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In clinical ion beam therapy, protons as well as heavier ions such as carbon are used for treatment. For protons, β+-emitters are only induced by fragmentation reactions in the target (target fragmentation), whereas for heavy ions, they are additionally induced by fragmentations of the projectile (further referred to as autoactivation). An approach utilizing these processes for treatment verfication, by comparing measured Positron Emission Tomography (PET) data to predictions from Monte Carlo simulations, has already been clinically implemented. For an accurate simulation, it is important to consider the biological washout of β+-emitters due to vital functions. To date, mathematical expressions for washout have mainly been determined by using radioactive beams of 10C- and 11C-ions, both β+-emitters, to enhance the counting statistics in the irradiated area. Still, the question of how the choice of projectile (autoactivating or non-autoactivating) influences the washout coefficients, has not been addressed.In this context, an experiment was carried out at the Heidelberg Ion Beam Therapy Center with the purpose of directly comparing irradiation-induced biological washout coefficients in mice for protons and 12C-ions. To this aim, mice were irradiated in the brain region with protons and 12C-ions and measured after irradiation with a PET/CT scanner (Siemens Biograph mCT). After an appropriate waiting time, the mice were sacrificed, then irradiated and measured again under similar conditions. The resulting data were processed and fitted numerically to deduce the main washout parameters.Despite the very low PET counting statistics, a consistent difference could be identified between 12C-ion and proton irradiated mice, with the 12C data being described best by a two component fit with a combined medium and slow washout fraction of 0.50 ± 0.05 and the proton mice data being described best by a one component fit with only one (slow) washout fraction of 0.73 ± 0.06. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenia is a clinical condition defined as low skeletal muscle mass and function. It has been identified and described as a geriatric syndrome, but it may arise in individuals with obesity at any age., Aim: screen for sarcopenia in obese adults and identify the nutritional, clinical and biological risk factors associated with the development of sarcopenic obesity (SO+)., Methods: Descriptive cross-sectional study, including 53 obese patients. Screening for sarcopenia has been established according to pathological thresholds proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO)., Results: Mean age was 44.34±13.51 years. Prevalence of Sarcopenia was 7.5% (SO+). The average intakes of calorie, lipids and saturated fatty acids were higher in SO+. A statistically significant relationship was found between low skeletal muscle mass (SMM/W) and the average intake of vitamin PP (p=0.014) and vitamin B9 (p=0.009). Mean BMI (45.86 kg/m² for SO+ versus 39.29 kg/m² for SO-; p=0.03) and mean visceral fat (16.55 l for SO+, versus 10.93 l for SO-; p=0.043) were significantly higher in SO+. A statistically significant relationship was found between insulin resistance and low (SMM/W), as attested by mean insulinemia (28.81 µIU/mL for low SMM/W, versus 14.48 µIU/mL for normal SMM/W; p=0.004) and HOMA index (7.94 for low SMM/W, versus 3.49 for normal SMM/W; p=0.002), which were higher in cases of low (SMM/W)., Conclusion: We recommend promoting a balanced, low-energy-density diet to improve insulin sensibility and thus reduce the risk of sarcopenia. Regular physical activity is also strongly recommended.

In common with other omics technologies, mass spectrometry (MS)-based proteomics produces ever-increasing amounts of raw data, making efficient analysis a principal challenge. A plethora of different computational tools can process the MS data to derive peptide and protein identification and quantification. However, during the last years there has been dramatic progress in computer science, including collaboration tools that have transformed research and industry. To leverage these advances, we develop AlphaPept, a Python-based open-source framework for efficient processing of large high-resolution MS data sets. Numba for just-in-time compilation on CPU and GPU achieves hundred-fold speed improvements. AlphaPept uses the Python scientific stack of highly optimized packages, reducing the code base to domain-specific tasks while accessing the latest advances. We provide an easy on-ramp for community contributions through the concept of literate programming, implemented in Jupyter Notebooks. Large datasets can rapidly be processed as shown by the analysis of hundreds of proteomes in minutes per file, many-fold faster than acquisition. AlphaPept can be used to build automated processing pipelines with web-serving functionality and compatibility with downstream analysis tools. It provides easy access via one-click installation, a modular Python library for advanced users, and via an open GitHub repository for developers., (© 2024. The Author(s).)

Single-cell proteomics by mass spectrometry is emerging as a powerful and unbiased method for the characterization of biological heterogeneity. So far, it has been limited to cultured cells, whereas an expansion of the method to complex tissues would greatly enhance biological insights. Here we describe single-cell Deep Visual Proteomics (scDVP), a technology that integrates high-content imaging, laser microdissection and multiplexed mass spectrometry. scDVP resolves the context-dependent, spatial proteome of murine hepatocytes at a current depth of 1,700 proteins from a cell slice. Half of the proteome was differentially regulated in a spatial manner, with protein levels changing dramatically in proximity to the central vein. We applied machine learning to proteome classes and images, which subsequently inferred the spatial proteome from imaging data alone. scDVP is applicable to healthy and diseased tissues and complements other spatial proteomics and spatial omics technologies., (© 2023. The Author(s).)

Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput, and robustness, which we address here by a streamlined multiplexed workflow using data-independent acquisition (mDIA). We demonstrate automated and complete dimethyl labeling of bulk or single-cell samples, without losing proteomic depth. Lys-N digestion enables five-plex quantification at MS1 and MS2 level. Because the multiplexed channels are quantitatively isolated from each other, mDIA accommodates a reference channel that does not interfere with the target channels. Our algorithm RefQuant takes advantage of this and confidently quantifies twice as many proteins per single cell compared to our previous work (Brunner et al, PMID 35226415), while our workflow currently allows routine analysis of 80 single cells per day. Finally, we combined mDIA with spatial proteomics to increase the throughput of Deep Visual Proteomics seven-fold for microdissection and four-fold for MS analysis. Applying this to primary cutaneous melanoma, we discovered proteomic signatures of cells within distinct tumor microenvironments, showcasing its potential for precision oncology., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Recent advances in mass spectrometry-based proteomics enable the acquisition of increasingly large datasets within relatively short times, which exposes bottlenecks in the bioinformatics pipeline. Although peptide identification is already scalable, most label-free quantification (LFQ) algorithms scale quadratic or cubic with the sample numbers, which may even preclude the analysis of large-scale data. Here we introduce directLFQ, a ratio-based approach for sample normalization and the calculation of protein intensities. It estimates quantities via aligning samples and ion traces by shifting them on top of each other in logarithmic space. Importantly, directLFQ scales linearly with the number of samples, allowing analyses of large studies to finish in minutes instead of days or months. We quantify 10,000 proteomes in 10 min and 100,000 proteomes in less than 2 h, a 1000-fold faster than some implementations of the popular LFQ algorithm MaxLFQ. In-depth characterization of directLFQ reveals excellent normalization properties and benchmark results, comparing favorably to MaxLFQ for both data-dependent acquisition and data-independent acquisition. In addition, directLFQ provides normalized peptide intensity estimates for peptide-level comparisons. It is an important part of an overall quantitative proteomic pipeline that also needs to include high sensitive statistical analysis leading to proteoform resolution. Available as an open-source Python package and a graphical user interface with a one-click installer, it can be used in the AlphaPept ecosystem as well as downstream of most common computational proteomics pipelines., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Abdominal vascular injuries are associated with significant morbidity and mortality. Treatment options include non-operative management, open repair, and endovascular procedures. This study aimed to characterize patients and detail treatment modalities among those who sustained a traumatic abdominal vascular injury., Methods: A six-year descriptive retrospective study was conducted at a level 1 trauma center and included all adult patients who sustained an abdominal vascular injury. Data abstracted included demographics, admitting characteristics, mechanism of injury, admitting vitals, injury details, diagnostic and treatment information, hospital course, and follow-up data., Results: Fifty-seven patients were admitted with abdominal vascular injuries, however, 14 patients sustained injuries to smaller vascular branches and were excluded. Most vascular injuries involved the iliac artery (27.9%, n = 12), abdominal aorta (25.6%, n = 11), and inferior vena cava (25.6%, n = 11). Twenty-seven percent (n = 12) of patients sustained an injury to more than one vascular structure. Thirty-four percent of patients (n = 15) died before treatment of the abdominal vascular injury. Among the 28 patients (65.1%) treated for their vascular injuries, 46.4% (n = 13) were treated with open surgery, 32.1% (n = 9) were treated non-operatively, and 21.4% (n = 6) with coil embolization. Sixty-four percent of the patients (n = 18) who survived to discharge presented for follow-up care with a mean follow-up period of 3 ± 4.1 months. There were no vascular reinterventions after discharge for patients who followed up with our hospital., Conclusions: Study findings suggested that appropriately selected cases of traumatic vascular injuries may be managed non-operatively and safely, as there were no mortalities, complications, or reinterventions among these patients., (© 2023 The University of Kansas Medical Center.)

Bacteria reorganize their physiology upon entry to stationary phase. What part of this reorganization improves starvation survival is a difficult question because the change in physiology includes a global reorganization of the proteome, envelope, and metabolism of the cell. In this work, we used several trade-offs between fast growth and long survival to statistically score over 2,000 Escherichia coli proteins for their global correlation with death rate. The combined ranking allowed us to narrow down the set of proteins that positively correlate with survival and validate the causal role of a subset of proteins. Remarkably, we found that important survival genes are related to the cell envelope, i.e., periplasm and outer membrane, because the maintenance of envelope integrity of E. coli plays a crucial role during starvation. Our results uncover a new protective feature of the outer membrane that adds to the growing evidence that the outer membrane is not only a barrier that prevents abiotic substances from reaching the cytoplasm but also essential for bacterial proliferation and survival., (©2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Machine learning and in particular deep learning (DL) are increasingly important in mass spectrometry (MS)-based proteomics. Recent DL models can predict the retention time, ion mobility and fragment intensities of a peptide just from the amino acid sequence with good accuracy. However, DL is a very rapidly developing field with new neural network architectures frequently appearing, which are challenging to incorporate for proteomics researchers. Here we introduce AlphaPeptDeep, a modular Python framework built on the PyTorch DL library that learns and predicts the properties of peptides ( https://github.com/MannLabs/alphapeptdeep ). It features a model shop that enables non-specialists to create models in just a few lines of code. AlphaPeptDeep represents post-translational modifications in a generic manner, even if only the chemical composition is known. Extensive use of transfer learning obviates the need for large data sets to refine models for particular experimental conditions. The AlphaPeptDeep models for predicting retention time, collisional cross sections and fragment intensities are at least on par with existing tools. Additional sequence-based properties can also be predicted by AlphaPeptDeep, as demonstrated with a HLA peptide prediction model to improve HLA peptide identification for data-independent acquisition ( https://github.com/MannLabs/PeptDeep-HLA )., (© 2022. The Author(s).)

Background: Amino acid metabolism is crucial for inflammatory processes during atherogenesis. The endogenous amino acid homoarginine is a robust biomarker for cardiovascular outcome and mortality with high levels being protective. However, the underlying mechanisms remain elusive. We investigated the effect of homoarginine supplementation on atherosclerotic plaque development with a particular focus on inflammation., Methods: Female ApoE-deficient mice were supplemented with homoarginine (14 mg/L) in drinking water starting 2 weeks before and continuing throughout a 6-week period of Western-type diet feeding. Control mice received normal drinking water. Immunohistochemistry and flow cytometry were used for plaque- and immunological phenotyping. T cells were characterized using mass spectrometry-based proteomics, by functional in vitro approaches, for example, proliferation and migration/chemotaxis assays as well as by super-resolution microscopy., Results: Homoarginine supplementation led to a 2-fold increase in circulating homoarginine concentrations. Homoarginine-treated mice exhibited reduced atherosclerosis in the aortic root and brachiocephalic trunk. A substantial decrease in CD3 + T cells in the atherosclerotic lesions suggested a T-cell-related effect of homoarginine supplementation, which was mainly attributed to CD4 + T cells. Macrophages, dendritic cells, and B cells were not affected. CD4 + T-cell proteomics and subsequent pathway analysis together with in vitro studies demonstrated that homoarginine profoundly modulated the spatial organization of the T-cell actin cytoskeleton and increased filopodia formation via inhibition of Myh9 (myosin heavy chain 9). Further mechanistic studies revealed an inhibition of T-cell proliferation as well as a striking impairment of the migratory capacities of T cells in response to relevant chemokines by homoarginine, all of which likely contribute to its atheroprotective effects., Conclusions: Our study unravels a novel mechanism by which the amino acid homoarginine reduces atherosclerosis, establishing that homoarginine modulates the T-cell cytoskeleton and thereby mitigates T-cell functions important during atherogenesis. These findings provide a molecular explanation for the beneficial effects of homoarginine in atherosclerotic cardiovascular disease.

Single-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable-core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease., (© 2022 The Authors Published under the terms of the CC BY 4.0 license.)

Purpose: This study examined the safety and efficacy of placing both a central venous dialysis catheter and a central venous catheter for infusion in the right internal jugular vein compared to only a central venous dialysis catheter., Methods: We conducted a retrospective chart review for all adult patients who underwent the placement of the right internal jugular dialysis catheter by a single surgeon. Patients were grouped based on whether they received a tunneled dual lumen dialysis catheter alone or in combination with a central venous infusion catheter in the right internal jugular vein. Catheter-related thrombosis, line infections, line malfunctions, pneumothorax, and need for line replacement were evaluated., Results: There were 97 patients in the dialysis catheter and central venous infusion line group and 63 patients in the dialysis catheter only group. The two groups were not different with regard to age (62.1 ± 16.3 years vs 57.9 ± 17.6 years) and gender (47.4% male vs 55.6% male). No significant differences were found in the incidence of thrombosis (1.0 % vs 0.0%, p  > 0.999), line infection (2.1% vs 0.0%, p  = 0.519), or line malfunctions (2.1% vs 0.0%, p  = 0.516) in patients who did or did not have a central venous infusion catheter placed concomitantly with the dialysis catheter, respectively. No patients in either group had a pneumothorax., Conclusions: Although not currently utilized with frequency, these preliminary data indicate that placing both a dual lumen dialysis catheter and central venous infusion catheter in the right internal jugular simultaneously could be a viable option.

The current study highlights a novel bio-sorbent design based on polyelectrolyte multi-layers (PEM) biopolymeric material. First layer was composed of sodium alginate and the second was constituted of citric acid and k-carrageenan. The PEM system was crosslinked to non-woven cellulosic textile material. Resulting materials were characterized using FT-IR, SEM, and thermal analysis (TGA and DTA). FT-IR analysis confirmed chemical interconnection of PEM bio-sorbent system. SEM features indicated that the microspaces between fibers were filled with layers of functionalizing polymers. PEM exhibited higher surface roughness compared to virgin sample. This modification of the surface morphology confirmed the stability and the effectiveness of the grafting method. Virgin cellulosic sample decomposed at 370 °C. However, PEM samples decomposed at 250 °C and 370 °C, which were attributed to the thermal decomposition of crosslinked sodium alginate and k-carrageenan and cellulose, respectively. The bio-sorbent performances were evaluated under different experimental conditions including pH, time, temperature, and initial dye concentration. The maximum adsorbed amounts of methylene blue are 124.4 mg/g and 522.4 mg/g for the untreated and grafted materials, respectively. The improvement in dye sorption evidenced the grafting of carboxylate and sulfonate groups onto cellulose surface. Adsorption process complied well with pseudo-first-order and Langmuir equations.

The adsorption phenomenon using low-cost adsorbents that are abundant in nature is of great interest when the adsorbed capacity is significant. A newly designed natural polyelectrolyte multi-layered (PEM) biopolymeric system-based chitosan/modified chitosan polymer and functionalized cellulosic nonwoven material was prepared and used as an effective adsorbent for Reactive Red 198 (RR198) dye solutions. The bio-sorbent was characterized by FTIR, SEM, and thermal (TGA/DTA) analysis. The swelling behavior was also evaluated, showing the great increase of the hydrophilicity of the prepared adsorbent biopolymer. The effect of various process parameters on the performance of RR198 dye removal such as pH, contact time, temperature, and initial dye concentration was studied. The biopolymeric system has shown good efficiency of adsorption compared to other adsorbents based on chitosan polymer. The highest adsorption capacity was found to be 722.3 mgg -1 at pH = 4 (ambient temperature, time = 120 min and dye concentration = 600 mg L -1 ). The adsorption process fitted well to both pseudo-second-order kinetics and Freundlich/Temkin adsorption isotherm models. Regarding its low cost, easy preparation, and promising efficient adsorption results, this new concepted multi-layered bio-sorbent could be an effective solution for the treatment of industrial wastewater.

In this work, powdered Calotropis gigantea seedpods were characterized and used as biosorbents of methylene blue dye from aqueous solution. FT-IR spectroscopy demonstrated functional groups characteristics of cellulose. Steric exclusion chromatography donated an average molecular weight of 230 kg/mol of the biopolymer. The polymolecularity index value (1.95) proved the good homogeneity of the polysaccharide. Scanning electron microscopy features displayed a homogenous morphology and porous structure. X-ray diffraction patterns showed peaks characteristics of cellulose and non-cellulose compositions. Thermogravimetric analysis/differential thermal analysis displayed exothermal decompositions at 316.9 °C and 456 °C. The maximum biosorption capacity of methylene blue was 88.36 mg/g at pH = 6, time = 60 min, and T = 21 °C. The level was comparable to some other studied agricultural wastes. The adsorption mechanism followed pseudo-second-order and Freundlich models. As it is abundant, available, low-cost, and easily recovered from solution, C. gigantea seedpods could be used as an effective biomaterial for the removal of organic pollutants from contaminated waters. Novelty statement: An abundant, available, and low-cost Calotropis gigantea seedpod was used, for the first time, as an effective biomaterial for the biosorption of organic pollutants. The biosorption level was found to be comparable to some other agricultural wastes studied previously in the literature.

Background: Various hematological malignancies, including multiple myeloma, plasmacytoma, aggressive lymphoma, and indolent lymphoma, rarely result in spinal cord compression., Methods: Here, we retrospectively analyzed 32 patients with multiple myeloma (50%), plasmacytoma (13%), aggressive lymphoma (28%), and indolent lymphoma (9%), resulting in spinal cord compression (2004 and 2016). Patients averaged 57 years of age and presented with the indolent onset of spinal cord compression (91% of cases) resulting mostly in motor deficits (69%)., Results: Local treatment modalities included radiotherapy (RT) (28%) alone, decompressive surgery (28%) alone, or decompressive surgery with consolidation RT (40%). The 1-year overall survival was 70%, and the progression-free survival frequency was 62%., Conclusion: This study highlighted the importance of standardizing the indications for RT alone versus RT with surgery depending on the patient's underlying pathological diagnosis, neurological deficits, and radiological findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Objective: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock., Methods: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment., Results: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m 2 /cm 5 and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m 2 /cm 5 . A statistically significant correlation was found between echocardiography and transpulmonary thermodilution ( r =0.86, 95% confidence interval (CI) 0.74, 0.93; P <0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was -111.95 dynes.s.m 2 /cm 5 (95% CI -230.06, 6.16). Limits of agreement were -785.86, 561.96., Conclusions: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.

Mass spectrometry based proteomics is the method of choice for quantifying genome-wide differential changes of protein expression in a wide range of biological and biomedical applications. Protein expression changes need to be reliably derived from many measured peptide intensities and their corresponding peptide fold changes. These peptide fold changes vary considerably for a given protein. Numerous instrumental setups aim to reduce this variability, whereas current computational methods only implicitly account for this problem. We introduce a new method, MS-EmpiRe, which explicitly accounts for the noise underlying peptide fold changes. We derive data set-specific, intensity-dependent empirical error fold change distributions, which are used for individual weighing of peptide fold changes to detect differentially expressed proteins (DEPs).In a recently published proteome-wide benchmarking data set, MS-EmpiRe doubles the number of correctly identified DEPs at an estimated FDR cutoff compared with state-of-the-art tools. We additionally confirm the superior performance of MS-EmpiRe on simulated data. MS-EmpiRe requires only peptide intensities mapped to proteins and, thus, can be applied to any common quantitative proteomics setup. We apply our method to diverse MS data sets and observe consistent increases in sensitivity with more than 1000 additional significant proteins in deep data sets, including a clinical study over multiple patients. At the same time, we observe that even the proteins classified as most insignificant by other methods but significant by MS-EmpiRe show very clear regulation on the peptide intensity level. MS-EmpiRe provides rapid processing (< 2 min for 6 LC-MS/MS runs (3 h gradients)) and is publicly available under github.com/zimmerlab/MS-EmpiRe with a manual including examples., (© 2019 Ammar et al.)

To break down organismal fitness into molecular contributions, costs and benefits of cellular components must be analyzed in all phases of the organism's life cycle. Here, we establish the required quantitative approach for the death phase of the model bacterium Escherichia coli. We show that in carbon starvation, an exponential decay of viability emerges as a collective phenomenon, with viable cells recycling nutrients from cell carcasses to maintain viability. The observed collective death rate is determined by the maintenance rate of viable cells and the amount of nutrients recovered from dead cells. Using this relation, we study the cost of a wasteful enzyme during starvation and the benefit of the stress response sigma factor RpoS. While the enzyme increases maintenance and thereby the death rate, RpoS improves biomass recycling, decreasing the death rate. Our approach thus enables quantitative analyses of how cellular components affect the survival of non-growing cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment., Aim: To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF., Methods: Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines., Results: The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67-83%), 61% (95% CI: 52-70%), and 70% (95% CI: 61-79%) (P=0.008). Changes in prevalence were significant between admission and discharge (P=0.0018). Despite a similar ID prevalence at admission and 1 month (P=0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ=0.30; P=0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month., Conclusions: Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome., Methods: A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib., Results: 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m 2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants., Conclusions: This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring., Competing Interests: Competing interests: JC received received modest consultant and lecture fees from MSD, Janssen, Merck, Novartis, Astra-Zeneca. FT received grants from Fédération Francaise de Cardiologie, Ministère français de la Santé, Fondation Coeur et Recherche, Ligue contre le Cancer, Assistance Publique – Hôpitaux de Marseille, Vifor Pharma. FT exercised an expert activity with Institut Nationale du Cancer. FT received personal fees for lectures and speakers bureaus from Abbott, Novartis, Amgen, Janssen-Cilag, Merck Sharp and Dohme, Bristol-Myers Squibb, Pfizer, Roche, Vifor Pharma, Sanofi, Astra-Zeneca. FT received non-financial support for travel and lunch paid from Abbott, Novartis, Amgen, Janssen-Cilag, Merck Sharp and Dohme, Bristol-Myers Squibb, Pfizer, Roche, Vifor Pharma, Sanofi, Astra-Zeneca, Servier, Sorin, Boston Scientific, Actelion, Bayer, Biotronik, Boehinger Ingelheim, The Medecines Compagny, Orion Pharma, Correvio, Daiichi Sankyo, St Jude Medical, Lilly, Zoll Medical, LivaNova, Medtronic, Sorin, Philips, Genzyme, Icomed, Leo Pharma, Mylan Medical, Preciphar, Resmed. AC received modest consultant and lecture fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, and Sanofi-Aventis.Stephane Ederhy received modest consultant and lecture fees from Lilly, Daiichy-Sankyo, Celgene, Pfizer, Esperare, Bristol-Myers Squibb, Janssen, Philips Healthcare, Bayer, Novartis, Amgen, Ipsen.

Spectral libraries play a central role in the analysis of data-independent-acquisition (DIA) proteomics experiments. A main assumption in current spectral library tools is that a single characteristic intensity pattern (CIP) suffices to describe the fragmentation of a peptide in a particular charge state (peptide charge pair). However, we find that this is often not the case. We carry out a systematic evaluation of spectral variability over public repositories and in-house data sets. We show that spectral variability is widespread and partly occurs under fixed experimental conditions. Using clustering of preprocessed spectra, we derive a limited number of multiple characteristic intensity patterns (MCIPs) for each peptide charge pair, which allow almost complete coverage of our heterogeneous data set without affecting the false discovery rate. We show that a MCIP library derived from public repositories performs in most cases similar to a "custom-made" spectral library, which has been acquired under identical experimental conditions as the query spectra. We apply the MCIP approach to a DIA data set and observe a significant increase in peptide recognition. We propose the MCIP approach as an easy-to-implement addition to current spectral library search engines and as a new way to utilize the data stored in spectral repositories.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To report a successful method of managing an embolized Edwards SAPIEN XT aortic valve prosthesis using a thoracic endovascular aortic repair rescue., Case Report: An 84-year-old man underwent transcatheter aortic valve replacement using a 26-mm Edwards SAPIEN XT valve, which immediately embolized into the ascending aorta. Because of the severe tapering of the patient's transverse aortic arch, the embolized valve was unable to be maneuvered further down the aorta. Therefore, a Cook 36×80-mm Zenith Dissection Endovascular System (ZDES) bare metal stent was used on a compassionate basis to append the embolized valve between the patient's coronary artery ostia and the innominate artery takeoff within the ascending aorta, with no neurological or cardiovascular complications at 12-month follow-up., Conclusion: A Cook ZDES bare metal stent may be successfully used to append an embolized Edwards SAPIEN XT valve within the ascending aorta., (© The Author(s) 2015.)

Aim: To determine the demographic, clinical, biological and bacteriological profile of acute community acquired hematogenous osteomyelitis (AHO) in children., Methods: Prospective study including children admitted for AHO. We noted the demographic parameters of patients and the clinical, biological and radiological characteristics of the infection. Blood cultures and local specimen in operated children were systematically performed., Results: 70 patients were included. The mean age was 7.7 years. The mean time between onset of symptoms and admission was 3.2 days. Distal tibia was the most frequent localization (18.66%). Fever higher than 38° on admission was found in 92.8% of patients. Creactive protein (CRP) was superior to 20 mg / L in 95.8% and ESR superior to 20 mm in the first hour in 92% of cases. A deep venous thrombosis was found in 7 patients and a pleuropulmonary Staphylococcus infection in 4 patients. A micro organism was isolated in 64.7% of cases. Staphylococcus aureus methicillin susceptible (SAMS) was the predominant germ. Staphylococcus aureus methicillin resistant (SAMR) accounted for 15.7% of staphylococcus aureus infections. The importance of CRP on admission and time to resolution of fever after the start of treatment were significantly higher in SAMR infections. The existence of deep venous thrombosis and a pleuropulmonary Staphylococcus infection and the need for surgical drainage were significantly more frequent in SAMR infections., Conclusion: The existence of a severe form of AHO should lead to a high suspicion of SAMR infection and prompt the prescription of an appropriate antibiotiotherapy.

Treatment of rigid and severe spinal deformities is challenging and risky. Preoperative halo-gravity traction can be used to progressively reduce the deformity before spinal fusion. The aim of this study was to evaluate the effectiveness of halo-gravity traction for the correction of severe spinal deformities. Fifteen patients were reviewed retrospectively. Their mean age at the beginning of traction was 13.5 years. The mean duration of traction was 64 days. The main curve in the coronal plane improved from +/- 95 degrees to +/- 67 degrees, a gain of +/- 28 degrees (range 0 degrees-50 degrees) or +/- 30%. The curve in the sagittal plane improved from +/- 96 degrees to +/- 78 degrees, a gain of +/- 18 degrees (range 0 degrees-45 degrees) or +/- 19%. Other authors report gains up to 46% and 43%, respectively in the coronal and in the sagittal plane, but this might be due to different conditions, techniques, and evaluations. One patient with a pre-existing neurological deficit developed paraplegia. According to the literature congenital curves with associated kyphosis are exposed to paraplegia. Halo-gravity traction is effective and is usually tolerated better than other techniques of traction using the halo device.

The purpose of this study is to evaluate the early results of the Ponseti method and the effectiveness of the Steenbek foot abduction brace. A total of 74 patients with 110 idiopathic clubfeet were included in this prospective study. The feet were evaluated according to the Dimeglio-Bensahel classification, the Catteral-Pirani classification and the functional classification of the Hospital for Joint Diseases. Ninety-eight feet (89%) had a good result after the casting period. All the feet evaluated after the period of full-time bracing and during the period of part-time bracing showed a good correction. The Ponseti method using the Steenbek foot abduction brace is effective in correcting idiopathic clubfeet.