors, in vitro manipulation and administration of the manipulated cells to patients. The aim of ex vivo processes is to obtain cell subsets with defined functional properties that are capable of replacing or repairing damaged tissues or organs. Some examples of cell therapy are transplantation of expanded haematopoietic stem cells (HSCs), adoptive immunotherapy and dendritic cell vaccination to augment or restore the immune response for the treatment of malignant or infectious diseases. The types of cells most frequently used for cell therapy include haematopoietic pluripotent progenitor and stem cells from the bone marrow and peripheral blood, T-cell clones and dendritic cells. Although CTPs should be produced according to good manufacturing practice, they differ from traditional pharmaceutical products with regard to quality control and safety aspects. These differences prompted the development of a number of documents issued by regulatory bodies, which specifically address CTPs. This review discusses several issues related to the design, construction and validation of a hospital-based facility for the production of CTPs, the implementation of cell-manipulation processes and quality control of the final products.     

Silent cerebral infarction,income, and grade retention among students with sickle cell anemia

Children with sickle cell anemia have a higher‐than‐expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross‐sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5–15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia. Am. J. Hematol. 89:E188–E192, 2014. © 2014 Wiley Periodicals, Inc.     

Follicular lymphoma grade 3B

Follicular lymphoma (FL) grade 3B (FL3B) is defined as FL with more than 15% centroblasts per high resolution field present as solid sheets. Coexistence with diffuse large B-cell lymphoma (DLBCL) is frequent. In contrast to other FL, FL3B frequently lack CD10 expression (approximately 50% of cases), show lower probability of BCL2 expression (69% positive) and increased TP53 expression (31% positive). The t(14;18) hallmark translocation of FL is present in only around 13% of FL3B. In contrast, translocations affecting the BCL6 locus in 3q27 are frequent (44%). Overall, FL3B in many features resembles DLBCL. The presence of a diffuse component in FL3B has been related to an unfavorable outcome except for pediatric FL3B that presents in 60% of the cases this DLBCL component. In this chapter we sought to review the present knowledge on morphological, cytogenetic and molecular features in FL3B.     

Modified Child-Pugh grade vs albumin-bilirubin grade for predicting prognosis of hepatocellular carcinoma patients after hepatectomy

BACKGROUND Hepatectomy is the main treatment for patients with hepatocellular carcinoma(HCC)and it has a high possibility for long-term cure potential.But the postoperative mortality and recurrence rates remain high.Since the long-term prognosis of HCC patients is strongly linked to liver function,preoperative assessment of liver function is very important for HCC patients.AIM To compare the predictive power of the modified Child-Pugh(MCP)and albumin-bilirubin(ALBI)grades for the long-term outcome of HCC.METHODS From January 2010 to June 2017,a total of 204 patients with HCC who underwent surgery at the Second Affiliated Hospital of Chongqing Medical University were enrolled in this retrospective study.Multivariate Cox regression analysis was used to determine the independent predictive factors of survival and relapse.The area under the curve(AUC)was used to evaluate the discriminative performance of the MCP grade and ALBI grade to predict the postoperative overall survival(OS)time and recurrence-free survival(RFS)time.RESULTS The median OS and RFS times were 44.0 mo(range:22.0-74.0 mo)and 22.0 mo(range:5.0-45.0 mo),respectively.The median OS and RFS times of MCP grades 1,2,and 3 patients were 60.0,39.0,and 18.0 mo(P<0.001)and 36.0,15.0,and 7.0 mo(P<0.001),respectively.The median OS and RFS times of ALBI grades 1,2,and 3 patients were 56.0,26.0,and 6.0 mo(P<0.001)and 25.0,10.0,and 3.0 mo(P=0.003),respectively.Both the MCP and ALBI grades were more accurate than the Child-Pugh grade for predicting long-term prognosis.Further analysis demonstrated that for both predicting OS and RFS,the MCP grade performed better than the ALBI grade(AUC:0.642 vs 0.605 for OS;0.659 vs 0.594 for RFS).CONCLUSION The MCP grade is more accurate than the ALBI grade for predicting long-term outcome of patients with HCC.     

Nuclear morphometry in human pancreatic adenocarcinoma; relation to histological grade, clinical stage, and survival

A retrospective study was performed on 63 pancreatic cancer patients diagnosed during the years 1970-1988. The mean follow-up time of all individual patients was 6.9 months (range 0-37 months). Histological grade, clinical stage, and 12 morphometric nuclear variables were correlated to the survival of patients. Clinical stage (p = 0.066), histological grade (p = 0.095), and morphometric variables (p = 0.155) predicted survival in survival analysis. Clinical stage (p = 0.029), morphometric variables (p = 0.157), and histological grade (p = 0.306) predicted survival at one year after diagnosis. Morphometric variables divided grade II tumours into two prognostically different groups (p = 0.008) when the mean survival time was used as a classifier. Also the metastasizing potential of pancreatic cancer and lymph node involvement were associated with morphometric variables. Histological grade and morphometric variables were positively correlated (p less than 0.001). On the basis of our results, it seems that nuclear morphometric variables are more efficient or equal to subjective histological grade in predicting survival of pancreatic cancer patients. This result suggests the potential use of nuclear morphometric variables in grading pancreatic adenocarcinomas, and selecting patients for different modes of therapy.     

