Laparoscopy versus laparotomy for benign ovarian tumours (Review)

Background: Over the last ten years laparoscopy and minilaparotomy have become increasingly common approaches for the surgical removal of benign ovarian tumours. However in the event that a tumour is found to be malignant, laparotomy is the appropriate procedure. Careful preoperative assessment including transvaginal ultrasound with morphological scoring, colour doppler assessment of vascular quality and a serum Ca125 level is desirable. Objectives: To determine the benefits, harms and cost of laparoscopy or minilaparotomy compared with laparotomy in women with benign ovarian tumours. Search strategy: We searched electronic databases, trials registers and reference lists of published trial reports. Reference lists from trials and review articles were also searched. Selection criteria: All randomised controlled trials comparing either laparoscopy or minilaparotomy with laparotomy for benign ovarian tumours. Data collection and analysis: Eight reviewers independently assessed the eligibility and quality of each study, and independently extracted the data Main results The results of nine randomised controlled trials (n=482 women) showed that laparoscopic surgery was associated with fewer adverse events of surgery (surgical injury or post operative complications including fever or infection) (OR 0.3 95% CI 0.2 to 0.5), less post operative pain (VAS scores WMD -2.4 95% CI -2.7 to -2.0), greater likelihood of being pain free after 2 days (OR 7.42 95% CI 4.86 to 11.33) and fewer days in hospital (WMD -2.88 95%CI -3.1 to -2.7) . In one study that reported costs, laparoscopy was associated with a significant reduction compared to laparotomy(WMD - $1045 95$1348 to -$742) in US$ in 1993. Very high levels of heterogeneity made it inappropriate to pool data on duration of surgery. Three RCT’s compared laparoscopy versus minilaparotomy and found that laparoscopy was associated with reduced odds of any adverse event (surgical injury or postoperative complications ) (OR 0.10 95% CI 0 to 0.8) lower VAS scores for pain (WMD -1.0 95%CI -1.6 to -0.45). Duration of hospital stay ranged between 1 and 2.2 days with substantial heterogeneity. Authors’ conclusions In women undergoing surgery for benign ovarian tumours, laparoscopy was associated with a reduction in fever, urinary tract infection, post operative complications, post operative pain, number of days in the hospital and total cost. These findings should be interpreted with caution since only a small number of studies were identified including a total of only 769 women and not all of the important outcomes were reported in each study

Laparoscopy versus laparotomy for benign ovarian tumour

Background: Over the last 10 years laparoscopy and minilaparotomy have become increasingly common approaches for the surgical removal of benign ovarian tumours. However, in the event that a tumour is found to be malignant, laparotomy is the appropriate procedure. Careful preoperative assessment including transvaginal ultrasound with morphological scoring, colour doppler assessment of vascular quality, and serum cancer antigen 125 (CA 125) level is desirable. Objectives: To determine the benefits, harms, and cost of laparoscopy orminilaparotomy compared with laparotomy in women with benign ovarian tumours. Search methods: We searched electronic databases, trial registers, and reference lists of published trial reports. Reference lists from trials and review articles were searched. Selection criteria: All randomised controlled trials comparing either laparoscopy or minilaparotomy with laparotomy for benign ovarian tumours. Data collection and analysis: Eight review authors independently assessed the eligibility and quality of each study and extracted the data Main results: The results of nine randomised controlled trials (N = 482 women) showed that laparoscopic surgery was associated with fewer adverse events of surgery (surgical injury or postoperative complications including fever or infection) (OR 0.3, 95% CI 0.2 to 0.5), less postoperative pain (VAS score WMD -2.4, 95% CI -2.7 to -2.0), greater likelihood of being pain free after two days (OR 7.42, 95% CI 4.86 to 11.33), and fewer days in hospital (WMD -2.88, 95% CI -3.1 to -2.7) than with laparotomy. In one study that reported costs, laparoscopy was associated with a significant reduction in costs compared to laparotomy (WMD - USD 1045, 95% CI -1348 to -742) in 1993. Very high levels of heterogeneity made it inappropriate to pool data on duration of surgery. Three RCTs compared laparoscopy versus minilaparotomy and found that laparoscopy was associated with reduced odds of any adverse event (surgical injury or postoperative complications) (OR 0.10, 95% CI 0 to 0.8) and lower VAS scores for pain (WMD -1.0, 95% CI -1.6 to -0.45). Duration of hospital stay ranged between 1 and 2.2 days, with substantial heterogeneity. Authors’ conclusions: In women undergoing surgery for benign ovarian tumours, laparoscopy was associated with a reduction in fever, urinary tract infection, postoperative complications, postoperative pain, number of days in hospital, and total cost. These findings should be interpreted with caution since only a small number of studies were identified. These included a total of only 769 women and not all of the important outcomes were reported in each study

The CCAAT displacement protein/cut homeodomain protein represses osteocalcin gene transcription and forms complexes with the retinoblastoma protein-related protein p107 and cyclin A

