The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between 5-HT(2A) receptor gene variants and neuropsychiatric illness susceptibility also exists. In a classical twin design involving 24 healthy male subjects (6 monozygotic twin pairs and 6 dizygotic twin pairs), we examined the relative contribution of genetic and environmental factors to interindividual variability in cortical 5-HT(2A) receptor binding as measured with [(18)F]altanserin PET imaging. The intraclass correlation coefficients were 0.67 for dizygotic and 0.87 for monozygotic twin pairs. For comparison, the intraclass correlation coefficient was 0.93 in a group of six male healthy subjects examined twice within two weeks with an identical experimental setup. Multivariate analysis was used to separate the phenotypic variance of individuals into additive genetic (heritability) effect (A), shared (family) environment (C), and non-shared (individual-specific) environment (E). Irrespective of whether a full ACE model or a reduced AE model was used to fit the data, the variance due to non-shared environment was below 10% indicating that the contribution of individual specific environmental factors to 5-HT(2A) receptor binding is limited.     

Defining the relative contribution of health care environmental components to patient outcomes in the model of 30-day readmission after coronary artery bypass graft (CABG)

BackgroundPatient outcomes following health care interventions may be dependent on a variety of factors: patient, surgeon, hospital, information technology, and temporal, cultural, and socioeconomic factors, among others. In this study, we characterize the relative contribution of each of these factors using a model of 30-day readmission following coronary artery bypass graft.MethodsThe Healthcare Cost and Utilization Project, the American Hospital Association Annual Health Survey Databases, the Healthcare Information and Management Systems Society, and the Distressed Communities Index from 2010 to 2013 were linked for Florida, Iowa, Massachusetts, Maryland, New York, and Washington. Logistic regression, random forest, decision tree, gradient boosting, k-nearest-neighbors classification, and XGBoost tree models were implemented. Modeling results were compared on the basis of predictive accuracy, sensitivity, specificity, and area under the curve. Decision tree performed best and was selected for further analysis. A gradient-boosted model was used to quantify factor contribution.ResultsThe model had 45,352 patients, 54,096 admissions, and a 16.2% 30-day readmission rate after coronary artery bypass graft. The top 10 predictors were disposition at discharge, number of chronic conditions, total procedures, median household income, adults without high school diplomas, primary payer method, Agency for Healthcare Research and Quality comorbidity: renal failure, patient location (urban-rural), admission type, and age categories. The top 3 socioeconomic predictors were estimated state median household income, adults without high school diplomas, and patient location (urban versus rural designation). The relative contribution of patient/temporal, socioeconomic, hospital information technology, and hospital factors to readmission is 83.45%, 5.71%, 6.34%, and 4.31%, respectively.ConclusionIn this model, the contribution of socioeconomic factors is substantive but lags significantly behind patient/temporal factors. With ever increasing availability of data, identification of contributors to patient outcomes within the overall health care macroenvironment will allow prioritization of interventions.     

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

Background

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival.

Methods

A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan–Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival.

Results

At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5–5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3–5.4, p = .01).

Conclusions

Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.     

Outcome of Judet's quadricepsplasty for knee contractures and the effect of local infiltration of epinephrine on reducing blood loss

Objective: To evaluate the effectiveness of Judet''s quadricepsplasty for treatment of knee contractures and to identify the effect of local infiltration of epinephrine on blood loss associated with this procedure.Methods: A retrospective cohort study was conducted in which all cases of knee contractures managedwith Judet''s quadricepsplasty from 1st January 2009 to 31st December 2013 were included and weredivided into two groups. The epinephrine group included patients who were infiltrated with dilutedepinephrine (1:400,000) along with xylocaine, around the operative field 15 min prior to the incisiontime, while the control group did not receive any infiltration. Judet''s outcome, blood loss, drop in hemoglobin and required blood transfusion were noted for all patients and compared between both groups.Results: Most common preceding pathology identified for the development of knee contractures wasperiarticular fracture while ilizarov application was the most common etiology. Both groups were found similar in all preoperative characteristics except preoperative flexion contracture (p=0.02). All functional outcome measures including Judet''s outcome were similar in both groups. In contrast, duration of surgery (p=0.01), blood loss (p=0.02), drop in hemoglobin (p=0.01) and number of transfusions (p=0.03) were significantly reduced in epinephrine group.Conclusion: Judet''s quadricepsplasty is a useful procedure to increase the range of motion of rigid knees and local infiltration of epinephrine is effective in decreasing the amount of subsequent blood loss and transfusion requirements.