Contribution of blood detection of insulin-like growth factor binding protein-1 for the diagnosis of amniotic-fluid embolism: a retrospective multicentre cohort study.

OBJECTIVE: To assess the contribution of maternal blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism in clinical daily practice. DESIGN: A retrospective multicentre cohort study. SETTING: Three tertiary care obstetric units in France. SAMPLE: Data of 86 women for whom amniotic-fluid embolism had been suspected and maternal serum detection of IGFBP-1 had been performed between 2011 and 2019 were analysed. METHODS: The criteria defined by the United Kingdom Obstetric Surveillance System (UKOSS) were used for the retrospective diagnosis of amniotic-fluid embolism. The more structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation (SMFM) was also used as secondary endpoint. MAIN OUTCOME MEASURES: Agreements between biological and clinical assessments were tested. The performance of blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism according to the UKOSS criteria, and to the SMFM definition, was also assessed. RESULTS: There was only slight agreement between clinical and laboratory diagnosis of amniotic-fluid embolism (Cohen's Kappa coefficient: 0.04). Blood detection of IGFBP-1 had a sensitivity of 16%, a specificity of 88%, a positive and a negative likelihood ratio of 1.3 and 0.95, respectively, and a positive and a negative predictive value of 58 and 50%, respectively, for the diagnosis of amniotic-fluid embolism based on the UKOSS criteria. The use of the more structured SMFM definition of amniotic-fluid embolism did not substantially change the results. CONCLUSION: These results question the usefulness of blood detection of IGFBP-1 for the early diagnosis of amniotic-fluid embolism in daily clinical practice. TWEETABLE ABSTRACT: This retrospective multicentre study questions the contribution of IGFBP-1 detection for the diagnosis of AFE.

Stability of the Zhang-Rice Singlet with Doping in Lanthanum Strontium Copper Oxide Across the Superconducting Dome and Above.

The spin character of the states at the top of the valence band in doped La(2-x)Sr(x)CuO(4) (x=0.03, 0.07, 0.15, 0.22, and 0.30) has been investigated using spin-polarized resonant photoemission. A clear Zhang-Rice singlet (ZRS) is observed at all doping levels. Its stability and polarization are preserved as a function of doping, suggesting that the concept of the ZRS can be used across a wide doping range and up to the metallic nonsuperconducting overdoped regime. The results are significant for theoretical models that use the ZRS approximation and for the understanding of the peculiar interplay between the ZRS and the remaining localized spins.

Active surveillance in favorable intermediate-risk prostate cancer: A single-center experience.

PURPOSE: To report the long-term oncological outcomes of active surveillance (AS) in selected patients with favorable intermediate-risk (IR) prostate cancer (PCa). METHODS: A retrospective database review of two academic centers was conducted to identify favorable IR PCa patients initially managed by AS between 2014 and 2022. Favorable IR PCa was defined by the presence of one single element of IR disease (i.e., PSA 10-20ng/mL, Gleason Grade Group [GG] 2, or cT2b). All patients were diagnosed and followed up according to a contemporary scheme, including MRI and image-guided biopsies. The primary endpoint was metastasis-free survival. RESULTS: A total of 57 patients met our inclusion criteria and the median follow-up was 56months. During follow-up, there were no cases of metastasis or death due to PCa, but 6 deaths due to competing causes. A total of 25 (44%) and 6 patients (11%) had definitive treatment and GG 3 reclassification during follow-up, respectively. In multivariable Cox hazard regression analysis, the risk of undergoing definitive treatment was significantly associated with PSA density>0.15 (HR: 4.82, 95% CI: 1.47 to 15; P=0.01) and PI-RADS 4-5 lesions on mpMRI (HR: 2.48, 95% CI: 1.06 to 5.19; P=0.006). Interestingly, tumor burden (P=0.3) and GG (P=0.7) on biopsy were not associated with definitive treatment. CONCLUSIONS: AS is a safe and valuable strategy for well-selected patients with favorable IR prostate cancer, with excellent oncological outcomes after five years' follow-up.

