Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity

BACKGROUND: This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. METHODS: The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm(3), daily EMF treatments were started by placing the cage of mice within the EMF field. Treatment ranged from 10 to 20 milli-Tesla (mT) and was given for 3 to 80 minutes either once or twice a day for 12 days. Tumors were measured and volumes calculated each 3–4 days. RESULTS: Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective tumor growth suppressor. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization. CONCLUSION: It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy

Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study.

BACKGROUND: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. METHODS: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. FINDINGS: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. INTERPRETATION: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. FUNDING: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received

More questions than answers to the diagnosis and management of cauda equina syndrome—Authors’ reply

No abstract available

Impact of treatment policies on patient outcomes and resource utilization in acute cholecystitis in Japanese hospitals

BACKGROUND: Although currently available evidence predominantly recommends early laparoscopic cholecystectomy (LC) for the treatment of acute cholecystitis, this strategy has not been widely adopted in Japan. Herein, we describe a hospital-based study of patients with acute cholecystitis in 9 Japanese teaching hospitals in order to evaluate the impact of different institutional strategies in treating acute cholecystitis on overall patient outcomes and medical resource utilization. METHODS: From an administrative database and chart review, we identified 228 patients diagnosed with acute cholecystitis who underwent cholecystectomy between April 2001 and June 2003. In order to examine the relationship between hospitals' propensity to perform LC and patient outcomes and/or medical resource utilization, we divided the hospitals into three groups according to the observed to expected ratio of performing LC (LC propensity), and compared the postoperative complication rate, length of hospitalization (LOS), and medical charges. RESULTS: No hospital adopted the policy of early surgery, and the mean overall LOS among the subjects was 30.9 days. The use of laparoscopic surgery varied widely across the hospitals; the adjusted rates of LC to total cholecystectomies ranged from 9.5% to 77%. Although intra-operative complication rate was significantly higher among patients whom LC was initially attempted when compared to those whom OC was initially attempted (9.7% vs. 0%), there was no significant association between LC propensity and postoperative complication rates. Although the postoperative time to oral intake and postoperative LOS was significantly shorter in hospitals with high use of LC, the overall LOS did not differ among hospital groups with different LC propensities. Medical charges were not associated with LC propensity. CONCLUSION: Under the prevailing policy of delayed surgery, in terms of the postoperative complication rate and medical resource utilization, our study did not show the superiority of LC in treating acute cholecystitis patients. The timing of surgery and discharge was mainly determined by the institutional policy in Japan, rather than by the clinical course of the patient; however, considering the substantially less postoperative pain and shorter recovery time of LC compared to OC, LC should be actively applied for the treatment of acute cholecystitis. If the policy of early surgery were universally applied, the advantage of LC over OC may be more clearly demonstrated

Psychometric properties of a generic, patient-centred palliative care outcome measure of symptom burden for people with progressive long term neurological conditions

Background There is no standard palliative care outcome measure for people with progressive long term neurological conditions (LTNC). This study aims to determine the psychometric properties of a new 8-item palliative care outcome scale of symptom burden (IPOS Neuro-S8) in this population. Data and Methods Data were merged from a Phase II palliative care intervention study in multiple sclerosis (MS) and a longitudinal observational study in idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The IPOS Neuro-S8 was assessed for its data quality, score distribution, ceiling and floor effects, reliability, factor structure, convergent and discriminant validity, concurrent validity with generic (Palliative care Outcome Scale) and condition specific measures (Multiple Sclerosis Impact Scale; Non-motor Symptoms Questionnaire; Parkinson's Disease Questionnaire), responsiveness and minimally clinically important difference. Results Of the 134 participants, MS patients had a mean Extended Disability Status Scale score 7.8 (SD = 1.0), patients with an IPD, MSA or PSP were in Hoehn & Yahr stage 3±5. The IPOS Neuro-S8 had high data quality (2% missing), mean score 8 (SD = 5; range 0±32), no ceiling effects, borderline floor effects, good internal consistency (Cronbach's α = 0.7) and moderate test-retest reliability (intraclass coefficient = 0.6). The results supported a moderately correlated two-factor structure (Pearson's r = 0.5). It was moderately correlated with generic and condition specific measures (Pearson's r: 0.5±0.6). There was some evidence for discriminant validity in IPD, MSA and PSP (p = 0.020), and for good responsiveness and longitudinal construct validity. Conclusions IPOS Neuro-S8 shows acceptable to promising psychometric properties in common forms of progressive LTNCs. Future work needs to confirm these findings with larger samples and its usefulness in wider disease groups

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion

What is the empirical evidence that hospitals with higher-risk adjusted mortality rates provide poorer quality care? A systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Despite increasing interest and publication of risk-adjusted hospital mortality rates, the relationship with underlying quality of care remains unclear. We undertook a systematic review to ascertain the extent to which variations in risk-adjusted mortality rates were associated with differences in quality of care.</p> <p>Methods</p> <p>We identified studies in which risk-adjusted mortality and quality of care had been reported in more than one hospital. We adopted an iterative search strategy using three databases – Medline, HealthSTAR and CINAHL from 1966, 1975 and 1982 respectively. We identified potentially relevant studies on the basis of the title or abstract. We obtained these papers and included those which met our inclusion criteria.</p> <p>Results</p> <p>From an initial yield of 6,456 papers, 36 studies met the inclusion criteria. Several of these studies considered more than one process-versus-risk-adjusted mortality relationship. In total we found 51 such relationships in a widen range of clinical conditions using a variety of methods. A positive correlation between better quality of care and risk-adjusted mortality was found in under half the relationships (26/51 51%) but the remainder showed no correlation (16/51 31%) or a paradoxical correlation (9/51 18%).</p> <p>Conclusion</p> <p>The general notion that hospitals with higher risk-adjusted mortality have poorer quality of care is neither consistent nor reliable.</p

Complement C3d Conjugation to Anthrax Protective Antigen Promotes a Rapid, Sustained, and Protective Antibody Response

B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA) to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax™) consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA) imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4) of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure

Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study

<p>Abstract</p> <p>Background</p> <p>The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1) improve nutrition, (2) increase health literacy and, (3) increase physical activity. This study is a response to this call to action.</p> <p>Methods</p> <p>After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1). Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2).</p> <p>Results</p> <p>There were no significant differences between the two groups in baseline bone mineral density (BMD) or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass). In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition.</p> <p>Both groups experienced a significant positive mean annualized percent change (MAPC) in BMD compared to expectation [AlgaeCal 1: 1.15%, <it>p </it>= 0.001; AlgaeCal 2: 2.79%, <it>p </it>= 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, <it>p </it>= 0.14; AlgaeCal 2: 2.18%, <it>p </it>< 0.001]. The MAPC in AlgaeCal 2 was significantly greater than that in AlgaeCal 1 (<it>p </it>= 0.005). The MAPC contrast between compliant and partially compliant subjects was significant for both plans (<it>p </it>= 0.001 and <it>p </it>= 0.003 respectively). No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group.</p> <p>Conclusions</p> <p>Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from baseline was significantly greater than the increase from baseline in AlgaeCal 1. Increased compliance was associated with greater increases in BMD in both groups. No adverse effects were reported in either group.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01114685">NCT01114685</a></p