Contributions to hepatic fibrosis in HIV-HCV coinfected and HCV monoinfected patients

OBJECTIVES: The aim of this study was to further explore the severity of liver disease and its predictors in a cohort of hepatitis C virus (HCV) infected patients, some of whom were coinfected with the human immunodeficiency virus (HIV). METHODS: This is a retrospective, cross-sectional study of patients undergoing liver biopsy to stage HCV disease prior to consideration of anti-HCV therapy. RESULTS: A total of 92 HIV-HCV coinfected and 372 HCV monoinfected patients were included. As might be expected, coinfected patients differed from monoinfected patients in a number of ways, including having lower body mass index (BMI), and lower alcohol intake. Liver disease was very similar between the two groups, with mean fibrosis score of 1.45 u for coinfected and 1.53 u for monoinfected (p = NS). Histological inflammation score dominated multivariate models of fibrosis when it was included in them. When only clinical predictors were used in multivariate models, BMI and type 2 diabetes had independent associations in monoinfected patients, whereas low CD4 count, current or nadir, was the only variable with an independent association in coinfected patients. CONCLUSIONS: Coinfected patients do not have uniformly worse liver disease than monoinfected patients. Immune compromise plays an important role in liver disease in coinfected patients, and the role of other clinical factors in liver disease may differ between these two groups, as well.     

Risk factors for initial surgery in pediatric patients with Crohn's disease

BACKGROUND & AIMS: The cumulative incidence of surgery ranges from 40%-70% at 10 years from the time of diagnosis of Crohn's disease in adults. We retrospectively determined the cumulative incidence of and risk factors for surgery (intestinal resection) in pediatric patients with Crohn's disease. METHODS: Uniform data from 989 consecutive Crohn's disease patients (age 0-17 years at diagnosis), collected from 6 different pediatric centers between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry, were analyzed. RESULTS: Median follow-up time was 2.8 years (range, 1 day to 16.7 years). One hundred twenty-eight patients underwent surgery. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 17% at 5 years and 28% at 10 years from the diagnosis of inflammatory bowel disease. Univariate Cox proportional hazards models showed leukocytosis (2.85 [hazard ratio]; P = .02), hypoalbuminemia (3.41; P = .05), and anti-Saccharomyces cerevisiae antibody (ASCA) positivity (3.43; P = .05) were associated with increased risk for surgery. Multivariate Cox models showed female gender (1.49; P = .03), initial diagnosis of ulcerative colitis (3.63; P < .0001), poor growth at presentation (2.16; P = .007), and abscess (1.90; P = .009), fistula (2.30; P = .0005), or stricture (3.41; P < .0001) development were associated with increased risk for surgery. Age 3-5 years (0.26; P = .01) or 6-12 years (0.62; P = .01) at diagnosis, fever at presentation (0.50; P = .03), and treatment with infliximab (0.36; P = .0005) or 5-aminosalicylic acid (0.44; P < .0001) were associated with decreased risk for surgery. CONCLUSIONS: Risk stratification during the course of Crohn's disease in pediatric patients will help to guide therapy that may improve the natural history of disease and decrease the need for surgery.     

Double-delayed intensification improves event-free survival for children with intermediate-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Addition of a delayed-intensification (DI) phase after standard induction/consolidation therapy was previously shown to improve outcome for patients younger than 10 years of age with intermediate-risk acute lymphoblastic leukemia (ALL). The current trial randomized 1204 patients to regimens containing a single DI phase (405 patients), 2 DI phases (DDI) (402 patients), or a single DI phase in conjunction with increased vincristine and prednisone pulses during maintenance (DIVPI) (397 patients). Estimates of event-free survival (EFS) and survival at 6 years are 79% +/- 1% and 89% +/- 1%, respectively. EFS was improved on DDI compared with either DI (log-rank P =.04; Kaplan-Meier [KM] P =.04; relative risk [RR] = 1.38) or DIVPI (log-rank P =.04; KM P =.01; RR = 1.39).There was no difference in EFS for the DI and DIVPI regimens (log-rank P =.96; KM P =.75). Survival estimates at 6 years were 87% (SD = 2%) for DI; 91% (SD = 2%) for DDI; and 90% (SD = 2%) for DIVPI (P =.17). Significant univariate risk factors for the overall cohort included poor day-7 marrow response, black race, and age of at least 5 years. These data demonstrate that DDI improves EFS of patients younger than 10 years of age with intermediate-risk ALL.     