Active surveillance of low-grade prostate cancer using the SurACaP Criteria: A multi-institutional series with a median follow-up of 10years.

PURPOSE: To report on the oncological outcomes of active surveillance (AS) in low-grade prostate cancer (PCa) patients using the French SurACaP protocol, with a focus on long-term outcomes. METHODS: This multicenter study recruited patients with low-grade PCa between 2007 and 2013 in four referral centers in France. The cohort included patients meeting the SurACaP inclusion criteria, i.e., aged ≤75years, with low-grade PCa (i.e., ISUP 1), clinical stage T1c/T2a, PSA ≤10ng/mL and ≤3 positive cores and tumor length ≤3mm per core. The SurACaP protocol included a digital rectal examination every six months, PSA level measurement every three months for the first two years after inclusion and twice a year thereafter, a confirmatory biopsy in the first year after inclusion, and then follow-up biopsy every two years or if disease progression was suspected. Multiparametric magnetic resonance imaging (mpMRI) was progressively included over the study period. RESULTS: A total of 86 consecutive patients were included, with a median follow-up of 10.6 years. Only one patient developed metastases and died of PCa. The estimated rates of grade reclassification and treatment-free survival at 15 years were 53.4% and 21.2%, respectively. A negative mpMRI at baseline and a negative confirmatory biopsy were significantly associated with a lower risk of disease progression (P<0.05). CONCLUSIONS: AS using the French SurACaP protocol is a safe and valuable strategy for patients with low-risk PCa, with excellent oncological outcomes after more than 10 years' follow-up. Future studies are crucial to broaden the inclusion criteria and develop a personalized, risk based AS protocol with the aim of de-escalating follow-up examinations. LEVEL OF EVIDENCE: Grade 4.

Heavy element enhanced synchrotron stereotactic radiotherapy as a promising brain tumour treatment.

Synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumours followed by stereotactic irradiation, in CT mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, characteristic X-rays, photoelectrons, and Auger electrons generated on high-Z atoms by kilovoltage X-rays produce a localized dose enhancement. Two complimentary SSR approaches have been successfully developed in the past 5 years in our team, and may be promising in high-grade glioma management: iodine-enhanced SSR, with an iodinated contrast agent; and Pt-enhanced SSR; a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. The results for iodine-enhanced SSR using contrast agents are presented in this paper. IUdR-enhanced SSR was also tested in this study. Up to 15 Gy, intracarotid infusion of iodine significantly improved the rats' survival compared to irradiation alone. SSR provides the most protracted survivals of F98 glioma-bearing rats. The technique is currently transferred to clinical trials. Iodine-enhanced SSR will be implemented first, because of its simplicity; and pave the way for Pt-enhanced SSR, the most efficient technique, but still needing to be improved in terms of intrinsic toxicity.

Variability in women's desire for information about mammography screening: implications for informed consent.

This study aimed to explore women's desire for information about mammography screening in a population where overly optimistic perceptions of mammography screening were common. A self-administered questionnaire was completed by 2305 women aged 50-69 years, residents of Geneva, Switzerland. The questionnaire assessed the respondents' wish to receive information (detailed, general or none) about seven aspects of mammography screening: personal risk of breast cancer, prevention of breast cancer, benefits of mammography screening, limitations, minor inconveniences, more important problems, why some people oppose screening. The seven items formed a unidimensional scale (Cronbach's alpha=0.91). Women differed considerably in their stated desire for detailed or general information. For instance, whereas 14% wanted detailed information on all items and 36% general information on all items, 39% were not interested in detailed information on the limits and adverse consequences of screening. In multivariate analysis, some women's characteristics were associated with higher scores of desire for information, but little variance was explained (adjusted R=0.05). In conclusion, many women currently decline information about mammography screening that is deemed relevant by public health authorities. This may lead to poorly informed choices in an important area of prevention.

Predicting stages of adoption of mammography screening in a general population.