Prostate cancer Tx. Therapeutic options based on tumor grade, life expectancy, and patient preferences

Cancer of the prostate is the most common malignancy in American men. Its incidence is associated with age, race, family history, and life style factors, such as high-fat diets. Some men develop prostate cancer before age 55, but 80% of tumors occur in men older than age 65. For organ-confined prostate cancers, treatment options include observation, radical prostatectomy, external beam or interstitial radiation, and cryoablation. The appropriate therapeutic decision is based on analysis of multiple factors by the physician and the individual patient. Advanced prostate cancer remains incurable, but hormonal manipulation and newer chemotherapeutic regimens offer palliation in later stages of the disease.     

Toward defining grade C pancreatic fistula following pancreaticoduodenectomy: incidence, risk factors, management and outcome

Background: In 2005 the International Study Group for Pancreatic Fistula (ISGPF) created a definition and grading system for pancreatic fistulae (PF) in which grade C denotes the most severe and potentially life-threatening type. Factors and outcomes associated with grade C fistulae have been ill defined. Methods: Systematic searches of PubMed and EMBASE were conducted by two independent reviewers utilizing the keywords 'pancreaticoduodenectomy' (PD) and 'pancreatic fistula'. Inclusion criteria were: (i) a sample of ≥100 patients; (ii) consecutive accrual of all pathologies, and (iii) use of the ISGPF definition and grading system. Quality appraisal and data extraction were performed using pilot-tested templates. Results: Fourteen articles describing a total of 2706 PDs met the study entrance criteria. Pancreatic fistulae occurred in 479 patients (18%) and included 71 grade C PF that were directly responsible for 25 deaths (35% mortality rate). Only two studies analysed risk factors; these found soft pancreatic texture and histology other than adenocarcinoma to be the most common risk factors. Ten studies reported management strategies and indicated that 51% of patients required reoperation. Conclusions: Grade C PF: (i) accounts for 15% of fistulae following PD and has an associated mortality rate of 35%; (ii) occurs most commonly in pathology associated with a soft remnant, and (iii) requires reoperation in approximately one half of patients. The published literature incompletely describes grade C PF.     

Clinical metrology--a future career grade?

Clinical metrologists have been employed in Leeds for the past seven years. They have come to assume increasing responsibility, particularly in the conduct and recording of clinical trials in the rheumatic diseases. Their work can be extended to the planning of trials, practical procedures, and other research activities. Analysis of 20 applications for a post that recently fell vacant at Leeds suggests that many married women, highly qualified professionally, who have completed their families, would welcome the opportunity to return to parttime nursing duties in "social hours". Increased responsibility and job satisfaction provided by the post compensate for a reduction in salary. Clinical metrology may be a new career grade in the National Health Service that allows for more careful monitoring of patients with constancy that cannot be achieved with rotating junior medical staff. Physicians can be released from the routine of follow-up, so that they have more time for diagnosis, management of complex problems, and research.     

Correlation between preoperative inflammatory markers,Ki-67 and the pathological grade of glioma

To investigate the correlation between preoperative inflammatory markers, Ki-67 expression and the pathological grade of glioma, and to provide a reference for clinical prediction of glioma prognosis.A total of 45 glioma patients who underwent surgery with complete clinical and pathological data were in our hospital from January 2012 to December 2018 were enrolled. Glioma was divided into WHO grade I to IV. Forty-five healthy health examiners with matched clinical characteristics were included to the control group. Blood routine tests were recorded at admission in both the glioma and control group. The ratio of neutrophil to lymphocyte cytometry (NLR), derived neutrophil to lymphocyte ratio (dNLR) (white blood cell count – neutrophil count to neutrophil count), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI, serum albumin content + 5 × lymphocyte count) were calculated. The expression of Ki-67 in glioma was detected by immunohistochemistry. The relationship between the above markers, Ki-67 expression and pathological grade of glioma was evaluated with receiver operating characteristics curve analysis and Spearman correlation test. The correlation between the markers and Ki-67 were also determined.NLR, dNLR, PLR were increased in the glioma group (P < .001, <.001, .002), whereas red blood cell distribution width (RDW) was decreased (P = .009). All the glioma samples expressed Ki-67 with varying degree. Receiver operating characteristics curve analysis reveals NLR, dNLR, PLR, and RDW have significant discriminating ability in differentiating the glioma and control sample. NLR, PLR, PNI, and Ki-67 were significantly correlated with glioma pathology grade (P = .023, .006, .019, <.05), while dNLR and RDW were not associated with glioma grade. Finally, NLR and PLR were related to Ki-67 expression in glioma patients (P = .002, .022), while dNLR and RDW were not related to Ki-67 expression.Preoperative inflammatory markers NLR, PLR, PNI, and postoperative Ki-67 expression are associated with pathological grade of glioma. Detection of these markers may aid in better prediction of glioma prognosis.     

Expression of serum human epididymal secretory protein E4 at low grade and high grade serous carcinomas

ObjectiveTo investigate the value of serum human epididymis protein 4 (HE4) in differential diagnosis of patients with low-grade serous (LGSC) and high-grade serous carcinoma (HGSC) serous ovarian cancer.MethodsLGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system, serum levels of HE4 and carbohydrate antigen 125 (CA125) were measured by ELISA and radioisotope method, respectively in 60 serous ovarian cancer patients. HE4 and TP53 protein in cancer tissue were measured by immunohistochemical method.ResultsThe difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue, while serum CA125 did not show significant difference between different serum samples. There was significant difference in serum HE4 levels between LGSC and HGSC, and the result was different within FIGO (I+II) stage, suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HGSC. HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited.ConclusionsHE4 may be a reliable marker for differential diagnosis of LGSC and HGSC. But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.