Outcomes of enhanced recovery after surgery (ERAS) in gynecologic oncology - A systematic review and meta-analysis.

OBJECTIVE: To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost. RESULTS: A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2-2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55-0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64-0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23-1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544). CONCLUSIONS: ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.

Checkpoint inhibitors: a cutting edge in oncology.

The checkpoint inhibitor field, and indeed the whole of immuno-oncology, is fast-paced and fascinating, with huge clinical and commercial potential. The challenge in the coming years will be to define the best type and combination of immunotherapy, and the best target population to receive it. Keytruda's ground-breaking approval for a biomarker-based rather than location-based indication is a solid step in this direction, and is likely to be followed by other such approvals. As the field develops, it is to be hoped that immuno-oncology therapeutics will continue to deliver the significant improvements in patient outcome that have been seen so far.

Microbial and nutrient pollution of coastal bathing waters in Mauritius.

The coastal pollution problem in Mauritius is exacerbated by the hydrogeology of the volcanic substratum. Bacterial contamination of bathing waters and nutrients, water temperature, salinity, and dissolved oxygen (DO) were monitored at three different spatial and temporal scales along the coastline of Mauritius during 1997-1998. Standard techniques for water sample collection and analysis set by the American Public Health Association [APHA. Standard methods for the examination of water and wastewater. 19th ed. Washington, DC: APHA, 1995.] were used at: (a) 16 sites around the island over a period of 7 months; (b) 12 stations along a recreational beach over an 18-month period; and (c) at an underground freshwater seepage point over 1 day. Total coliform (TC), faecal coliform (FC), and faecal streptococci (FS) contamination reported during all surveys varied randomly (e.g., with maximum densities in the ranges of 346-2020 TC, 130-2000 FC, and 180-1040 FS at one site) and at times exceeded the established EEC and Environment Protection Agency (EPA) standards for bathing water (e.g., in >90% of samples) to qualify for beach closure. Computed FC:FS ratios were used to pinpoint human faecal matter as the main source of contamination. Nitrate, phosphate, and silicate concentrations in seepage water were high (3600-9485, 38-105, and 9950-24,775 microg l(-1), respectively) and a cause for concern when compared with levels (5-845, 5-72, and 35-6570 microg l(-1), respectively) in cleaner lagoon water samples. Statistical analysis showed significant correlations (for TC and NO3: r=.75, P<.02; for TC and PO4: r=.779, P<.02; for TC and SiO4: r=.731, P<.05; for FC and NO3: r=.773, P<.02; for FC and SiO4: r=.727, P<.05; for FS and SiO4: r=.801 P<.01) between microbial densities and nutrients recorded, confirming the pathogen-contaminated water to be highly eutrophic. There is an urgency for Mauritius to properly address the issue of sewage treatment and wastewater discharge to safeguard its coastal environment, public health, and tourism expansion.

Spotlight on depression: a Pharma Matters report.

Depression represents a huge pharmaceutical market opportunity. There are approximately 350 million people worldwide with depression, and it is the leading cause of disability in the world. In the U.S., 9.1% of the population suffers from depression. Globally, fewer than half of depression sufferers receive treatment for their illness, and in some countries this figure falls to fewer than 1 in 10. The high incidence rate, combined with limited market penetration, makes depression a high potential market for pharmaceuticals. However, companies developing drugs for depression also face a number of serious challenges. Psychosocial treatment options remain the preferred first-line therapy ahead of medication-and when it comes to drug treatment, the abundance of generic options available has significantly contributed to halving the value of the branded antidepressant market over recent years. Another hurdle faced by new drugs is the requirement that all antidepressants carry a black-box warning regarding the increased risk of suicide in children, adolescents and young adults, which limits their use in this population. Switching between medications presents both an opportunity and a challenge, as a significant number of patients will switch away from their first medication within the first year of treatment. The lack of complete understanding of why depression occurs also makes this area a difficult one, although it opens the door for the development of drugs with novel mechanisms of action.

2012 in review - part II: overcoming the obstacles in the pharma/biotech industry.