This study assessed predictions of the Transtheoretical Model (TTM) of behaviour change applied to mammography screening in a random sample of 909 Swiss women aged 40-80 years. We examined stages of mammography adoption, positive and negative attitudes toward screening (pros, cons and decisional balance), and additional predisposing, enabling and reinforcing characteristics. The stage of mammography adoption was defined for 827 women, of whom 46.9% reported on-schedule screening (action 10.2%, maintenance 29.7%, relapse risk 7.0%) and 53% did not (precontemplation 23.1%, contemplation 13.5%, relapse 16.4%). Independent factors associated with more advanced stages (from precontemplation to maintenance) were high pros, low cons, belief that mammography screening is recommended every 2 years, high objective risk of breast cancer, being married and higher income. Independent correlates of stage regression (from action/maintenance to relapse) were high cons, belief that mammography screening is recommended every 4 years or not at all and not being married. Perceived utility of an organised screening programme and reluctance to pay for a mammogram were independently associated with only certain transitions between stages of adoption. Our results confirm the applicability of the TTM to mammography screening in a European context. They also suggest that constructs other than pros and cons may be useful in predicting mammography use.

Inhibition of human immunodeficiency virus type 1 replication by phosphonoformate- and phosphonoacetate-2',3'-dideoxy-3'-thiacytidine conjugates.

The synthesis of potential "combined prodrugs" where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 microM, while IC50 for BCH-189 in this system was 0.1 microM. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t1/2 values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti-HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.

Synthesis and antiviral activity of new carbonylphosphonate 2',3'-dideoxy-3'-thiacytidine conjugates.

The synthesis of new potential PFA-BCH-189 conjugate analogues is described and their molecular structure clearly identified through NMR and mass spectra techniques. The anti-HIV-1 activity was determined according to the inhibition of syncytium formation in MT-4 cells, while the anti-HBV activity was determined in infected duck hepatocytes. Both antiviral activities of the PFA-BCH-189 conjugates were much lower than those of the parent BCH-189 (2',3'-dideoxy-3'-thiacytidine) (1). Whereas a prodrug effect, following cleavage and release of the free BCH-189 and PFA, cannot be ruled out, poor cellular permeation of the drug seems to be the most likely reason for the reduced activities against HIV and DHBV. The presence of the PFA moiety appears to be detrimental for both the anti-HIV and anti-DHBV activity of PFA-BCH-189 cases.

Lack of cell death enhancement after irradiation with monochromatic synchrotron X rays at the K-shell edge of platinum incorporated in living SQ20B human cells as cis-diamminedichloroplatinum (II).

In this paper we describe the results of experiments using synchrotron radiation to trigger the Auger effect in living human cancer cells treated with a widely used chemotherapy drug: cis-diamminedichloroplatinum (II) (cisplatin). The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, which produces a high-fluence monochromatic beam that is adjustable from 20 to 80 keV. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. At a low dose of cisplatin (0.1 microM, 48 h), no difference was seen in survival when the cells were irradiated above and below the K-shell edge of platinum. Higher cisplatin concentrations were investigated to enhance the cellular platinum content. The results with 1 microM cisplatin for 12 h showed no difference when the cells were irradiated with beams above or below the platinum K-shell edge with the exception of the higher cell death resulting from drug toxicity. The intracellular content of platinum was significant, as measured macroscopically by inductively coupled plasma mass spectrometry. Its subcellular localization and particularly its presence in the cell nucleus were verified by microscopic synchrotron X-ray fluorescence. This was the first known attempt at K-shell edge photon activation of stable platinum in living cells with a platinum complex used for chemotherapy. Its evident toxicity in these cells leads us to put forth the hypothesis that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. However, K-shell edge photon activation of stable elements provides a powerful technique for the understanding of the biological effects of Auger processes. Further avenues of development are discussed.

Performance of computed tomography for contrast agent concentration measurements with monochromatic x-ray beams: comparison of K-edge versus temporal subtraction.

