Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells

High-dose therapy with autologous marrow or peripheral blood stem cell (PBSC) rescue has been extensively applied in the treatment of multiple myeloma (MM) patients during the past 10 years resulting in improved event-free and overall survival when compared with standard chemotherapy. However, relapses are common and cure is unlikely in the majority of patients. Because both bone marrow and PBSCs are contaminated with myeloma cells it is conceivable that relapse after autotransplantation originates at least in part from autografted tumor cells. In this study, mobilized PBSCs were examined for the presence of myeloma cells based on immunophenotyping and sensitive polymerase chain reaction (PCR)-based techniques. In addition, CD34+ Lin- Thy+ stem cells were purified from mobilized PBSC harvests of 10 MM patients by sequentially using counterflow elutriation centrifugation, treatment with phenylalanine methylester, and flow sorting, using 5-parameter gating (propidium iodide, forward scatter, side scatter, CD34+ v Lin- and CD34+ v Thy+). Virtually all mobilized unsorted PBSC preparations contained myeloma cells in sufficient quantities (range, < 0.01 to > 10%) potentially causing a disease relapse. Stem cell purification led to an overall enrichment by about 50-fold in all 10 patients; approximately 90% of the final cell population expressed CD34+ Lin- Thy+ with no evidence of myeloma cell contamination based on flow cytometric analysis of CD38bright cells (< 0.1%). Quantitative PCR amplification of patient-specific complementarity determining region III (CDRIII) DNA sequences showed depletion of clonal B cells by 2.7 to 7.3 logs, with the highest log reduction noted in the samples initially containing the most tumor cells. Our results show that purification of CD34+ Lin- Thy+ cells depletes myeloma cells to undetectable levels from up to 10% present in unsorted PBSCs, thus offering a tool to investigate whether MM relapse after autotransplantation can be reduced markedly.     

The relationship between smartphone use and subjective musculoskeletal symptoms and university students

[Purpose] The purpose of this study was to investigate the use of smartphones by university students in selected areas, their musculoskeletal symptoms, and the associated hazard ratio. [Subjects and Methods] This involved the completion of a self-administered questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The 292 completed copies of the questionnaire were then analyzed. [Results] The most painful body regions after the use of smartphones were found to be the shoulders and neck. In the musculoskeletal system, back pain was found to have a positive correlation with the size of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were found to have a negative correlation with the length of time that the smartphone was used. As a result, it was revealed that the use of a smartphone was correlated with musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of smartphones is on the rise, it is necessary to improve the ways that they are used and to develop a preventive program to alleviate the symptoms of musculoskeletal damage.Key words: Smartphone, Musculoskeletal symptoms, Prevent     

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.     

Effect of Omega-3 Fatty Acids on Kidney Function after Myocardial Infarction: The Alpha Omega Trial

Background and objectives

Kidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.

Design, setting, participants, & measurements

In the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60–80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid–docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine–cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.

Results

Patients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine–cystatin C-based GFR was −6.9 (±12.6), −4.8 (±13.4), −6.2 (±12.8), and −6.0 (±13.0) ml/min per 1.73 m² in the placebo, eicosapentaenoic acid–docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid–docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid–docosahexaenoic acid compared with placebo, the decline in creatinine–cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m²; other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m²) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid–docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.

Conclusions

Long-term supplementation with 400 mg/d eicosapentaenoic acid–docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.     

An open multicentre pilot study examining the safety,efficacy and tolerability of fast titrated (800 mg/day by day 4) quetiapine in the treatment of schizophrenia/schizoaffective disorder

Objective. Rapid dose escalation of quetiapine could offer prompt and effective therapy to patients requiring hospitalization for schizophrenia or schizoaffective disorder. This study evaluated the safety, tolerability, and efficacy of a rapid dose escalation of quetiapine to 800 mg/day over 4 days in patients with severe psychotic symptoms diagnosed as schizophrenia or schizoaffective disorder. Methods. In this open-label, multicenter, pilot study, 14 patients aged 18 years or older, requiring hospitalization for schizophrenia or schizoaffective disorder, received quetiapine orally twice daily for 14 days. Quetiapine was administered according to the schedule: 200, 400, 600, and 800 mg/day on the first four treatment days, followed by flexible dosing within the range 400–800 mg/day during the next 10 days. The primary endpoint was to evaluate the safety and tolerability of a fast titration of quetiapine (200, 400, 600, 800 mg/day on the first four treatment days). Effectiveness of a fast titration of quetiapine was the secondary objective of this investigation. Efficacy assessments in the intent-to-treat (ITT) population included changes in the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity of Illness (CGI-S) scores from Day 1 (baseline) to Day 14. Results. In 4 days 14 patients were titrated up to a dose of 800 mg/day. Ten patients were diagnosed with schizophrenia, one subject was suffering from schizoaffective disorder of the depressive type and three patients were diagnosed with schizoaffective disorder of the bipolar type. Eleven patients (79%) completed the study. Two patients discontinued the trial because of non-compliance and one patient because of a prolonged QTcB interval. Overall, 29 AEs were reported during this trial, all were considered mild or moderate in severity. During the first 7 days of the trial, 25 AEs were reported in 11 patients. The majority of AEs were considered as possibly related to the study medication. No deaths or serious adverse events were reported. Physical examination at the last trial visit revealed no clinically relevant changes versus baseline and there were no consistent changes over time in vital signs. The BARS and SAS scores indicated an improvement of EPS during the study. After 4 days of fast titration, the mean total PANSS score decreased from 92.8 at baseline to a value of 87.4, there was a further decrease to 78.2 at endpoint. This corresponds to a statistically significant decrease by 14.6 versus baseline (P<0.01). After 4 days of fast titration, the mean CGI-S score was improved from 4.7 at baseline to a value of 4.3 and improved further to 3.8 at endpoint, corresponding to a statistically significant decrease of 0.9 points versus baseline (P<0.01). Conclusion. In this study, fast titration of quetiapine to 800 mg/day over 4 days was generally well tolerated and effective in reducing psychotic symptoms in patients requiring hospitalization for schizophrenia/schizoaffective disorder.     

The diagnostic value of fine needle aspiration in parotid lumps

Introduction

Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.

Methods

A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.

Results

In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.

Conclusions

FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.     

Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists

AIMS: To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between non-expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand. METHODS AND RESULTS: In this prospective multicentre study, non-expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by kappa statistics. Due to absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia/low-grade dysplasia (IND/LGD) versus high-grade dysplasia (HGD)/adenocarcinoma (AC)] between non-experts and first panel experts and between initial experts and first panel experts was fair (kappa = 0.24 and kappa = 0.27, respectively), and substantial for differentiation of HGD/AC from ND/IND/LGD (kappa = 0.62 and kappa = 0.58, respectively). CONCLUSIONS: There was considerable interobserver variability in the interpretation of ND or IND/LGD in BO between non-experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.