Developmental control of bone tissue-specific genes requires positive and negative regulatory factors to accommodate physiological requirements for the expression or suppression of the encoded proteins. Osteocalcin (OC) gene transcription is restricted to the late stages of osteoblast differentiation. OC gene expression is suppressed in nonosseous cells and osteoprogenitor cells and during the early proliferative stages of bone cell differentiation. The rat OC promoter contains a homeodomain recognition motif within a highly conserved multipartite promoter element (OC box I) that contributes to tissue-specific transcription. In this study, we demonstrate that the CCAAT displacement protein (CDP), a transcription factor related to the cut homeodomain protein in Drosophila melanogaster, may regulate bone-specific gene transcription in immature proliferating osteoblasts. Using gel shift competition assays and DNase I footprinting, we show that CDP/cut recognizes two promoter elements (TATA and OC box I) of the bone-related rat OC gene. Overexpression of CDP/cut in ROS 17/2.8 osteosarcoma cells results in repression of OC promoter activity; this repression is abrogated by mutating OC box I. Gel shift immunoassays show that CDP/cut forms a proliferation-specific protein/DNA complex in conjunction with cyclin A and p107, a member of the retinoblastoma protein family of tumor suppressors. Our findings suggest that CDP/cut may represent an important component of a cell signaling mechanism that provides cross-talk between developmental and cell cycle-related transcriptional regulators to suppress bone tissue-specific genes during proliferative stages of osteoblast differentiation

BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network

Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2. However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis. Here we show that BMP2 induces DLX3, a homeodomain protein that activates Runx2 gene transcription. Small interfering RNA knockdown studies in osteoblasts validate that DLX3 is a potent regulator of Runx2. Furthermore in Runx2 null cells, DLX3 forced expression suffices to induce transcription of Runx2, osteocalcin, and alkaline phosphatase genes, thus defining DLX3 as an osteogenic regulator independent of RUNX2. Our studies further show regulation of the Runx2 gene by several homeodomain proteins: MSX2 and CDP/cut repress whereas DLX3 and DLX5 activate endogenous Runx2 expression and promoter activity in non-osseous cells and osteoblasts. These HD proteins exhibit distinct temporal expression profiles during osteoblast differentiation as well as selective association with Runx2 chromatin that is related to Runx2 transcriptional activity and recruitment of RNA polymerase II. Runx2 promoter mutagenesis shows that multiple HD elements control expression of Runx2 in relation to the stages of osteoblast maturation. Our studies establish mechanisms for commitment to the osteogenic lineage directly through BMP2 induction of HD proteins DLX3 and DLX5 that activate Runx2, thus delineating a transcriptional regulatory pathway mediating osteoblast differentiation. We propose that the three homeodomain proteins MSX2, DLX3, and DLX5 provide a key series of molecular switches that regulate expression of Runx2 throughout bone formation. <br/

Restorative treatment decisions for carious lesions: Do Russian dentists and dental students apply minimal intervention dentistry?

Background - The concept of minimal intervention dentistry (MID) includes both delayed restorative treatment and conservative caries removal, and is now recognised as an evidence-based approach for dental caries management. In order to determine if dental professionals in Russia are incorporating this concept into their clinical practice, we investigated the restorative treatment decisions of Russian dentists and dental students, and the factors associated with these decisions. Methods - We included 171 general dental practitioners and dental therapists (collectively referred to here as “dentists”) from North-West Russia, and 76 dental undergraduate students from the Northern State Medical University in Arkhangelsk (response rate of 11.5% and 67.9%, respectively). Participants completed a questionnaire, which collected background information (sex, region of work, place of dental school graduation, practice type, years of working experience, working in an urban or rural area, and specialisation in restorative dentistry) and information on restorative treatment decisions for proximal and occlusal carious lesions of permanent teeth. Treatment options in accordance with MID were defined as intervention at dentin level and minimally invasive cavity preparation. Multinomial logistic regression was used for statistical analysis. Results - For the proximal carious lesion, 9.4% of participants said they would employ both MID treatment options; 60.7% said they would choose only one; and 29.9% said they would use neither option. For the occlusal carious lesion, the corresponding figures were 37.2%, 52.1%, and 10.7%. No differences in restorative treatment options were observed among general dental practitioners, dental therapists, and dental students. For the proximal carious lesion, dentists from regions outside Arkhangelsk had 4.15 (95% confidence interval [CI] 1.13–15.27) times higher odds of following one versus both MID treatment options. For the occlusal carious lesion, working experience above 15 years was associated with higher odds of using only one versus both MID treatment options (adjusted odds ratio = 3.04, 95% CI 1.33–6.91). Almost all respondents preferred tooth-coloured materials for restorations; more than 75% chose resin-based composite. Conclusions - The majority of Russian dentists and dental students do not apply the MID concept when treating dental caries in permanent teeth. Clinical protocols on dental caries treatment and dental school curriculums should be updated to place an enhanced focus on evidence-based practice and preventive strategies. Further studies with larger samples of Russian dentists and dental students and alternative methods of recruitment are needed to validate our results

Commercializing Biomedical Research Through Securitization Techniques

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors

Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Sensitivity of intermediate mass fragment flows to the symmetry energy

The NIMROD-ISiS array was used to study the transverse flow of intermediate mass fragments in 35 MeV/nucleon ${}^{70}\mathrm{Zn}+{}^{70}\mathrm{Zn}$, ${}^{64}\mathrm{Zn}+{}^{64}\mathrm{Zn}$, and ${}^{64}\mathrm{Ni}+{}^{64}\mathrm{Ni}$ reactions. The intermediate mass fragment flow was previously shown to be sensitive to the density dependence of the symmetry energy. To explore the model dependence of the results, the antisymmetrized molecular dynamics, constrained molecular dynamics, and stochastic mean-field models were each compared to the experimental results to extract information on the form of the symmetry energy. The results demonstrate that sensitivity of the models to the nuclear equation of state can vary significantly based on the treatment of the nuclear dynamics. Despite the differences in the sensitivity, improved agreement with the experimental data is observed for each model with a stiff density dependence of the symmetry energy

A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs