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Chemosphere Apr 2017Phthalic acid esters have been widely used to improve the plasticity of PVC medical devices. They carry a high exposure risk for both humans and the environment in...
Phthalic acid esters have been widely used to improve the plasticity of PVC medical devices. They carry a high exposure risk for both humans and the environment in clinical situations. Our study focuses on the cytotoxicity of alternative plasticizers. Postulated primary metabolites were synthesized, not being commercially available. Cytotoxicity assays were performed on L929 murine cells according to the ISO-EN 10993-5 standard design for the biocompatibility of medical devices. The tested concentrations of plasticizers (0.01, 0.05 and 0.1 mg/ml) covered the range likely to be found in biological fluids coming into direct contact with the medical devices. DEHP, DINP and DINCH were cytotoxic at the highest concentration (0.1 mg/ml) for 7 days of exposure. Their corresponding metabolites were found to be more cytotoxic, for the same concentration. By contrast, TOTM and its corresponding metabolite MOTM were not found to be cytotoxic. DEHA showed no cytotoxicity, but its corresponding monoester (MEHA) produced a cytotoxic effect at 0.05 mg/ml. In clinical situations, medical devices can release plasticizers, which can come into contact with patients. In vivo, the plasticizers are quickly transformed into primary metabolites. It is therefore important to measure the effects of both the plasticizers and their corresponding metabolites. Standard first-line cytotoxicity assays should be performed to ensure biocompatibility.
Topics: Animals; Cell Survival; Cells, Cultured; Diethylhexyl Phthalate; Esters; Fibroblasts; In Vitro Techniques; Mice; Phthalic Acids; Plasticizers; Polyvinyl Chloride
PubMed: 28129623
DOI: 10.1016/j.chemosphere.2017.01.026 -
International Journal of Surgical... Dec 2023
Topics: Humans; Dendritic Cell Sarcoma, Follicular; Dendritic Cells, Follicular; Proto-Oncogene Proteins c-mdm2
PubMed: 37016745
DOI: 10.1177/10668969231160260 -
Journal of Market Access & Health Policy 2019: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best...
: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. : A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. : Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. : Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.
PubMed: 31275535
DOI: 10.1080/20016689.2019.1626171 -
Colorectal Disease : the Official... Jul 2021Identification of the risks of postoperative complications may be challenging in older patients with heterogeneous physical and cognitive status. The aim of this... (Observational Study)
Observational Study
The Clinical Frailty Scale is a useful tool for predicting postoperative complications following elective colon cancer surgery at the age of 80 years and above: A prospective, multicentre observational study.
AIM
Identification of the risks of postoperative complications may be challenging in older patients with heterogeneous physical and cognitive status. The aim of this multicentre, observational study was to identify variables that affect the outcomes of colon cancer surgery and, especially, to find tools to quantify the risks related to surgery.
METHOD
Patients aged ≥80 years with electively operated Stage I-III colon cancer were recruited. The prospectively collected data included comorbidities, results of the onco-geriatric screening tool (G8), Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI) and Mini Nutritional Assessment-Short Form (MNA-SF), and operative and postoperative outcomes.
RESULTS
A total of 161 patients (mean 84.5 years, range 80-97, 60% female) were included. History of cerebral stroke (64% vs. 37%, p = 0.02), albumin level 31-34 g/l compared with ≥35 g/l (57% vs. 32%, p = 0.007), CFS 3-4 and 5-9 compared with CFS 1-2 (49% and 47% vs. 16%, respectively) and American Society of Anesthesiologists score >3 (77% vs. 28%, P = 0.006) were related to a higher risk of complications. In multivariate logistic regression analysis CFS ≥3 (OR 6.06, 95% CI 1.88-19.5, p = 0.003) and albumin level 31-34 g/l (OR 3.88, 1.61-9.38, p = 0.003) were significantly associated with postoperative complications. Severe complications were more common in patients with chronic obstructive pulmonary disease (43% vs. 13%, p = 0.047), renal failure (25% vs. 12%, p = 0.021), albumin level 31-34 g/l (26% vs. 8%, p = 0.014) and CCI >6 (23% vs. 10%, p = 0.034).
CONCLUSION
Surgery on physically and cognitively fit aged colon cancer patients with CFS 1-2 can lead to excellent operative outcomes similar to those of younger patients. The CFS could be a useful screening tool for predicting postoperative complications.
