Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study

In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng/mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels.     

Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

Background

The addition of monoclonal antibodies targeting the epidermal growth factor receptor (anti-EGFR Abs) to chemotherapy for metastatic colorectal carcinoma (mCRC) is commonly delayed in the real-world clinical practice, usually because of late RAS testing results.

Objective

To determine whether delayed addition of anti-EGFR mAbs up to the fourth cycle of backbone chemotherapy adversely affected outcomes of mCRC patients treated with first-line regimens.

Patients and Methods

Clinical data of patients with histologically verified, RAS wild-type mCRC treated with first-line systemic therapy regimens containing anti-EGFR mAbs were retrospectively analysed from a national database. Patients were divided into three groups according to the timing of anti-EGFR mAbs addition to the chemotherapy backbone. Cohort A (n?=?401) included patients in whom anti-EGFR mAbs were added to chemotherapy from the first cycle, cohort B (n?=?71) patients with anti-EGFR mAbs added to chemotherapy from the second cycle, and cohort C (n?=?101) patients who had anti-EGFR mAbs added to chemotherapy from the third or fourth cycle.

Results

Three hundred and thirty-six (58.6%) patients received panitumumab and 237 (41.4%) patients received cetuximab. The median progression-free survival (PFS) of the whole cohort was 12.2 months (95% confidence interval [CI] 10.9–13.5), and the median overall survival (OS) was 33.5 months (95% CI 27.6–39.4). The median PFS and OS for patients treated with anti-EGFR mAbs added to chemotherapy were 12.9 (95% CI 11.5–14.3) and 30.6 months (95% CI 25.2–36.1) for cohort A, 9.7 (95% CI 9.1–10.3) and not reached for cohort B, compared to 11.5 (95% CI 9.8–13.2) and 37.9 months (95% CI 28.6–47.3) for cohort C, respectively.

Conclusions

Delayed addition of anti-EGFR mAbs to first-line chemotherapy was not associated with inferior survival or response rates.

     

Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: application of new methodology

Comparisons of duration of response (DoR) and duration of clinical benefit (DoCB) within clinical trials are prone to biases. To address these biases, we used new methodology to prospectively analyze expected DoR and expected DoCB. Objective response rate and clinical benefit rate were calculated for fulvestrant 500 and 250 mg, and used to calculate expected DoR and expected DoCB for each dose group. The ratios for expected DoR and expected DoCB (expected DoR₅₀₀/expected DoR₂₅₀ and expected DoCB₅₀₀/expected DoCB₂₅₀) were then calculated, thereby allowing statistical comparisons of these endpoints between each arm of the COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial. Expected DoRs for fulvestrant 500 and 250 mg were 3.2 and 3.6 months, respectively. The expected DoR ratio between fulvestrant 500 and 250 mg was not statistically significant (0.89; 95 % CI, 0.48–1.67, P = 0.724). The expected DoCBs for fulvestrant 500 and 250 mg were 9.8 and 7.2 months, respectively. The expected DoCB ratio showed that the expected DoCB for fulvestrant 500 mg was significantly improved compared with the expected DoCB for fulvestrant 250 mg (1.36; 95 % CI, 1.07–1.73, P = 0.013). Analysis of the expected DoR and expected DoCB showed fulvestrant 500 mg significantly increased expected DoCB compared with fulvestrant 250 mg in the CONFIRM trial.     

Sex differences in early carotid atherosclerosis (from the community-based Gutenberg-Heart Study)