Submaximal early exercise test compared to clinical findings for evaluation of short- and long-term prognosis after the first myocardial infarction

Clinical and ergometric data were derived from 1098 consecutiveexercise tests in patients with a first acute myocardial infarctionbetween 1974–1983. In 1992 a follow-up was performed inorder to analyse the importance of a submaximal early exercisetest, in combination with clinical data, for the predictionof short- and long-term prognosis of cardiovascular death. The relative value of 20 clinical variables, including medicalhistory, markers of infarction size, medication etc., and 28variables at exercise test were studied. Univariate, multivariateand survival analysis, for estimation of prognosis and independentprediction of cardiovascular death was used. Independent clinical risk factors for cardiovascular death were(1) Within 1 year: relative heart volume (ml.m^–2 bodysurface area) on chest X-ray. (2) Long-term mortality: maximumheart rate and relative heart volume, diabetes, age and digitalismedication. Independent exercise risk factors were: (1) Within1 year: heart rate, ventricular arrhythmia and ST depression 1 mm before exercise, diastolic blood pressure at maximum exerciseand target heart rate. (2) Long-term mortality: angina pectorisand/or ST depression 1 mm at maximum exercise. In subgroupsof patients with clinical risk factors, mortality risk increasedif there were signs of angina pectoris and/or ST depression 1 mm during exercise. The risk increased 100% in diabetics,91% with age >70 years, 58% with relative heart volume 500ml.m^–2 body surface area, 42% with heart rate 100 atadmission, and 34% with digitalis medication. No increase wasfound in the subgroup of patients without clinical risk factors. Thus, submaximal early exercise stress testing provides importantinformation for short- and long-term prognosis in patients afterthe first acute myocardial infarction compared to clinical evaluationalone.     

Association of chromosome arm 9p abnormalities with adverse risk in childhood acute lymphoblastic leukemia: A report from the Children's Cancer Group.

Cytogenetic abnormalities of chromosome arm 9p occur frequently in children with acute lymphoblastic leukemia (ALL). We analyzed 201 such cases (11%) in 1,839 children with newly diagnosed ALL treated between 1989 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG). The majority of patients (131; 65%) with a 9p abnormality were classified as higher risk. Nearly all patients had complex karyotypes; most cases had deletions of 9p, add/der(9p), a dicentric involving chromosome arm 9p, and/or balanced translocations and inversions involving 9p. Event-free survival (EFS) estimates at 6 years for patients with and without a 9p aberration were 61% (standard deviation [SD] = 5%) and 76% (SD = 2%; P <.0001). In addition, patients with a 9p abnormality had an increased cumulative incidence of both marrow (P =.04) and central nervous system (P =.0001) relapses. Overall survival also was significantly worse for patients with an abnormal 9p (P <.0001). These effects were most pronounced in standard-risk patients (age 1 to 9 years with white blood cell count <50,000/microL): 6-year EFS of 61% (SD = 9%) versus 80% (SD = 2%; P <.0001). Also, a 9p aberration was an adverse risk factor for B-lineage, but not T-lineage patients. The effect of 9p status on EFS was attenuated, but maintained in a multivariate analysis of EFS after adjustment for Philadelphia chromosome status, age, white blood cell (WBC) count, sex, race, and ploidy group (P =.01). Thus, abnormalities of chromosome arm 9p identify a subgroup of standard-risk patients with increased risk of treatment failure.     

Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group

We have determined the prognostic significance of hypodiploidy (<46 chromosomes) in a large cohort of children with acute lymphoblastic leukemia (ALL) treated by the Children's Cancer Group. Among 1,880 patients, 110 (5.8%) had hypodiploid karyotypes: 87 had 45 chromosomes, 15 had 33 to 44 chromosomes, none had 29 to 32 chromosomes, and 8 had 24 to 28 chromosomes (near-haploidy). Six-year event-free survival (EFS) estimates for patients with 45 chromosomes, 33 to 44 chromosomes, or 24 to 28 chromosomes were 65% (standard deviation [SD], 8%), 40% (SD, 18%), and 25% (SD, 22%), respectively (log rank, P =.002; test for trend, P =.0009). The combined hypodiploid group had worse outcome than nonhypodiploid patients, with 6-year EFS of 58% (SD, 7%) and 76% (SD, 2%), respectively (P <.0001). EFS for the subgroup with 45 chromosomes was similar to that of patients with pseudodiploidy (P =.43) or 47 to 50 chromosomes (P =.76). None of the patients with 24 to 28 chromosomes had a t(4;11), a t(9;22), or a t(1;19), and most received highly intensive therapy. The adverse risk associated with 33 to 44 and 24 to 28 chromosomes remained significant in multivariate analyses adjusted for important risk factors including age, white blood cell count, and Philadelphia chromosome status. Thus, hypodiploidy with less than 45 chromosomes, particularly 24 to 28 chromosomes, is a significant adverse risk factor despite treatment with contemporary intensive therapies.     

Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.

Monosomy 7 or deletions of 7q are associated with many myeloid disorders; however, the significance of such abnormalities in childhood acute lymphoblastic leukemia (ALL) is unknown. Among 1880 children with ALL, 75 (4%) had losses involving chromosome 7, 16 (21%) with monosomy 7, 41 (55%) with losses of 7p (del(7p)), 16 (21%) with losses of 7q (del(7q)), and two (3%) with losses involving both arms. Patients with losses involving chromosome 7 were more likely to be > or =10 years old, National Cancer Institute (NCI) poor risk, and hypodiploid than patients lacking this abnormality. Patients with or without these abnormalities had similar early response to induction therapy. Event-free survival (EFS) and survival for patients with monosomy 7 (P<0.0001 and P=0.0007, respectively) or del(7p) (P<0.0001 and P=0.0001, respectively), but not of patients with del(7q), were significantly worse than those of patients lacking these abnormalities. The poorer EFS was maintained after adjustment for a Philadelphia (Ph) chromosome, NCI risk status, ploidy, or an abnormal 9p. However, the impact on survival was not maintained for monosomy 7 after adjustment for a Ph. These results indicate that the critical region of loss of chromosome 7 in pediatric ALL may be on the p-arm.     

In Vitro Elution Characteristics of Vancomycin in a Composite Calcium Phosphate/Calcium Sulfate Bone Substitute

Background

Periprosthetic joint infection is a particularly difficult orthopedic problem, complicating a growing number of revision procedures. Joint debridement and systemic antibiotics are the mainstay of treatment, yet difficulty remains in maintaining a minimum inhibitory concentration of antibiotic at the localized site of infection.

Study Aims

This study analyzes the elution characteristics of a 40%bwt calcium phosphate–60%bwt calcium sulfate composite, at varying concentrations of vancomycin.

Methods

Four groups of varying concentrations of vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the composite cement. At designated time intervals up to 28 days, the antibiotic concentration was detected using fluorescence polarization immunoassay and the elution trends compared.

Results

The elution rate of each of the four groups decreased over time. At almost all of the intervals, the elution rates of the higher concentration groups were significantly higher than the lower concentration groups (P < 0.05).

Conclusions

Calcium sulfate reabsorbs over a prolonged period, producing porosity which allows for new bone ingrowth through occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts as a long-term osteoconductive matrix.

Clinical Relevance

The results of this study suggest that vancomycin can be mixed affectively with a calcium sulfate/phosphate composite, both maintaining stability and eluting gradually over a clinically relevant period of time.