Stem cell bioengineering strategies to widen the therapeutic applications of haematopoietic stem/progenitor cells from umbilical cord blood

Umbilical cord blood (UCB) transplantation has observed a significant increase in recent years, due to the unique features of UCB haematopoietic stem/progenitor cells (HSCs) for the treatment of blood‐related disorders. However, the low cell numbers available per UCB unit significantly impairs the widespread use of this source for transplantation of adult patients, resulting in graft failure, delayed engraftment and delayed immune reconstitution. In order to overcome this issue, distinct approaches are now being considered in clinical trials, such as double‐UCB transplantation, intrabone injection or ex vivo expansion. In this article the authors review the current state of the art, future trends and challenges on the ex vivo expansion of UCB HSCs, focusing on culture parameters affecting the yield and quality of the expanded HSC grafts: novel HSC selection schemes prior to cell culture, cytokine/growth factor cocktails, the impact of biochemical factors (e.g. O₂) or the addition of supportive cells, e.g. mesenchymal stem/stromal cell (MSC)‐based feeder layers) were addressed. Importantly, a critical challenge in cellular therapy is still the scalability, reproducibility and control of the expansion process, in order to meet the clinical requirements for therapeutic applications. Efficient design of bioreactor systems and operation modes are now the focus of many bioengineers, integrating the increasing 'know‐how' on HSC biology and physiology, while complying with the GMP standards for the production of cellular products, i.e. through the use of commercially available, highly controlled, disposable technologies. Copyright © 2013 John Wiley & Sons, Ltd.     

Mother-to-Child Transmission of Chagas Disease in El Salvador

To estimate the incidence (any mother to child) and rate (from seropositive mother to child) of mother-to-child transmission of Trypanosoma cruzi, a serological census was conducted, targeting pregnant women and infants born to seropositive mothers, in four municipalities of El Salvador. Of 943 pregnant women, 36 (3.8%) were seropositive for T. cruzi. Of 36, 32 proceeded to serological tests of their infants when they became 6–8 months of age. Six infants seropositive at the age of 6–8 months further proceeded to second-stage serological test at the age of 9–16 months. As the result, one infant was congenitally infected. Thus, serological tests at the age of 6–8 months produced five false positives. To ensure earlier effective medication only for true positives, identification of seropositive infants at the age of 9–16 months is crucial. Incidence and rate of mother-to-child transmission were 0.14 (per 100 person-years) and 4.0%, respectively. Estimated number of children infected through mother-to-child transmission in El Salvador (170 per year) was much higher than that of human immunodeficiency virus (HIV; seven per year). It is recommended that serological testing for T. cruzi be integrated into those for HIV and syphilis as part of antenatal care package.     

Effect of Two Types of Active Recovery on Fatigue and Climbing Performance

Performing intra-session recovery is important in rock climbing due to the multiple efforts that climbers are required to make in competitions, as well as repeated climbing trials that they carry out during training sessions. Active recovery has been shown to be a better option than passive recovery. However, the type of active recovery that should be done and the influence of the type and quantity of muscle mass activated are not clear. The aim of this study was to compare the effects of recovering with easy climbing (CR) or walking (WR) on markers of fatigue and climbing performance. For this purpose, 14 subjects participated in this randomly assigned crossover protocol completing three two-minute climbing trials separated by two minutes of active recovery with the assigned method. Seven days later participants carried out the same protocol with the other recovery method. Blood lactate (La^-), rating of perceived exertion (RPE), and heart rate (HR) were analyzed as markers of fatigue and recovery, while meters climbed (MC) and handgrip force (HF) were analyzed for performance. La- values before the last climbing trial (p < 0.05; d = 0.69) and Peak La- values (p < 0.05; d = 0.77) were lower for CR than for WR. Climbers were able to ascend more meters in the set time when following the CR protocol (p < 0.01; d = 0.6), which shows the important role of the active recovery method carried out on climbing performance. There were no differences in HR, HF or RPE between protocols. A more sport-specific recovery protocol, in addition to moving great muscle mass (e.g. lower limbs), seems to enhance recovery and to facilitate lactate removal. For this reason, CR appears to be a more effective active recovery method than WR in sport rock climbing.

