Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS ...Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.
Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.
Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).
Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.
Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival ...in cancer patients.
The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans.
Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013).
Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.
Lean body mass (LBM) is an important prognostic factor in patients with cancer. Although the L3–computed tomography (CT) scan is considered a reference method for assessment, a convenient and easily ...available method for longitudinal follow-up is required. Although bioelectrical impedance analysis (BIA) is widely used, its accuracy is questioned; plasma creatinine-to-cystatin C (CC) ratio could be an attractive alternative. The aim of this study was to evaluate the ability of the CC ratio and BIA to detect myopenia in patients with cancer compared with the use of the CT scan as a standard.
Patients with any kind of cancer had body composition evaluation by CT scan, BIA, and CC. Statistical analysis included correlation test, Bland–Altman, and receiver operating characteristic curve analysis.
Forty-four patients (14 women) were included. Of the participants, 59% had myopenia on CT scan. Both BIA LBM and CC ratio were well correlated with CT scan LBM (r = 0.763 and 0.648, respectively) but concordance analysis revealed a 3-kg constant bias toward BIA compared with CT scan. In terms of ability to detect myopenia, areas under the curve (AUC) for BIA were 0.675 and 0.388 for men and women, respectively. For CC ratio, AUCs were 0.813 and 0.673.
This study demonstrated that LBM assessed by the CC ratio or BIA is well correlated with that determined by L3-CT scan. The ability of the CC ratio to detect myopenia was better than that of BIA. Findings from the present study demonstrated that CC ratio can be conveniently used in patients with cancer as a reliable biomarker of muscularity.
•L3–computed tomography scan is most widely used for body composition evaluation in oncology.•L3–computed tomography scan for body composition in oncology has some shortcomings.•Bioimpedance analysis has a good correlation but poor agreement with L3–computed tomography scan.•The ratio of creatinine to cystatin C can be an alternative for the diagnosis of myopenia.
We studied the microstructure of physical chitosan hydrogels formed by the neutralization of chitosan aqueous solutions highlighting the structural gradients within thick gels (up to a thickness of ...16 mm). We explored a high polymer concentrations range (C p ≥ 1.0% w/w) with different molar masses of chitosan and different concentrations of the coagulation agent. The effect of these processing parameters on the morphology was evaluated mainly through small-angle light scattering (SALS) measurements and confocal laser scanning microscopy (CLSM) observations. As a result, we reported that the microstructure is continuously evolving from the surface to the bulk, with mainly two structural transitions zones separating three types of hydrogels. The first zone (zone I) is located close to the surface of the hydrogel and constitutes a hard (entangled) layer formed under fast neutralization conditions. It is followed by a second zone (zone II) with a larger thickness (∼3–4 mm), where in some cases large pores or capillaries (diameter ∼10 μm) oriented parallel to the direction of the gel front are present. Deeper in the hydrogel (zone III), a finer oriented microstructure, with characteristic sizes lower than 2–3 μm, gradually replace the capillary morphology. However, this last bulk morphology cannot be regarded as structurally uniform because the size of small micrometer-range-oriented pores continuously increases as the distance to the surface of the hydrogel increases. These results could be rationalized through the effect of coagulation kinetics impacting the morphology obtained during neutralization.
Malnutrition is a critical predictor of toxicity and outcome in patients with cancer and may be perceived differently by patients, relatives, and physicians.
To assess the prevalence of malnutrition ...in oncology departments and to compare it with the perceptions of nutrition status by patients themselves, their closest relatives, and attending physicians.
A 1-day multicentric cross-sectional survey on the prevalence of malnutrition was conducted in different oncology departments using patient-, relative-, and physician-specific questionnaires. Malnutrition was defined by a weight loss ≥5% within 1 month or ≥10% within 6 months, a body mass index ≤18.5 kg/m
in patients aged <70 years or ≤21 kg/m
in patients aged ≥70 years, and/or albuminemia <35 g/L. Questionnaires for assessing medical condition, knowledge of nutrition status, and perceptions of the impact of malnutrition on daily life were distributed to consenting patients, attending physicians, and closest relatives.
