Safety Profile of Sequential Transcatheter Chemoembolization with DC Bead?: Results of 237 Hepatocellular Carcinoma (HCC) Patients

Introduction

Complications of chemoembolization performed with DC Bead^? loaded with doxorubicin (DEBDOX) of diameters 100?C300???m and 300?C500???m are presented in this paper. These diameters are currently the smallest available in drug-eluting technology.

Methods

Included are 237 patients who were treated with sequential DEBDOX with doxorubicin loaded at 37.5?mg/ml of DC Bead. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) were used to categorize complications.

Results

Thirty-day mortality was 1.26% (3/237). Incidence of grade 5 complications was 1.26% (3/237). Overall, grade 4 complications resulted in 5.48% (13/237) (irreversible liver failure, cholecystitis). Grade 2 liver function deterioration developed in 10 patients (4.2%). Cholecystitis/grade 2 and 4 incidents were observed in 3.6?C5.06% across sessions (overall 13 patients; 5.48%). Postembolization Syndrome (PES) grade 1 or 2 was observed in up to 86.5%; however, grade 2 was observed in 25?C42.19% across treatments. Pleural effusion was seen in eight patients (overall 3.37%; grade 1 in 1.8?C3.7% across treatments; grade 3 in 0.42%). Grade 1 procedure-related laboratory pancreatitis was seen in 0.45%, and grade 2 gastrointestinal bleeding was seen in 0.84%. Procedure-associated skin erythema/grade 1 was seen in 0.84%. There was no correlation of liver failure or transient liver function deterioration with the diameter of the beads (p?=?0.25?C0.37 and p?=?0.14?C0.89, respectively). Stratifying with the diameter of the beads correlation values was: for cholecystitis (p?=?0.11?C0.96 across treatments), PES (p?=?0.35?C0.83), temporary/grade 1 elevation of liver enzymes (p?=?0.002?C0.0001), and bilirubin (p?=?0.04?C0.99).

Conclusions

DEBDOX chemoembolization is safe and small calibres do not result in increased complication rates compared with results of series using larger diameters of beads.     

Fructose Containing Sugars Do Not Raise Blood Pressure or Uric Acid at Normal Levels of Human Consumption

The impact of fructose, commonly consumed with sugars by humans, on blood pressure and uric acid has yet to be defined. A total of 267 weight‐stable participants drank sugar‐sweetened milk every day for 10 weeks as part of their usual, mixed‐nutrient diet. Groups 1 and 2 had 9% estimated caloric intake from fructose or glucose, respectively, added to milk. Groups 3 and 4 had 18% of estimated caloric intake from high fructose corn syrup or sucrose, respectively, added to the milk. Blood pressure and uric acid were determined prior to and after the 10‐week intervention. There was no effect of sugar type on either blood pressure or uric acid (interaction P>.05), and a significant time effect for blood pressure was noted (P<.05). The authors conclude that 10 weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with fructose‐glucose–containing sugars, does not promote hyperuricemia or increase blood pressure.     

Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.     

Barriers to Screening and Possibilities for Active Detection of Family Medicine Attendees Exposed to Intimate Partner Violence

Introduction

In 1996 the World Health Organization declared intimate partner violence (IPV) the most important public health problem. Meta-analyses in 2013 showed every third female globally had been a victim of violence. Experts find screening controversial; family medicine is the preferred environment for identifying victims of violence, but barriers on both sides prevent patients from discussing it with doctors.

Methods

In July 2014, a qualitative study was performed through semi-structured interviews with ten family doctors of different ages and gender, working in rural or urban environments. Sound recordings of the interviews were transcribed, and the record verified. The data were interpreted using content analysis. A coding scheme was developed and later verified and analysed by two independent researchers. The text of the interviews was analysed according to the coding scheme.

Results

Two coding schemes were developed: one for screening, and the other for the active detection of IPV. The main themes emerging as barriers to screening were lack of time, staff turnover, inadequate finance, ignorance of a clear definition, poor commitment to screening, obligatory follow-up, risk of deterioration of the doctor-patient relationship, and insincerity on the part of the patient. Additionally, cultural aspects of violence, uncertainty/ helplessness, fear, lack of competence and qualifications, autonomy/negative experience, and passive role/stigma/ fear on the part of the patients were barriers to active detection.

Conclusion

All the participating doctors had had previous experience with active detection of IPV and were aware of its importance. Due to several barriers to screening for violence they preferred active detection.     

Dosimetry close to an 192Ir HDR source using N-vinylpyrrolidone based polymer gels and magnetic resonance imaging

In this work, the utilization of polymer gel-MRI dosimetry for measurements at distances relevant to clinical brachytherapy and intravascular applications [i.e., in the mm range, where steep three-dimensional (3-D) dose gradients exist] is investigated using N-vinylpyrrolidone-based gels. Transverse axis radial dose distributions, dose distributions parallel to the source axis, and 2-D dose distributions around the commonly used microSelectron 192Ir HDR source are measured for single source dwell position irradiations. Experimental results are found in good agreement with verified Monte Carlo calculations, even for distances less than 3 mm from the source. The effect of various MRI parameters, such as slice thickness, slice mispositioning, and in-plane resolution, on the accuracy of the method is also investigated. Possible limitations of the method are discussed, and its' overall potential in brachytherapy dosimetry is evaluated. Experimental 2-D dose distributions for an intravascular application following the Paris irradiation protocol are compared to corresponding commercial treatment planning system calculations. Results suggest that polymer gel-MRI dosimetry is capable of experimentally verifying dose distributions in relevant clinical intravascular applications.