We investigated the performance of monochromatic computed tomography for the quantification of contrast agent concentrations. Two subtraction methods (K-edge subtraction and temporal subtraction) were evaluated and compared theoretically and experimentally in terms of detection limit, precision and accuracy. Measurements were performed using synchrotron x-rays with Lucite phantoms (10 cm and 17.5 cm in diameter) containing iodine or gadolinium solutions ranging from 50 microg ml(-1) to 5 mg ml(-1). The experiments were carried out using monochromators developed at the European Synchrotron Radiation Facility (ESRF) medical beamline. The phantoms were imaged either above and below the contrast agent K-edge, or before and after the addition of the contrast agent. Both methods gave comparable performance for phantoms less than 10 cm in diameter. For large phantoms, equivalent to a human head, the temporal subtraction is more suitable for detecting elements such as iodine, keeping a reasonable x-ray dose delivered to the phantom. A good agreement was obtained between analytical calculations, simulations and measurements. The beam harmonic content was taken into account in the simulations. It explains the performance degradation with high contrast agent concentrations. The temporal subtraction technique has the advantage of energy tunability and is well suited for imaging elements, such as iodine or gadolinium, in highly absorbing samples. For technical reasons, the K-edge method is preferable when the imaged organ is moving since the two measurements can be performed simultaneously, which is mandatory for obtaining a good subtraction.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility.

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

[A new X-ray source for medical imaging and radiotherapy research: synchrotron radiation]. / Une nouvelle source de rayons X pour la recherche en imagerie médicale et en radiothérapie: le rayonnement synchrotron.

Whether for diagnosis or therapeutic purposes, X-rays have many applications in medicine. Synchrotron Radiation sources open new perspectives. This has already been the case for a number of years in molecular and cellular biology where the scope of absorption and diffraction work has been greatly extended. This could also be the case for medical imaging and radiotherapy where the characteristics of the beam (collimation, stability, flux) allow new approaches in the energy range of radiological X-rays, namely between 30 keV and 100 keV. Such a source exists today in Grenoble, with the European Synchrotron Radiation Facility (ESRF). The opening of a beamline dedicated to medical research for whole European scientific community is planned for the end of 1996. This beamline, coupled with the "microbeam" beamlines, will cover medical imaging (angiography, tomodensitometry, microtomography, X-ray microscopy) as well as radiotherapy.

[Pulmonary embolism of cement during vertebroplasty]. / Embolie pulmonaire au ciment au cours d'une vertébroplastie.

A 62-year-old woman with severe osteoporosis experienced pulmonary embolism by polymethylmethacrylate after percutaneous vertebroplasty. The patient immediately developed respiratory and cardiac distress, and a computed tomographic scan revealed the presence of cement in the pulmonary circulation. Proper techniques can minimize the risk of pulmonary embolism during percutaneous vertebroplasty: adequate preparation of cement and fluoroscopy during the procedure are recommended.

Optimization of bubble column performance for nanoparticle collection.

Fibrous media embody the most effective and widely used method of separating ultrafine particles from a carrier fluid. The main problem associated with them is filter clogging, which induces an increasingly marked pressure drop with time and thus imposes regular media cleaning or replacement. This context has prompted the idea of investigating bubble columns, which operate at constant pressure drop, as alternatives to fibrous filters. This study examines the influence of different operating conditions, such as liquid height, air flow rate, bubble size and presence of granular beds on ultrafine particle collection. Experimental results show that bubble columns are characterised by high collection efficiency, when they feature a large liquid height and small diameter bubbling orifices, while their efficiencies remain lower than those of fibrous filters. Gas velocity does not greatly influence collection efficiency, but the inclusion of a granular bed, composed of beads, increases the bubble residence time in the column, thereby increasing the column collection efficiency.

Can bubble columns be an alternative to fibrous filters for nanoparticles collection?