Topics: Aged; Aged, 80 and over; Colonic Neoplasms; Female; Frailty; Geriatric Assessment; Humans; Male; Postoperative Complications; Prospective Studies; Risk Factors
PubMed: 33915013
DOI: 10.1111/codi.15689 -
International Journal of Molecular... Jul 2018Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells...
Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells during and after their injection by encapsulation in a hydrogel using a droplet millifluidics technique. A biocompatible, self-hardening biomaterial composed of silanized-hydroxypropylmethylcellulose (Si-HPMC) hydrogel was used and dispersed in an oil continuous phase. Spherical particles with a mean diameter of 200 μm could be obtained in a reproducible manner. The viability of the encapsulated hASCs in the Si-HPMC particles was 70% after 14 days in vitro, confirming that the Si-HPMC particles supported the diffusion of nutrients, vitamins, and glucose essential for survival of the encapsulated hASCs. The combination of droplet millifluidics and biomaterials is therefore a very promising method for the development of new cellular microenvironments, with the potential for applications in biomedical engineering.
Topics: Biocompatible Materials; Cell Differentiation; Cells, Cultured; Humans; Hydrogels; Hypromellose Derivatives; Mesenchymal Stem Cells
PubMed: 29970871
DOI: 10.3390/ijms19071952 -
Nature Communications Jan 2018The originally published version of this Article contained an error in Equation 30, which was inadvertently introduced during the production process. This has now been...
The originally published version of this Article contained an error in Equation 30, which was inadvertently introduced during the production process. This has now been corrected in the PDF and HTML versions of the Article.
PubMed: 29386503
DOI: 10.1038/s41467-018-03023-3 -
International Journal of Hygiene and... Apr 2019Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been...
BACKGROUND
Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been contested by the European authorities since 2008. Several alternative plasticizers are being considered to replace DEHP, such as DEHT, TOTM, DINP or DINCH, but they are also released from the PVC throughout their life cycle and are metabolized in the same way as DEHP.
OBJECTIVES
Our study focuses on the in vitro cytotoxicity of two alternative plasticizers (DINCH and DINP) contained in certain medical devices. They are likely to migrate and be transformed in vivo into the primary and secondary metabolites by a metabolism similar to that of DEHP. This preliminary study is the first to assess the in vitro cytotoxicity of oxidized metabolites of DINCH and DINP based on the EN ISO 10-993-5 standards documents.
METHODS
We have studied the complete multi-step organic synthesis of secondary metabolites of DINP and DINCH and have performed cytotoxicity tests on L929 murine cells according to the EN ISO 10993-5 standard design for the biocompatibility of a MD. The tested concentrations of obtained metabolites (0.01, 0.05 and 0.1 mg/mL) covered the range likely to be found for DEHP (total metabolism) in biological fluids coming into direct contact with the MD. The concentrations tested in our study were chosen based on a complete transformation of the plasticizers released after direct contact between a MD and the patient's blood.
RESULTS
Only 7-oxo-MMeOCH is cytotoxic at the highest concentration (0.1 mg/mL) after 7 days of exposure, just like 5-oxo-MEHP for the same concentration. By contrast, 7-OH-MMeOP, 7-cx-MMeOP, 7-oxo-MMeOP, 7-OH-MMeOCH and 7-cx-MMeOCH were not found to be cytotoxic.
CONCLUSION
The known concentrations of these secondary metabolites in urinary samples are in the μg/L range, i.e. about 100-1000 times lower than the concentrations tested in this study. Cytotoxicity is known to be dose-dependent but it is not always the case for endocrine perturbations and the secondary metabolites could induce endocrine perturbations at very low doses.
Topics: Animals; Cell Line; Cell Survival; Cyclohexanecarboxylic Acids; Dicarboxylic Acids; Diethylhexyl Phthalate; Equipment and Supplies; Mice; Phthalic Acids; Plasticizers
PubMed: 30898526
DOI: 10.1016/j.ijheh.2019.03.005 -
Antimicrobial Agents and Chemotherapy Sep 2020Although remains the major etiological agent of invasive candidiasis, and other emerging species of are increasingly isolated. This species is the second most...
Although remains the major etiological agent of invasive candidiasis, and other emerging species of are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of and can be misidentified and are underdiagnosed due to phenotypic traits shared with Little is known about the two cryptic species. Therefore, pathogenesis studies are needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of to different species makes this nematode an excellent model for assessing host-fungus interactions. We evaluated the usefulness of as a nonconventional host model to analyze the virulence of , , and The three species caused candidiasis, and the highest virulence of was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the model. Amphotericin B and azoles showed the highest activity against and infections, while echinocandins were more active for treating those caused by proved to be a useful model system for assessing the pathogenicity of these closely related species.
