Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

AIM: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS: Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

Pairwise comparison of 18F-FDG and 18F-FCH PET/CT in prostate cancer patients with rising PSA and known or suspected second malignancy.

OBJECTIVE: This study aimed to evaluate the usefulness of combining fluorine-18 choline (F-FCH) and fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in patients with rising prostate-specific antigen and known or suspected second malignancy. MATERIALS AND METHODS: F-FCH and F-FDG PET/CT were performed 15±9 days apart on the same PET/CT system and acquisition and reconstruction parameters. A mean standardized uptake value (SUVmean) was computed for every lesion that could be discriminated with both tracers. PET results were confirmed by histology (eight patients) and clinical and imaging follow-up (mean±SD: 15±9 months). RESULTS: Of 77 consecutive patients who underwent F-FCH PET/CT scans for suspected prostate cancer recurrence, 10 (13%) were suspected to have a second malignancy because of F-FCH PET pattern inconsistency with that of prostate cancer (n=6), because of a history of a second malignancy with similar metastatic patterns (n=2) or inconsistency between disease burden and prostate-specific antigen value (n=2). Seventy lesions were studied, with a final diagnosis of prostate cancer, other cancers and benign disease in 55, nine and six lesions, respectively. F-FCH SUVmean and F-FCH/F-FDG SUVmean ratios were significantly different between prostate cancer, nonprostate cancer and benign disease (P<0.0001 and P=0.04, respectively). Receiving operating characteristic analysis showed that the F-FCH/F-FDG ratios were not better than F-FCH SUVmean in discriminating prostate cancer from nonprostate cancer and benign diseases (sensitivity, specificity and area under the curve were 69%, 80%, 0.71 and 84%, 80% and 0.89, respectively). CONCLUSION: We found that F-FCH/F-FDG SUVmean ratios cannot differentiate prostate cancer recurrences from other cancer types when both diagnoses are suspected. Doubtful lesions should be biopsied.

Eye motion increases temporal visual field extent.

PURPOSE: To study the impact of eye motion on visual field extent. METHODS: Visual fields were tested in 15 healthy volunteers with the Goldmann perimeter using a V4 test object, from seen to unseen, first in primary position of gaze, then allowing eye motion. Temporal points falling out of the cupola were tested again after a controlled nasal head rotation using a headband prototype fitted with a line-laser level having two orthogonal vial levels. Visual field surface areas (cm(2) ) were calculated as projections on a 30-cm virtual Goldmann cupola, whose extent would have been large enough to include all points. Reproducibility error of the method assessed by calculation of the relative difference between surface areas of 12 visual field tests and 12 visual field retests was estimated at 14%. Hertel exophthalmometry was recorded to study the influence of globe position on visual field extent. RESULTS: Binocular visual field surface area increased by 37% with eye motion (p-value=1.20·10(-9) ). This increase was highest (46%; p-value=1.2·10(-24) ) in the temporal quadrant. Median maximal visual field temporal eccentricity with eye motion was 128.3° (minimum: 109.5°; maximum: 137.7°) and more than 135° in four eyes of three subjects. Hertel exophthalmometry was positively linked to visual field temporal surface area with eye motion (p-value=0.013). CONCLUSIONS: Eye motion greatly expands the temporal visual field. This peculiarity is likely an adaptation to terrestrial life with upright bipedal locomotion and may save head movements through horizontal eyeball scanning.

Viral epidemiology and severity of respiratory infections in infants in 2009: a prospective study.