The most effective and widely used dedusting techniques to separate nanoparticles of a carrier fluid are fibrous media. The main problem is the clogging of the filter that induces a pressure drop increase over time and thus requires a regular cleaning of the media (or its replacement). Following these observations, this study proposes to investigate the potential of bubble columns for nanoparticles collection. Despite collection efficiencies lower than those of fibrous filters, experimental results show that bubble columns present likely performances for the collection of nanoparticles and have collection efficiency even more important when the liquid height is high and bubbling orifices have low diameters. Experiments have also revealed the presence of a most penetrating particle size for a particle diameter range between 10 and 30 nm. The model developed in this article highlights a good agreement between the theoretical collection efficiency by Brownian diffusion and experimental collection efficiencies for particles lower than 20 nm. Nevertheless, the modelling may be extended to other collection mechanisms in order to explain the collection efficiency increase for particles higher than 20 nm and to confirm or infirm that electrostatic effects can be the cause of this efficiency increase.

Patient assessments of a hypothetical medical error: effects of health outcome, disclosure, and staff responsiveness.

OBJECTIVE: To assess whether patients' perceptions of a hypothetical medical error are influenced by staff responsiveness, disclosure of error, and health consequences of the error. DESIGN: Hypothetical scenario describing a medication error submitted by mail. Three factors were manipulated at random: rapid v slow staff responsiveness to error; disclosure v non-disclosure of the error; and occurrence of serious v minor health consequences. PARTICIPANTS: Patients discharged from hospital. MEASURES: Assessment of care described in the scenario as bad or very bad, rating of care as unsafe, and intent to not recommend the hospital. RESULTS: Of 1274 participants who evaluated the scenario, 71.4% rated health care as bad or very bad, 60.2% rated healthcare conditions as unsafe, and 25.5% stated that they would not recommend the hospital. Rating health care as bad or very bad was associated with slow reaction to error (odds ratio (OR) 2.8, 95% CI 2.1 to 3.6), non-disclosure of error (OR 2.0, 95% CI 1.5 to 2.6), and serious health consequences (OR 3.4, 95% CI 2.6 to 4.5). Similar associations were observed for rating healthcare conditions as unsafe and the intent to not recommend the hospital. Younger patients were more sensitive to non-disclosure than older patients. CONCLUSIONS: Former patients view medical errors less favorably when hospital staff react slowly, when the error is not disclosed to the patient, and when the patient suffers serious health consequences.

The synchrotron beam, a new dimension for contrast media research?

Synchrotron sources can provide intense, collimated and tunable X-ray beams suitable for medical imaging and research, allowing the use of monochromatic X-rays for human examinations. At the European Synchrotron Radiation Facility (ESRF), a beam line dedicated to medical research is under commissioning. Two imaging programs are being developed, for coronary angiography and cerebral CT. The new monochromatic imaging systems should improve image contrast and provide better image quantification. The properties of synchrotron radiation are described, as well as the instrumentation of the medical beam line and its 2 imaging programs. The new possibilities offered by synchrotron radiation for contrast media research are discussed, the improvement on concentration measurement precision achievable is underlined.

Tetrazole isosteres of biologically active acids and their effects on enzymes.

A number of tetrazole analogs of carboxylic substrates and inhibitors have been tested. Lactic and pyruvic tetrazoles were found to be competitive inhibitors of rabbit muscle L-lactate dehydrogenase in both the pyruvate reduction and the lactate oxidation reactions (Ki's of 0.04 M and 0.08 M D,L-lactic tetrazole and 0.02 M and 0.035 M pyruvic tetrazole, respectively). Lactic tetrazole is a non-competitive inhibitor of yeast L-lactate dehydrogenase (Ki = 0.10 M D,L-lactic tetrazole) while pyruvic tetrazole is predominantly competitive (Ki = 0.15 M). Alanine tetrazole is a poorer substrate than alanine for D-amino acid oxidase. It also acts as weak inhibitor. Benzoic tetrazole is a substrate-competitive inhibitor of D-amino acid oxidase (Ki = 0.7 mM) and is also a stronger ethanol-competitive inhibitor than benzoic acid (Ki = 0.03 M) of liver alcohol dehydrogenase. In all the substrates and inhibitors tested, substitution of a tetrazole ring for a carboxylic group has resulted in decreased binding, presumably due to a dilution of the negative charge density and the larger size of the tetrazoyl anion.