Key points

• Climbing recovery improved lactate removal in comparison with walking recovery.
• Subjects were able to climb more meters in a determined time when easy climbing instead of walking during recoveries.
• Activating both great muscle mass like that of the lower limbs as well as the main fatigue producing muscles (forearms in climbing) seems more effective for recovering than activating just great muscle mass.

Key words: Blood lactate, rock climbing, handgrip force, active recovery, fatigue, performance     

Retrograde Headless Intramedullary Screw Fixation for Displaced Fifth Metacarpal Neck and Shaft Fractures: Short Term Results

BackgroundThis study aimed to evaluate the early clinical outcomes of retrograde headless intramedullary screw fixation for displaced fifth metacarpal neck and shaft fractures.MethodsWe retrospectively reviewed nine patients treated with retrograde intramedullary screw fixation of fifth metacarpal neck and shaft fractures between 2011 and 2013. Patient demographics and outcomes including hand dominance, age, sex, type of injury, injury and postoperative radiographs, return to work, time to fracture union radiographically, complications, visual analog score, disabilities of the arm, shoulder, and hand scores, postoperative metacarpophalangeal joint range of motion, and grip strength were recorded.ResultsNine fractures in nine patients with a mean age of 32 years (19–54) were included. There were seven metacarpal neck and two metacarpal shaft fractures. All patients sustained injury by direct impact of fist against an object. No case involved worker’s compensation. Patients had a mean follow-up of 36 weeks (6–57 weeks) and at the time of latest follow-up had no pain. Mean radiographic healing was 49 days (28–85 days). Mean return to work was 6 weeks (4–10 weeks). Mean metacarpalphalangeal joint motion was 0° extension and 90° flexion. Mean disabilities of the arm, shoulder, and hand scores pre- and postoperatively improved from 43 to 0.7, respectively. The mean postoperative grip strength was measured of the injured hand (40 kg) and un-injured hand (41 kg).ConclusionsRetrograde headless intramedullary screw fixation of fifth metacarpal neck and shaft fractures has overall favorable early outcomes and offers the benefit of stable fixation, early motion without cast immobilization, and the ability for early return to work. This technique is a viable surgical option for these fractures and may be considered in the appropriate patient population.     

Analysis of monotherapy prostate brachytherapy in patients with prostate cancer. Initial PSA and Gleason are important for recurrence?

Purpose

To evaluate the clinical outcome of a cohort of localized prostate cancer patients treate with 125-I permanent brachytherapy at the São José Hospital – CHLC, Lisbon.

Materials and Methods

A retrospective analysis was carried out on 429 patients with low and intermediate-risk of prostate adenocarcinoma, according to the recommendations of the EORTC, who underwent 125I brachytherapies in intraoperative dosimetry “real-time” system between September 2003 and September 2013.

Results

The mean follow-up was 71.98 months. Biochemical relapse of disease by rising PSA (Phoenix criterion) was observed in 18 patients (4.2%). Through the application of Kaplan-Meier survival curves in this sample, the rate of survival at 6 years without biochemical relapse was higher than 95%. By Iog rank test comparing biochemical relapse with initial PSA (15-10 and <10) and Gleason values (7 and <7), there was no statistical difference (P=0.830) of the initial PSA in the probability of developing biochemical relapse. In relation to Gleason score, it was noted a statistical difference (P<0.05), demonstrating that patients with Gleason 7 are more likely to develop biochemical relapse.

Conclusions

Brachytherapy as monotherapy is at present an effective choice in the treatment of localized prostate adenocarcinoma. Biochemical relapses are minimal. The initial PSA showed no statistically difference in the rate of relapses, unlike the value Gleason, where it was demonstrated that patients with Gleason 7 have a higher probability of biochemical relapse. Cases with PSA bounce should be controlled before starting a salvage treatment.