Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease.

OBJECTIVES: Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. BACKGROUND: Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects. METHODS: Granulocyte colony-stimulating factor (G-CSF), 10 microg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging. RESULTS: Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 microl to 52.4 +/- 10.4 microl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 microl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline. CONCLUSIONS: Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.     

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.     

Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in Hospitalized Patients

Asymptomatic colonization may contribute to Clostridium difficile transmission. Few data identify which patients are at risk for colonization. We performed a prospective cohort study of C. difficile colonization and risk factors for C. difficile acquisition and loss in hospitalized patients. Patients admitted to medical or surgical wards at a tertiary care hospital were enrolled; interviews and chart review were performed to determine patient demographics, C. difficile infection (CDI) history, medications, and health care exposures. Stool samples/rectal swabs were collected at enrollment and discharge; stool samples from clinical laboratory tests were also included. Samples were cultured for C. difficile, and the isolates were tested for toxins A and B and ribotyped. Chi-square tests and univariate logistic regression were used for the analyses. Two hundred thirty-five patients were enrolled. Of the patients, 21% were colonized with C. difficile (toxigenic and nontoxigenic) at admission and 24% at discharge. Ribotype 027 accounted for 6% of the strains at admission and 12% at discharge. Of the patients colonized at admission, 78% were also colonized at discharge. Cephalosporin use was associated with C. difficile acquisition (47% of patients who acquired C. difficile versus 25% of patients who did not; P = 0.03). β-lactam–β-lactamase inhibitor combinations were associated with a loss of C. difficile colonization (36% of patients who lost C. difficile colonization versus 8% of patients colonized at both admission and discharge; P = 0.04), as was metronidazole (27% versus 3%; P = 0.03). Antibiotic use affects the epidemiology of asymptomatic C. difficile colonization, including acquisition and loss, and it requires additional study.     

Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation

ObjectivesAdequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation.MethodsA retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800).ResultsPatients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001).ConclusionsA ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.     

Naturalistic outcomes for a day‐hospital programme in a mixed diagnostic sample of adolescents with eating disorders

Despite initial data suggesting positive treatment outcomes for adolescent eating disorder day‐hospital programmes (DHPs), existing studies have included limited follow‐up, small samples, and a focus on restricting‐type eating disorders. To address these gaps, we explored naturalistic outcomes for an adolescent eating disorders DHP. Adolescent participants (N = 265) completed measurements at treatment admission, discharge (n = 170), and various lengths of follow‐up (n = 126; M_{follow up} = 278.87 days). Results from multilevel models indicated significant increases in body weight for the anorexia nervosa group throughout treatment and maintenance of increased body weight from discharge to follow‐up. In bulimic spectrum disorders, binge eating and purging significantly decreased from intake to discharge and did not change from discharge to follow‐up. Across the entire sample, eating disorder symptoms decreased from intake to discharge and did not change from discharge to follow‐up. Further, anxiety and depression decreased over the course of treatment and continued to decrease over the follow‐up period. The current investigation represents the first study to explore longitudinal DHP outcomes within adolescent bulimic spectrum eating disorders. Our findings also highlight many challenges inherent in conducting naturalistic research; it is critical that the field continue to develop solutions to the barriers inherent in conducting longitudinal research on eating disorder treatment.     

Residents’ and standardized patients’ perspectives on empathy: Issues of agreement

Objective

We investigated correlations between residents’ scores on the Jefferson Scale of Empathy (JSE), residents’ perceptions of their empathy during standardized-patient encounters, and the perceptions of standardized patients.

Methods

Participants were 214 first-year residents in internal medicine or family medicine from 13 residency programs taking standardized patient-based clinical skills assessment in 2011. We analyzed correlations between residents’ JSE scores; standardized patients’ perspectives on residents’ empathy during OSCE encounters, using the Jefferson Scale of Patient Perceptions of Physician Empathy; and residents’ perspectives on their own empathy, using a modified version of this scale.

Results

Residents’ JSE scores correlated with their perceptions of their own empathy during encounters but correlated poorly with patients’ assessments of resident empathy.

Conclusion

The poor correlation between residents’ and standardized patients’ assessments of residents’ empathy raises questions about residents’ abilities to gauge the effectiveness of their empathic communications. The study also points to a lack of congruence between the assessment of empathy by standardized patients and residents as receivers and conveyors of empathy, respectively.

Practice implications

This study adds to the literature on empathy as a teachable skill set and raises questions about use of OSCEs to assess trainee empathy.     

Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis

Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n = 38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.     

Psychopathological features during childhood and adolescence among adult bipolar patients: A retrospective study

Objective

There are still several concerns regarding the inconsistency in the diagnosis of Bipolar Disorder (BD) in children and adolescents. This study reviews the symptoms of youth admitted to The University of Texas Harris County Psychiatric Center (UT-HCPC) prior to a confirmed diagnosis of BD to elucidate patterns and target symptoms which may facilitate early recognition of BD.

Methods

This is a retrospective review of charts of adult patients with a discharge diagnosis of BD for three consecutive admissions who were also admitted to UT-HCPC as children or adolescents (N = 26). The Kiddie SADS was completed based on each patient’s first admission as a child and last admission as an adult.

Results

Most of the symptoms found in adult BD were present in the child/adolescent subjects at equivalent rates, except for mood elevation, which was less common during childhood and adolescence. In spite of the psychopathological similarity, only 6 (23%) of the subjects were diagnosed with BD as youth.

Conclusion

BD is poorly diagnosed among children and adolescents. Difficulties in the assessment of the youth, as well as particularities in the psychopathology of mood among children and adolescents may account for the low diagnostic rate.