Single arm,phase two study of low-dose metronomic eribulin in metastatic breast cancer

Background

Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile.

Methods

We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m² administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy.

Findings

We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients.

Interpretation

Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

     

OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI : IV. STUDIES ON THE MECHANISM OF LYSIS BY CELL-BOUND HEMOLYSIN OF RED BLOOD CELLS AND EHRLICH ASCITES TUMOR CELLS

In studies of the mechanism of lysis of red blood cells by washed streptococci with hemolytic activity (cell-bound hemolysin, CBH) no components released spontaneously by RBC or streptococci, or by interaction between these cells, could be found to induce the formation of soluble hemolysin by the streptococci. It was also found that separation of RBC from streptococci even by Millipore filter or a very thin layer of agar could prevent their hemolysis. By means of cellulose columns it was possible to separate RBC from streptococci after a short incubation. RBC thus separated from streptococci with which they had been incubated underwent hemolysis on subsequent incubation at 37°C. By varying the period of incubation prior to separation it was possible to demonstrate the transfer of increasing amounts of hemolysin from streptococci to RBC with increasing periods of incubation. A considerable part of this appeared to be at a constant rate. A theory is presented on the relationship between the streptococcal cell-bound hemolysin and the group of oxygen-stable streptococcal hemolysins, in terms of a transferable hemolytic moiety and binding sites for this moiety on the streptococcal cell, on various molecular species which can act as inducers of the oxygen-stable hemolysins, and on the RBC, with the affinity of the respective binding sites for the hemolytic moiety increasing in that order.     

Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is commonly associated with heart failure. The benefit of cardiac resynchronization therapy (CRT) on atrial remodeling has been demonstrated. However, biventricular pacing did not reduce the global incidence of AF. We evaluated the relationship between CRT response and AF duration. METHODS: We retrospectively analyzed data from 96 patients (59 +/- 15 years; 78% male) who underwent CRT. All patients had class III-IV New York Heart Association (NYHA) symptoms despite maximal medical therapy, left ventricular ejection fraction (LVEF) < or = 35%, QRS >130 ms, and sinus rhythm before implantation. CRT response in patients who survived at six months of follow-up was defined as: (1) no hospitalization for heart failure and (2) improvement of one or more grades in the NYHA classification. RESULTS: CRT responders (n = 54) and non-responders (n = 42) had similar baseline characteristics, including the incidence of persistent AF within six months before implantation. Six months after implantation, when compared to baseline, CRT responders exhibited a significant decrease in left atrial size (47.5 +/- 7.1 mm vs 44.6 +/- 7.7 mm, P < 0.01) and in the incidence of persistent AF (17% vs 2%, P = 0.02). At six months, CRT responders demonstrated shorter mean AF duration (7.5 +/- 43.3 hours vs 48.8 +/- 129.0 hours, P = 0.03) and lower incidence of persistent AF (2% vs 19%, P = 0.004) compared to nonresponders. CONCLUSION: CRT response is associated with a reversal of atrial remodeling and a shorter AF duration.     

Maternal overweight/obesity characteristics and child anthropometric status in Jos,Nigeria

Objective:

This study is to determine the pattern of overweight and obesity and its relationship with childhood anthropometric status in Nigeria.

Materials and Methods:

This cross-sectional study was conducted in Jos, Nigeria. Interviewer administered questionnaire was used in data collection. Maternal and child anthropometric measurements were obtained using standard WHO methods. Child anthropometric Z scores were obtained from WHO Anthroplus while BMI of mothers were also determined. Totally, 262 mother-child pairs were recruited.

Results:

Mean maternal age and mean child age were 30.8 ± 6.3 yrs (15-47 yrs) and 22.3 ± 18.7 months (3-72 months). Prevalence of maternal underweight, overweight and obesity was 4.2% (11/262), 29.4% (77/262) and 25.9% (68/262), respectively. Child overweight/obesity was 5.4% (14/262), severe under-nutrition 5.7% (15/262). Mean maternal BMI was higher in the older, more educated and higher socioeconomic status (SES). Child mean birth-weight, weight-for-age Z-score and BMI-for-age Z-score (BAZ) were higher among mothers with BMI ≥ 25 kg/m². All large-for-age babies were in mothers with maternal BMI ≥ 25 kg/m². Childhood over-nutrition was more common in maternal BMI of ≥25 kg/m². Overall, BAZ was directly related with maternal BMI, maternal age and birth-weight, although it was inversely related with maternal BM I ≥ 25 kg/m².

Conclusion:

Higher BMI is seen in educated and higher SES mothers and this impact on childhood anthropometry.     

Biliary and pancreatic stents

The use of biliary and pancreatic stents has increased significantly during the last 2 decades because of improvements in available endoscopes and endoscopic accessories, as well as better techniques. The number of endoscopists who can successfully complete these demanding procedures has also increased, as have the indications for stent therapy in biliary and pancreatic diseases. Stents are now made in various shapes and configurations from different types of polymers (plastics), various expandable metallic alloys, and bioabsorbable materials. Most of the available data relate to plastic and metallic stents for biliary tract disease; the data for pancreatic disease are fewer and involve a smaller number of patients. This article reviews the most recent available data concerning biliary and pancreatic stents and discusses possible future developments. It does not attempt to cover all data reported in biliopancreatic stent therapy.