The objectives of this study were to describe gender differences in intima-media thickness (IMT) in a community-based population study and to define normal IMT values for healthy men and women. In total, 4,814 participants (aged 35 to 74 years; 2,433 men, 2,381 women) from the Gutenberg-Heart Study (GHS) were included. IMT was measured at both common carotid arteries using an edge detection system. Median IMT was 0.62 mm (25th percentile 0.55, 75th percentile 0.70) in women and 0.65 mm (25th percentile 0.57, 75th percentile 0.75) in men and was significantly associated with age (p <0.0001). On multivariate analysis, advanced age, smoking, and arterial hypertension were positively associated with higher IMT in men and women. A subgroup of 1,025 subjects without cardiovascular risk factors or previous cardiovascular disease was analyzed to define normal IMT values. Nomograms were calculated according to age and gender. For each age group, IMT >95th percentile was defined as abnormal. In this subgroup, gender differences in IMT became nonsignificant at older ages. At the age of 35 years, IMT was 0.71 mm in men and 0.61 mm in women at the 95th percentile. In comparison, at the age of 74 years, IMT at the 95th percentile was 0.90 mm in men and 0.89 mm in women. In conclusion, men had higher carotid IMT than women, but predictors of early carotid atherosclerosis were similar across genders. In young subjects without cardiovascular risk factors, normal values for IMT were lower in women compared with men. In contrast, in older subjects, gender differences in IMT became nonsignificant.     

Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities

Reactive oxygen species, such as superoxide and hydrogen peroxide, are generated in all cells by mitochondrial and enzymatic sources. Left unchecked, these reactive species can cause oxidative damage to DNA, proteins, and membrane lipids. Glutathione peroxidase-1 (GPx-1) is an intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. Certain reactive oxygen species, such as hydrogen peroxide, are also essential for growth factor-mediated signal transduction, mitochondrial function, and maintenance of normal thiol redox-balance. Thus, by limiting hydrogen peroxide accumulation, GPx-1 also modulates these processes. This review explores the molecular mechanisms involved in regulating the expression and function of GPx-1, with an emphasis on the role of GPx-1 in modulating cellular oxidant stress and redox-mediated responses. As a selenocysteine-containing enzyme, GPx-1 expression is subject to unique forms of regulation involving the trace mineral selenium and selenocysteine incorporation during translation. In addition, GPx-1 has been implicated in the development and prevention of many common and complex diseases, including cancer and cardiovascular disease. This review discusses the role of GPx-1 in these diseases and speculates on potential future therapies to harness the beneficial effects of this ubiquitous antioxidant enzyme.     

Hyaluronate-iodine complex: a new adjunct for the management of complex sternal wounds after a cardiac operation

A wound-healing agent developed in the European Union is based on the combination of organic hyaluronan with inorganic iodine. The aim of this pilot study was to assess the efficacy and safety of hyaluronate-iodine in the treatment of sternal wounds. Eight patients with sternal wound dehiscence were entered into the study. After debridement, wounds were dressed with gauze soaked in hyaluronate-iodine. In one patient with an epipleural abscess, hyaluronate-iodine was instilled directly into the abscess cavity daily. Complete healing was achieved in 7 patients, and 1 patient underwent a reconstructive operation for wound closure. The mean (SD) length of treatment was 136 (114.2) days. No adverse effects or complications were apparent in this group. Hyaluronate-iodine is safe and effective in healing sternal wound dehiscence. Randomized controlled trials are needed for further validation.     

Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy

BACKGROUND:

Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant chemotherapy modifies the anatomical conditions in the breast and axilla, and thus SLNB remains controversial in patients treated preoperatively. The aim of this study was to demonstrate the reliability and accuracy of this procedure in this particular group of patients.

METHODS:

The retrospective study analyzed medical records of patients diagnosed with primary breast cancer between the years 2005 and 2009. Of the patients treated by neoadjuvant therapy, 343 underwent lymphatic mapping to identify sentinel lymph nodes, and these were included in the analysis.

RESULTS:

The overall detection rate of sentinel lymph nodes was 80.8%. It was strongly influenced by clinical lymph node status (significantly higher success rate in lymph node‐negative patients); higher detection rates were also associated with age <50 years, estrogen receptor positivity, lower proliferation index, and absent lymphovascular space invasion. The false‐negative rate was 19.5% and was only marginally significantly dependent on lymphovascular space invasion. The overall accuracy of the method was 91.5%.

CONCLUSIONS:

By using the present technique, sentinel lymph node biopsy cannot be recommended as a reliable predictor of axillary lymph node status when performed at the authors' institution after neoadjuvant chemotherapy. Infrequent use of blue dye for lymphatic mapping, low number of resected sentinel lymph nodes, and absence of any selection among patients included in the study could be the main factors responsible for the low detection rate and high false‐negative rate. Cancer 2011;. © 2011 American Cancer Society.