BACKGROUND: Viral respiratory infections are common in infants and can be severe. The new pandemic influenza virus H1N1v2009 was feared to cause particularly severe outcomes. OBJECTIVE: This study aimed at evaluating the impact of H1N1v2009 on the viral epidemiology, the clinical presentation and the severity of respiratory infections in infants. PATIENTS AND METHODS: This prospective epidemiologic study included all infants <2 years of age, both inpatients and outpatients, presenting with respiratory symptoms, from November 2009 through April 2010, at the pediatric emergency department of the University Hospital of Caen, France. A nasal swab was taken for viral detection and analyzed by immunofluorescence and, if negative, polymerase chain reaction. Severe respiratory infection was defined by a score of respiratory severity. RESULTS: One thousand twenty-one infectious episodes with a respiratory sample met inclusion criteria. Eight hundred thirty-four samples (81.7%) were positive. The viruses with the highest incidence were the respiratory syncytial virus (34.2%), the rhinoviruses (23.9%), the coronaviruses (9.3%) and H1N1v2009 (7.7%). Of all infections, 28.6% were severe and more frequent in infants with risk factors. H1N1v2009 infections had a low risk of severe respiratory disease (odds ratios = 0.15) and hospitalization (odds ratios = 0.40) compared with the other viruses. Respiratory syncytial virus infections had a high risk of respiratory severity (odds ratios = 7.85) and were responsible for 71.4% of admissions to the intensive care unit. CONCLUSION: Despite the modest impact of H1N1v2009 observed in this study, further surveillance is needed to detect virological factors that may increase its severity.

Vascular access sites for acute renal replacement in intensive care units.

BACKGROUND AND OBJECTIVES: Several temporary venous catheterizations are sometimes required for acute renal replacement therapy (RRT) in the intensive care unit (ICU). This study compares first and second catheterizations in the femoral and jugular veins in terms of patient safety. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A crossover study from the catheter-dialysis randomized study (Cathedia), which was conducted among 736 critically ill adults requiring RRT, was performed. Catheter insertion complications, catheter-tip colonization, catheter dysfunction and urea reduction ratio (URR) were analyzed considering the crossover and longitudinal designs. RESULTS: This study analyzed 134 patients who underwent two different sites of catheterization, 57 and 77 of whom were initially randomized in the femoral and jugular site, respectively. Using anatomic landmarks, time to insert a femoral catheter was shorter (P=0.01) and more successful (P=0.003) compared with catheterization in the jugular site. Time to catheter-tip colonization at removal was not significantly different between the two sites of insertion (median, 14 days in both groups; hazard ratio, 0.99; 95% confidence interval, 0.61-1.59; P=0.96), as well as time to dysfunction. URRs were analyzed from 395 dialysis sessions (n=48 patients). No significant difference (P=0.49) in mean URR was detected between sessions performed through femoral (n=213; 50.9%) and jugular (n=182; 49.5%) dialysis catheters. CONCLUSIONS: These results validate prior results of this study group and extend external validity to the second catheter used for RRT in the ICU. Femoral and internal jugular acute vascular access sites are both acceptable for RRT therapy in the ICU.

Continuous renal replacement therapy may increase the risk of catheter infection.

BACKGROUND AND OBJECTIVES: Little is known about the risks of catheter-related infections in patients undergoing intermittent hemodialysis (IHD) as compared with continuous renal replacement therapy (CRRT) techniques. We compared the two modalities among critically ill adults requiring acute renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the multicenter Cathedia study cohort of 736 critically ill adults requiring RRT. Cox marginal structural models were used to compare time to catheter-tip colonization at removal (intent-to-treat, primary endpoint) among patients who started IHD (n = 470) versus CRRT (n = 266). On-treatment analysis was also conducted to take into account changes in prescription of RRT modality. RESULTS: Hazard rate of catheter-tip colonization did not increase within the first 10 days of catheter use. Predictors of catheter-tip colonization were higher lactate levels and hypertension, while systemic antibiotics, antiseptics-impregnated catheters, and mechanical ventilation were associated with decreased risk. The incidence of catheter-tip colonization per 1000 catheter-days was 42.7 in the IHD group and 27.7 in the CRRT group (P < 0.01). This association was no longer significant after correction for channeling bias (weighted HR, 0.96; 95% CI: 0.77 to 1.20, P = 0.73). On-treatment analysis revealed an increased risk of primary endpoint during CRRT exposure as compared with IHD exposure (weighted HR, 0.71; 95% CI: 0.56 to 0.92, P < 0.009). CONCLUSIONS: Our results do not support the use of CRRT when IHD could be an alternative to reduce the risk of catheter-related infection.