Topics: Animals; Antifungal Agents; Caenorhabditis elegans; Candida; Candida glabrata; Microbial Sensitivity Tests; Saccharomycetales; Virulence
PubMed: 32718968
DOI: 10.1128/AAC.00824-20 -
Acta Obstetricia Et Gynecologica... Sep 2016The success of the primary repair of obstetric anal sphincter injury (OASI) is paramount in maintaining adequate fecal continence after childbirth. The factors...
INTRODUCTION
The success of the primary repair of obstetric anal sphincter injury (OASI) is paramount in maintaining adequate fecal continence after childbirth. The factors determining the success or failure of primary repair are unclear. The aim of this study is to investigate modifiable factors determining the success or failure of the primary sphincter repair after OASI.
MATERIAL AND METHODS
Sixty women with OASI were investigated by endoanal ultrasound or magnetic resonance imaging, and with the Wexner incontinence questionnaire. Based on the findings, the women were divided in two groups; successful primary repair group (n = 41) and failed primary repair group (n = 19).
RESULTS
The primary repair failed in 31.7% of the tears. These included more tears repaired by less experienced personnel (p < 0.001) and more repairs performed during on-call hours (p = 0.039) than in the successful primary repair group. Significantly more pain medication was used in the failed group (p = 0.003), and the use of antibiotics and laxatives after the repair was more common in the successful group (p < 0.001). Sphincter injuries were repaired using the overlapping suture technique in 95.1% of the repairs in the successful group compared with 47.4% in the failed group (p = 0.03). The mean (SD) Wexner score was significantly higher in the failed group [5.92 (4.1) vs. 1.88 (4.2), p < 0.001], in agreement with the findings on endoanal ultrasound.
CONCLUSIONS
Postpartum perineal tears should be evaluated by personnel familiar with the diagnosis and repair of OASI. Delaying the primary repair until next morning is recommended if experienced personnel are unavailable during on-call hours.
Topics: Adult; Anal Canal; Analgesics; Anti-Bacterial Agents; Clinical Competence; Delivery, Obstetric; Drug Utilization; Endosonography; Fecal Incontinence; Female; Humans; Laxatives; Magnetic Resonance Imaging; Perineum; Pregnancy; Suture Techniques; Time-to-Treatment; Treatment Failure; Young Adult
PubMed: 27100274
DOI: 10.1111/aogs.12909 -
Annals of Surgical Oncology Oct 2023Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real...
BACKGROUND
Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real advantage.
METHODS
Consecutive patients undergoing NSM for cancer with omission of IERM according to institutional protocols from 2016 to 2021 were retrospectively analyzed. The decision to maintain or remove the Nipple-Areola Complex (NAC) after definitive pathology was taken at the multidisciplinary meeting.
RESULTS
Among 162 women operated in the study period, the presence of neoplastic cells within 2 mm from the inked retroareolar margin (RAM) was detected at permanent pathology in 17 cases (10.5%). Nipple-Areola-Complex (NAC) was removed postoperatively in five patients (3%) for margins <1 mm, the other 12 were observed, whereas postoperative NAC necrosis required surgical removal in additional five cases (3%). The NAC was thus preserved in 152 of 162 patients (94%). At multivariate analysis, RAM ≤2 mm was associated with radiological tumor-to-nipple distance less than or equal to 1 cm (p = 0.04) and Ki67 label index ≥ 20 (p = 0.04), whereas multifocality/multicentricity showed a trend towards significance (p = 0.07). At a median follow-up of 46 months, five locoregional relapses occurred (3%), only one of them involving the NAC (0, 6%). Locoregional relapse and overall survival for patients with RAM > or < 2 mm were not different.
CONCLUSIONS
IERM is not routinely necessary during NSM for cancer, because its omission is associated with a very low return to the operating room, it is oncologically safe, and associated pitfalls are avoided. Further studies are necessary to confirm these findings.
Topics: Humans; Female; Mastectomy; Nipples; Retrospective Studies; Breast Neoplasms; Mastectomy, Subcutaneous; Mammaplasty
PubMed: 37391672
DOI: 10.1245/s10434-023-13726-7