Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) μg/L, or ≤100 μg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age—31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31–5.31), age < 30 years (OR 2.30, CI95% 1.16–4.56), and P. aeruginosa (OR 2.09, CI95% 1.04–4.19).     

The use of high dose aprotinin in liver transplantation: the influence on fibrinolysis and blood loss.

Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KIU/h infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72% in the control group versus 16% in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15% was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) although the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (t-PA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p less than 0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50% (5.6 +/- 4.0 vs. 11.2 +/- 8.6 units, p less than 0.005). The blood saving effect was more pronounced in the postanhepatic period (p less than 0.000001). In conclusion high dose aprotinin inhibits hyperfibrinolysis and reduces intraoperative homologous blood requirement. Therefore its routine use in OLT is recommended.     

Hybrid <Superscript>18</Superscript>F–FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

Purpose

Our purpose in this study was to assess the added clinical value of hybrid ¹⁸F–FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).

Methods

In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed.

Results

A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed.

Conclusion

Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

     

Clinical tumor stage is the most important predictor of pathological complete response rate after neoadjuvant chemotherapy in breast cancer patients

Purpose

Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication.

Methods

CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients. The associations between baseline, first follow-up, and longitudinal enumerations of CTCs and CTC-clusters with patient progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models.

Results

CTC and CTC-cluster counts at both baseline and first follow-up were significantly associated with patient PFS and OS. Time-dependent analysis of longitudinally collected samples confirmed the significantly unfavorable PFS and OS in patients with ≥5 CTCs, and further demonstrated the independent prognostic values by CTC-clusters compared to CTC-enumeration alone. Longitudinal analyses also identified a link between the size of CTC-clusters and patient OS: compared to the patients without any CTC, those with 2-cell CTC-clusters and ≥3-cell CTC-clusters had a hazard ratio (HR) of 7.96 [95 % confidence level (CI) 2.00–31.61, P = 0.003] and 14.50 (3.98–52.80, P < 0.001), respectively.

Conclusions

In this novel time-dependent analysis of longitudinally collected CTCs and CTC-clusters, we showed that CTC-clusters added additional prognostic values to CTC enumeration alone, and a larger-size CTC-cluster conferred a higher risk of death in MBC patients.

     

Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases

Purpose

To explore the associations between lifestyle-related factors and tumor-related prognostic factors in women treated for primary breast cancer, and to detect possible differences between the associations in pre- and postmenopausal women.

Methods

Associations between tumor-related prognostic factors, including the composite endpoint risk of recurrence (RoR), body mass index (BMI), comorbidity (Charlson comorbidity index), basic physical functioning (SF-36), physical activity, smoking, and alcohol consumption were examined with binary logistic regression analysis in a national cohort of 4917 women treated for primary breast cancer. In addition, statistical interactions between predictors and menopausal status were assessed in order to determine if their strength differed significantly as a function of menopausal status.

Results

Higher BMI, reduced physical function, reduced physical activity, and greater alcohol consumption were all statistically significantly associated with two or more tumor-related factors indicating a poorer prognosis. Interaction analysis revealed that BMI was significantly stronger associated with RoR among premenopausal women than among postmenopausal women (interaction ip = 0.048). Similarly, a significant association between RoR and physical function was only seen in the premenopausal population (ip = 0.008). This pattern was also seen between RoR and daily alcohol consumption, which only reached statistical significance in the total population and in premenopausal women (ip < 0.001).

Conclusion

Premenopausal women who are overweight and have poorer physical function have poorer prognosis at the time of diagnosis, suggesting the possible relevance of stratifying adjuvant treatment according to guidelines, BMI, and menopausal status.

     

Malignant lesions on mammography: accuracy of two different computer-aided detection systems

We retrospectively compared the accuracy of two computer-aided detection (CAD) systems for the detection of malignant breast lesions on full-field digital mammograms. Mammograms of 326 patients were analyzed (117 patients with breast cancer, 209 negative cases), and each set of cases was read by two CAD systems (Second Look versus AccuDetect Galileo). True-positive fractions per image and case for soft densities, microcalcifications, and total cancers were assessed. Study results showed better overall performance of AccuDetect Galileo (when compared to Second Look) in detecting masses, microcalcifications, and all cancer types, especially in extremely dense breast parenchyma.