A total of 2197 patients were included, and 2071 and 976 questionnaires were collected from patients and relatives, respectively. Prevalence of malnutrition was 39%. Physicians overestimated malnutrition (44%), whereas patients and relatives underestimated it (22% and 23%, respectively, P < .001). Conversely, malnutrition-associated symptoms were underestimated by physicians compared with patients and relatives.
We found a prevalence of malnutrition of 39%: it was underestimated by patients and relatives and overestimated by physicians.
Glyphosate is the most used herbicide in the world. Controversial studies exist on its effect on the male reproductive system. We used the validated BioAlter® model to test the effects of low ...concentrations of Glyphosate. Pubertal rat seminiferous tubules were treated with Glyphosate 50 nM, 500 nM, 5 μM or 50 μM over a 3-week culture period. The Trans-Epithelial Electrical Resistance was not modified by any of the concentrations. The decrease of Clusterin mRNAs suggested that glyphosate would target the integrity of Sertoli cells. The decrease of the numbers of germ cells from day 14 onward highlighted the chronic effect of glyphosate at 50 nM, 500 nM or 5 μM. No consistent effect of glyphosate was observed on the numbers of spermatogonia or on their specific mRNA levels. However, those low concentrations of glyphosate targeted young spermatocytes and middle to late pachytene spermatocytes resulting in a decrease of the numbers of round spermatids, the direct precursors of spermatozoa. This study underlines that the effect of a toxicant should be also studied at low doses and during the establishment of the blood-testis barrier.
•Low concentrations of glyphosate: effects on spermatogenesis in vitro•Glyphosate targeted the integrity of Sertoli cells and the meiotic step•Glyphosate induced a decrease of round spermatids
The main objective of this study was to monitor wet snow conditions from Sentinel-1 over a season, to examine its variation over time by cross-checking wet snow with independent snow and weather ...estimates, and to study its distribution taking into account terrain characteristics such as elevation, orientation, and slope. One of our motivations was to derive useful representations of daily or seasonal snow changes that would help to easily identify wet snow elevations and determine melt-out days in an area of interest. In this work, a well-known approach in the literature is used to estimate the extent of wet snow cover continuously over a season and an analysis of the influence of complex mountain topography on snow distribution is proposed taking into account altitude, slope, and aspect of the terrain. The Sentinel-1 wet snow extent product was compared with Sentinel-2 snow products for cloud free scenes. We show that while there are good agreements between the two satellite products, differences exist, especially in areas of forests and glaciers where snow is underestimated. This underestimation must be considered alongside the areas of geometric distortion that were excluded from our study. We analysed retrievals at the scale of our study area by examining wet snow Altitude–Orientation diagrams for different classes of slopes and also wet snow Altitude–Time diagrams for different classes of orientations. We have shown that this type of representation is very useful to get an overview of the snow distribution as it allows to identify very easily wet snow lines for different orientations. For an orientation of interest, the Altitude–Time diagrams can be used to track the evolution of snow to locate altitudes and dates of snow loss. We also show that ascending/descending Sentinel-1 image time series are complementary to monitor wet snow over the French alpine areas to highlight wet snow altitude ranges and identify melt-out days. Links have also been made between Sentinel-1 responses (wet snow) and snow/meteorological events carefully listed over the entire 2017–2018 season.
Background.
Hypertension is a common toxicity of bevacizumab, but the frequency of assessment of blood pressure and standardized grading remain to be defined. This study aimed to describe the ...incidence of bevacizumab‐induced hypertension and factors associated with its development, then to retrospectively assess its relation with activity.
Patients and methods.
One hundred nineteen patients with advanced or metastatic non‐small cell lung cancer, colorectal cancer, or ovarian cancer receiving bevacizumab (2.5 mg/kg per week) and chemotherapy were eligible for this analysis. Blood pressure was measured at home twice daily according to international guidelines, and graded according to the National Cancer Institute Common Toxicity Criteria (NCI‐CTC), version 3.0, and the European Society of Hypertension (ESH) criteria.
Results.
Home‐based measurements detected significantly more cases of hypertension than in‐clinic measurements did, according to the ESH criteria (54.6% versus 24.4%; p < .001) or the NCI‐CTC (42.9% versus 22.7%; p = .0015). Very early hypertension (within 42 days, according to the ESH criteria) but not hypertension (occurring at any time during treatment period) was predictive of response (p = .0011 and p = .26, respectively).
Conclusions.
Our preliminary results indicate that home‐based measurement and grading according to the ESH criteria represents a reliable method to detect bevacizumab‐induced hypertension. Whether hypertension is a biomarker of bevacizumab activity remains to be determined in a prospective study.
摘要
背景. 高血压是贝伐珠单抗导致的常见毒性反应，血压监测频率及标准化分级还有待明确。本研究旨在描述贝伐珠单抗所致高血压的发生率及其发展相关因素，并回顾性评估高血压与贝伐珠单抗活性的关系。
患者与方法.119例接受贝伐珠单抗（每周2.5 mg/kg）和化疗的晚期或转移性非小细胞肺癌、结直肠癌及卵巢癌患者纳入本研究。按国际指南及国立癌症研究院常见毒性标准（NCI‐CTC）3.0版与欧洲高血压学会（ESH）标准，每天在家测两次血压。
结果.按ESH或NCI‐CTC标准，居家测量检出的高血压病例显著多于门诊测量（分别为54.6%#x0025;vs 24.4%#x0025;；p<0.001；42.9%#x0025;vs 22.7%#x0025;；p=0.0015）。极早期出现的高血压（42天内，按ESH标准）可预测疗效，而（治疗期间任何时间出现的）高血压无法预测（分别为p=0.0011和p=0.26）。
结论.本研究初步结果表明，居家测量及按ESH标准分级可有效检出贝伐珠单抗所致高血压。高血压能否作为贝伐珠单抗活性的生物标志物有待前瞻性研究的证实。
The incidence of bevacizumab‐induced hypertension and factors associated with its development are described, and its relation with activity is retrospectively assessed. A reliable method for the detection and grading of hypertension is determined and recommendations for further studies aiming to study hypertension as a biomarker for bevacizumab efficacy are established.
The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined.
To establish and compare the fatty acid, ...tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO).
The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC).
The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels.
Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.
In response to the EU cosmetics directive regulation and REACH legislation which encourage cell culture methods in order to reduce or replace the use of animals in toxicology studies, we settled the ...culture of prepubertal domestic cat seminiferous tubules in our validated BioAlter® model, usually used with prepubertal rat, called here BioAlter®-rat, by opposition to BioAlter®-cat settled here. We carried out a comparative study on the effects of 3 testicular toxicants, 1,3-dinitrobenzene at 60 μM, 2-methoxyacetic acid at 2.5 mM and carbendazim at 50 nM or 500 nM in both BioAlter®-cat and BioAlter®-rat over a 3-week culture period. Sertoli cell or each germ cell populations as well as the levels of Sertoli cell or germ cell specific mRNAs were studied. The harmful effects of the 3 toxicants on pre-meiotic, meiotic and post-meiotic cell numbers and on Sertoli or germ cell specific mRNAs were clearly observed in the two species, even if there might be some small differences in the intensity of the effects on some of the studied parameters. Hence, BioAlter®-cat might be a solution to the requirements of the EU cosmetics directive and REACH legislation for male reproductive toxicology studies.
•Settlement of the culture of prepubertal domestic cat seminiferous tubules.•A comparative study of rat or cat seminiferous tubule cultures in BioAlter®.•BioAlter®-cat successfully detects the testicular toxicity of DNB, MAA and CBZ.•BioAlter®-cat: an alternative method for male in vitro reproductive toxicology.
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