As highlighted in the first part of this review published last month, the year 2012 saw the approval of a remarkable number of new drugs, and among the new drugs reaching the market, a significant proportion were orphan drugs developed for treating less prevalent diseases. These drugs are certainly not expected to become blockbusters, but are of high interest because of their efficacy in a narrow spectrum of patients. This trend aligns with the general tendency of staying away from fit-for-all blockbusters into personalized medicine as one of the strategies for overcoming the patent cliff that resulted in a long list of drugs going off patent and being approved as generics also during last year. The emerging scenario resulting from new developments in the form of new drugs and biosimilars and newly available generic medications paralleled by strategic movements within the pharmaceutical industry to reinforce their position in the market, as reflected by merger and acquisition deals accompanied by significant efforts into prioritization resulting in spin-off and split transactions, is reviewed in this second part. This paper includes a significant amount of data in tables for quick review and to profile the new strategic movements in drug pipelines. Further information, including details on mechanisms of action, current status, itemized pharmacology, pharmacokinetic and clinical trial research findings and updated information can be found in the proprietary databases Thomson Reuters Integrity(SM) and Thomson Reuters Cortellis™.

Fostering new investigators in Reproductive Immunology.

During the 8th European Congress of Reproductive Immunology, November 2010 in Munich, Germany, the European Society of Reproductive Immunology provided the opportunity for young investigators to present their work. Short talks from students and post-doctoral trainees were scheduled immediately after the keynote speakers in each session. The Society presented two "Young Investigator Awards" in basic science as well as in clinical application, sponsored by Elsevier. Here we present a summary of the nominees in a single article. The nominees were asked to give a guided interview to provide an insight into their motivation and career aspirations for the future. We hope that the Young Investigator Award might be an ongoing tool to motivate and encourage young investigators to stay in the field of reproductive immunology and to continue their research on the feto-maternal interface.

Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells.

Mature dendritic cells (mDCs) are potent antigen presenting cells, but immature DCs (iDCs) have been shown to have reduced antigen stimulatory capacity. Different strategies have been investigated to augment the tolerogenic capacity of dendritic cells (DCs). We demonstrate that in aspirin-treated human DCs, there is reduced expression of CD1a, HLA-DR and CD86, up-regulation of ILT-3 expression and marginal increases in PDL-1. Aspirin-treated DCs are partially resistant to phenotypic changes following maturational stimuli, such as lipopolysaccharide (LPS) or TNFalpha, IL-1alpha and PGE2. Aspirin-treated DCs demonstrate normal endocytic function, but have a reduced ability to stimulate allogeneic T cells, which is comparable to iDCs. Furthermore, they induce hyporesponsiveness and regulatory activity in responder naïve and memory T cells; for naïve T cells this is achieved more quickly and efficiently than with iDCs. We investigated the mechanism of this regulatory activity and found that both cell-cell contact and inhibitory cytokine activity are involved, although no one cytokine predominates in importance. Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells. Results demonstrate that aspirin-treated DCs display tolerogenic potential, which is of interest in their therapeutic potential in reducing chronic allograft rejection.

Differential expression of CTLA-4 among T cell subsets.

CTLA-4 (CD152), the CD28 homologue, is a costimulatory molecule with negative effects on T cell activation. In addition to its role in the termination of activation, CTLA-4 has been implicated in anergy induction and the function of regulatory cells. As an intracellular molecule, it must first relocate to the cell surface and be ligated, in order to inhibit activation. Although some studies have investigated CTLA-4 expression on CD4(+) T cells, evidence is lacking regarding the kinetics of expression, and expression on T cell subpopulations. We have investigated CTLA-4 kinetics on human purified peripheral CD4(+), naïve, memory, CD4(+)CD25(-), CD4(+)CD25(+) regulatory T cells, and T cell clones. Intracellular stores of CTLA-4 were shown to be very low in naïve T cells, whilst significant amounts were present in memory T cells and T cell clones. Cell surface CTLA-4 expression was then investigated on CD4(+)CD45RA(+) (naïve), CD4(+)CD45RO(+) (memory), CD4(+)CD25(-), and CD4(+)CD25(+) T cells. CD25 and CD45RO are both expressed by regulatory T cells. On naïve and CD4(+)CD25(-) T cells, CTLA-4 expression declined after four hours. In contrast, on memory and CD4(+)CD25(+) T cells, high levels of expression were maintained until at least 48 hours. In addition, significant CTLA-4 expression was observed on T cell clones following anergy induction, indicating the potential involvement of CTLA-4 also in this form of tolerance.