Effect of cardiac resynchronization therapy on cardiotrophin-1 circulating levels in patients with heart failure

Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines. Plasma CT-1 levels correlate with the left ventricle mass index in patients with dilatated cardiomyopathy and congestive heart failure (CHF). The aim of this paper was to evaluate CT-1 plasma levels, before and after cardiac resynchronization therapy CRT, and to characterizeits prognostic role in patients with CHF. Fifty-two consecutive patients (M/F = 39/13; 56 ± 11 years old) underwent clinical and echocardiographic evaluation, and blood sample collection at baseline. The same evaluation was repeated 6.4 ± 0.79 months after CRT. Patients with a decreased LV end-systolic volume by at least 15% (reverse remodeling) were considered echo responders to CRT. Twenty-nine patients (56%) were responders to CRT. After CRT, only 15 patients (29%) showed increased CT-1 after CRT. They were all non responders to CRT. A multivariate, logistic modelshowed CT-1 as an independent predictor of CRT echo response (p = 0.005; OR 0.97). During follow-up (18 ± 7 months), 21 cardiac events in 18 patients occurred. A Cox multivariable model showed plasma BNP pre-CRT (p = 0.02; CI 1.2–5.6; OR 3.1) and CT1 post-CRT (p = 0.01; CI 1.4–4.3; OR 2.7) as independent predictors of cardiac events. Analysis of CT-1 plasma levels deserves future consideration for larger, longitudinal studies in patients with CHF.     

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.     

Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions

PurposeTo assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction).Methods and materialsPatients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1–T2 pN0–N1a) invasive ductal carcinoma.Results77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged “good/excellent” and “poor” in 75 (97%) and in 2 (3%) patients, respectively.Conclusions40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.     

Predictors of Health-related Quality of Life and Adjustment to Prostate Cancer During Active Surveillance

Background

Active surveillance (AS) is emerging as an alternative approach to limit the risk of overtreatment and impairment of quality of life (QoL) in patients with low-risk localised prostate cancer. Although most patients report high levels of QoL, some men may be distressed by the idea of living with untreated cancer.

Objective

To identify factors associated with poor QoL during AS.

Design, setting, and participants

Between September 2007 and March 2012, 103 patients participated in the Prostate Cancer Research International Active Surveillance (PRIAS) QoL study. Mental health (Symptom Checklist-90), demographic, clinical, and decisional data were assessed at entrance in AS. Health-related QoL (HRQoL) Functional Assessment of Cancer Therapy-Prostate version and Mini-Mental Adjustment to Cancer outcomes were assessed after 10 mo of AS.

Outcome measurements and statistical analysis

Multivariate logistic regression models were used to identify predictors of low (<25th percentile) HRQoL, adjustment to cancer, and a global QoL index at 10 mo after enrolment.

Results and limitations

The mean age of the study patients was 67 yr (standard deviation: ±7 yr). Lack of partner (odds ratio [OR]: 0.08; p = 0.009) and impaired mental health (OR: 1.2, p = 0.1) were associated with low HRQoL (p = 0.006; area under the curve [AUC]: 0.72). The maladaptive adjustment to cancer (p = 0.047; AUC: 0.60) could be predicted by recent diagnosis (OR: 3.3; p = 0.072). Poor global QoL (overall p = 0.02; AUC: 0.85) was predicted by impaired mental health (OR: 1.16; p = 0.070) and time from diagnosis to enrolment in AS <5 mo (OR: 5.52; p = 0.009). Influence of different physicians on the choice of AS (OR: 0.17; p = 0.044), presence of a partner (OR: 0.22; p = 0.065), and diagnostic biopsy with >18 core specimens (OR: 0.89; p = 0.029) were predictors of better QoL. Limitations of this study were the small sample size and the lack of a control group.

Conclusions

Factors predicting poor QoL were lack of a partner, impaired mental health, recent diagnosis, influence of clinicians and lower number of core samples taken at diagnostic biopsy. Educational support from physicians and emotional/social support should be promoted in some cases to prevent poor QoL.