Digital droplet PCR-based absolute quantification of pre-transplant <Emphasis Type="Italic">NPM1</Emphasis> mutation burden predicts relapse in acute myeloid leukemia patients

Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable (“minimal”) residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves. Using ddPCR, we analyzed pre-transplant peripheral blood and bone marrow of 51 NPM1-mutated acute myeloid leukemia patients transplanted in complete remission or complete remission with incomplete recovery. Mutated NPM1 measurable residual disease-positive patients had higher cumulative incidence of relapse (P?<?0.001) and shorter overall survival (P?=?0.014). Restricting the analyses to patients receiving non-myeloablative conditioning, mutated NPM1 measurable residual disease positivity is associated with higher cumulative incidence of relapse (P?<?0.001) and shorter overall survival (P?=?0.006). Positive mutated NPM1 measurable residual disease status determined by ddPCR before allogeneic stem cell transplantation is associated with worse prognosis independent of other known prognostic markers—also for those receiving non-myeloablative conditioning. In the future, mutated NPM1 measurable residual disease status determined by ddPCR might guide treatment and improve patients’ outcomes.     

Exploring Perceived Barriers and Facilitators of PrEP Uptake among Young People in Uganda,Zimbabwe, and South Africa

Archives of Sexual Behavior - Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. Few studies have explored adolescents and young people’s perspectives toward PrEP. We...     

Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications

Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible ‘killer-application’ for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.     

An update on radiation therapy in head and neck cancers

Introduction: Technological and technical improvements allowed for significant advances in the field of radiation therapy (RT) of head and neck cancer (HNC). Several organ-sparing strategies have been investigated with the objective to decrease acute and long-term adverse effects and, subsequently, to assure a better quality of life in patients affected by HNC. In this context, intensity modulated irradiation and the use of multimodality-imaging could help clinicians to obtain a rapid dose fall off towards surrounding healthy tissues and a better delineation of targets volumes and organs at risk.

Areas covered: A literature review was performed with the aim to offer an update on radiation therapy in HNC.

Expert commentary: During these last years, radiation oncologists have observed a continuous changing regarding radiation treatment for HNC. The adoption of intensity-modulated RT (IMRT) and the use of multimodality-imaging for tumor volume definition and organs at risk or delineation have improved the clinical outcomes of HNC patients. In the future, a better integration of functional imaging for target volume delineation as well as adaptive delivery strategies will allow to further personalize radiation oncology in HNC. Furthermore, the latest breakthrough technologies, such as magnetic resonance imaging (MRI)-linacs and heavy particles technologies have a great potential to improve treatment-related quality of life in HNC. Future studies are needed to demonstrate the clinical advantages of these new RT technologies in HNC.     

URINARY NO3− EXCRETION AS AN INDICATOR OF NITRIC OXIDE FORMATION IN VIVO DURING ORAL ADMINISTRATION OF l-ARGININE OR l-NAME IN RATS

• 1 Endothelium-derived nitric oxide (NO), a major modulator of vascular tone, is synthesized from the terminal guanidino nitrogen of l -arginine. This reaction is inhibited by analogues of l -arginine, such as N-nitro-l -arginine methyl ester (l -NAME). Many of the biological effects of NO are mediated by the second messenger cGMP. NO is rapidly oxidized to NO₃^? which, like cGMP, is eliminated via excretion into the urine. In a placebo controlled study, we investigated whether oral bolus administration of l -arginine and l -NAME affects the urinary excretion rates of NO₃^? and cGMP in Munich Wistar Frömmter (MWF) rats.
• 2 Twenty MWF rats were kept in metabolic cages and received l -arginine (3 g/kg body weight), l -NAME (50mg/kg), or placebo (0.9% saline) in randomized order. Urine samples were sequentially collected for 10 h and analysed for creatinine, NO₃^? and cGMP.
• 3 l -Arginine induced a slight, but prolonged increase in urine flow, whereas l -NAME induced an early, transient increase in urine flow which was followed by a decrease. Creatinine clearance decreased by 65% after l -NAME, but was not affected by l -arginine or placebo.
• 4 Urinary NO₃^? and cGMP excretion rates transiently increased after l -arginine (NO₃^?: + 29%; cGMP: + 16%) for 4–5h, whereas l -NAME induced an immediate, pronounced and lasting inhibition of urinary NO₃^? and cGMP excretion (NO₃^?:-76%; cGMP:-46%). Urinary NO₃^? and cGMP excretions were significantly correlated (r = 0.755; P< 0.001).
• 5 Urinary excretion rates of NO₃^? and cGMP, expressed as μmol/h, were correlated to urine flow (mL/h; r = 0.617 and 0.649, respectively; both P<0.05), whereas after correction by urinary creatinine (μmol/mmol creatinine) no correlation with urine flow was observed, indicating that these excretion rates were independent of renal excretory function. Thus we conclude that changes in the urinary excretion rates of NO₃^? and cGMP represent changes in NO production rates in vivo when expressed in relation to urinary creatinine. Urinary NO₃^? and cGMP excretion is modulated by acute NO synthase inhibition or substrate provision.

     

The Cortisol Awakening Response and Depressive Symptomatology: The Moderating Role of Sleep and Gender

The association between depression and the cortisol awakening response (CAR) has been widely examined, yet the results are mixed and factors responsible for such inconsistencies are poorly understood. The current study investigated whether the link between depressive symptomatology and CAR varied as a function of two such factors: sleep and gender. The sample included 58 young adults (30 females; M_age = 18.7; SD_age = 0.91). Participants completed the Beck Depression Inventory as well as the Consensus Sleep Diary to assess depressive symptomatology and daily sleep patterns, respectively. Participants also provided four salivary cortisol samples (0, 30, 45 and 60 min after awakening) during two consecutive weekdays. Results demonstrated that greater depressive symptoms were associated with a greater CAR but only when depressive symptoms were linked to a shorter sleep time. In addition, gender significantly moderated the association between depressive symptoms and CAR. While greater depressive symptoms were associated with an elevated CAR among females, they were associated with a blunted CAR among males. These findings provide some insight into potential mechanisms linking depressive symptomatology and CAR, and suggest that future studies examining CAR as a biomarker of depression should account for differences in sleep and gender. Copyright © 2016 John Wiley & Sons, Ltd.     

Functional Medium-Term Results After Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus: A 5-Year Prospective Cohort Study

Autologous matrix-induced chondrogenesis (AMIC) has gained popularity in the treatment of osteochondral lesions of the talus. Previous studies have presented promising short-term results for AMIC talar osteochondral lesion repair, a 1-step technique using a collagen type I/III bilayer matrix. The aim of the present study was to investigate the mid-term effects. The 5-year results of a prospective cohort study are presented. All patients underwent an open AMIC procedure for a talar osteochondral lesion. Data analysis included general demographic data, preoperative magnetic resonance imaging findings, intraoperative details, and German version of the Foot Function Index (FFI-D) scores preoperatively and at 1 and 5 years after surgery. The primary outcome variable was the longitudinal effect of the procedure, and the influence of various variables on the outcome was tested. Of 47 consecutive patients, 21 (45%) were included. Of the 21 patients, 8 were female (38%) and 13 were male (62%), with a mean age of 37 ± 15 (range 15 to 62) years and a body mass index of 26 ± 5 (range 20 to 38) kg/m². The defect size was 1.4 ± 0.9 (range 0.2 to 4.0) cm². The FFI-D decreased significantly from preoperatively to 1 year postoperatively (56 ± 18 versus 33 ± 25; p = .003), with a further, nonsignificant decrease between the 1- and 5-year follow-up examination (33 ± 25 versus 24 ± 21; p = .457). Similar results were found for the FFI-D subscales of function and pain. The body mass index and lesion size showed a positive correlation with the preoperative FFI-D overall and subscale scores. These results showed a significant improvement in pain and function after the AMIC procedure, with a significant return to sports by the 5-year follow-up point. The greatest improvement overall was seen within the first year; however, further clinical satisfaction among the patients was noticeable after 5 years.