Altered expression of cytokines, chemokines, growth factors, and soluble receptors in patients with colorectal cancer, and correlation with treatment outcome.

Insofar as they play an important role in the pathogenesis of colorectal cancer (CRC), this study analyzes the serum profile of cytokines, chemokines, growth factors, and soluble receptors in patients with CRC and cancer-free controls as possible CRC signatures. Serum levels of 65 analytes were measured in patients with CRC and age- and sex-matched cancer-free controls using the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Of the 65 tested analytes, 8 cytokines (CSF-3, IFN-γ, IL-12p70, IL-18, IL-20, MIF, TNF-α and TSLP), 8 chemokines (fractalkine, MIP-1ß, BLC, Eotaxin-1, Eotaxin-2, IP-10, MIP-1a, MIP-3a), 2 growth factors (FGF-2, MMP-1), and 4 soluble receptors (APRIL, CD30, TNFRII, and TWEAK), were differentially expressed in CRC. ROC analysis confirmed the high association of TNF-α, BLC, Eotaxin-1, APRIL, and Tweak with AUC > 0.70, suggesting theranostic application. The expression of IFN-γ, IL-18, MIF, BLC, Eotaxin-1, Eotaxin-2, IP-10, and MMP1 was lower in metastatic compared to non-metastatic CRC; only AUC of MIF and MIP-1ß were > 0.7. Moreover, MDC, IL-7, MIF, IL-21, and TNF-α are positively associated with tolerance to CRC chemotherapy (CT) (AUC > 0.7), whereas IL-31, Fractalkine, Eotaxin-1, and Eotaxin-2 were positively associated with resistance to CT. TNF-α, BLC, Eotaxin-1, APRIL, and Tweak may be used as first-line early detection of CRC. The variable levels of MIF and MIP-1ß between metastatic and non-metastatic cases assign prognostic nature to these factors in CRC progression. Regarding tolerance to CT, MDC, IL-7, MIF, IL-21, and TNF-α are key when down-regulated or resistant to treatment is observed.

Novel approach to analysis of the immune system using an ungated model of immune surface marker abundance to predict health outcomes.

Traditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a new way of looking at immune data, which is by looking directly at the values of the surface markers without dividing the cells into different subtypes. To assess the merit of this approach, we compared it with manual gating using cytometry data from the Singapore Longitudinal Aging Study (SLAS) database. We used two different neural networks (one for each method) to predict the presence of several health conditions. We found that the model built using raw surface marker abundance outperformed the manual gating one and we were able to identify some markers that contributed more to the predictions. This study is intended as a brief proof-of-concept and was not designed to predict health outcomes in an applied setting; nonetheless, it demonstrates that alternative methods to understand the structure of immune variation hold substantial progress.

CT iterative reconstruction algorithms: a task-based image quality assessment.

PURPOSE: To assess the dose performance in terms of image quality of filtered back projection (FBP) and two generations of iterative reconstruction (IR) algorithms developed by the most common CT vendors. MATERIALS AND METHODS: We used four CT systems equipped with a hybrid/statistical IR (H/SIR) and a full/partial/advanced model-based IR (MBIR) algorithms. Acquisitions were performed on an ACR phantom at five dose levels. Raw data were reconstructed using a standard soft tissue kernel for FBP and one iterative level of the two IR algorithm generations. The noise power spectrum (NPS) and the task-based transfer function (TTF) were computed. A detectability index (d') was computed to model the detection task of a large mass in the liver (large feature; 120 HU and 25-mm diameter) and a small calcification (small feature; 500 HU and 1.5-mm diameter). RESULTS: With H/SIR, the highest values of d' for both features were found for Siemens, then for Canon and the lowest values for Philips and GE. For the large feature, potential dose reductions with MBIR compared with H/SIR were - 35% for GE, - 62% for Philips, and - 13% for Siemens; for the small feature, corresponding reductions were - 45%, - 78%, and - 14%, respectively. With the Canon system, a potential dose reduction of - 32% was observed only for the small feature with MBIR compared with the H/SIR algorithm. For the large feature, the dose increased by 100%. CONCLUSION: This multivendor comparison of several versions of IR algorithms allowed to compare the different evolution within each vendor. The use of d' is highly adapted and robust for an optimization process. KEY POINTS: • The performance of four CT systems was evaluated by using imQuest software to assess noise characteristic, spatial resolution, and lesion detection. • Two task functions were defined to model the detection task of a large mass in the liver and a small calcification. • The advantage of task-based image quality assessment for radiologists is that it does not include only complicated metrics, but also clinically meaningful image quality.

Optimization of radiation dose for CT detection of lytic and sclerotic bone lesions: a phantom study.

OBJECTIVES: To determine the best compromise between low radiation dose and suitable image quality for the detection of lytic and sclerotic bone lesions of the lumbar spine and pelvis. METHODS: A phantom was scanned using the routine protocol (STD, 13 mGy) and six decreasing dose levels. Raw data were reconstructed using level 3 of iterative reconstruction (IR3) with 1-mm slice thickness for the STD protocol and highest IR levels with 3-mm slice thickness for the others. CTDIvol was used for radiation dose assessment. Quantitative criteria (noise power spectrum [NPS], task-based transfer function [TTF], and the detectability index [d']), as well as qualitative analysis, were used to compare protocols. NPS and TTF were computed using specific software (imQuest). d' was computed for two imaging tasks: lytic and sclerotic bone lesions. A subjective analysis was performed to validate the image quality obtained on the anthropomorphic phantom with the different dose values. RESULTS: Similar d' values were found for CTDIvol from 3 to 4 mGy with IR4 and from 1 to 2 mGy for IR5 compared with d' values using the STD protocol. Image quality was validated subjectively for IR4 but rejected for IR5 (image smoothing). Finally, for the same d', the dose was reduced by 74% compared with the STD protocol, with the CTDIvol being 3.4 mGy for the lumbar spine and for the pelvis. CONCLUSION: A dose level as low as 3.4 mGy, in association with high levels of IR, provides suitable image quality for the detection of lytic and sclerotic bone lesions of the lumbar spine and pelvis. KEY POINTS: • A CTDI volof 3.4 mGy, in association with high iterative reconstruction level, provides suitable image quality for the detection of lytic and sclerotic bone lesions, both at objective and subjective analysis. • Compared with the standard protocol, radiation dose can be reduced up to 74% for the lumbar spine and pelvis. • A task-based image quality assessment using  the detectability index represents an objective method for the assessment of image quality and bridges the gap between complex physical metrics and subjective image analysis.

Correction to: Patient dose reference levels in surgery: a multicenter study.

The original version of this article, published on 01 August 2018, unfortunately contained two mistakes.

Patient dose reference levels in surgery: a multicenter study.

OBJECTIVE: To assess diagnostic reference levels (DRLs) in surgery for the most frequent procedures as required by the European Directive 2013/59/Euratom. METHODS: A survey was conducted in six centers. Eight orthopedic, urology and gastrointestinal surgical procedures were analyzed. Kerma area product (KAP) and fluoroscopy time (FT) were recorded for 50 patients (except for elbow: 30 patients) per procedure and per center from September 2016 to September 2017. DRLs were calculated as the 3rd quartiles of the distributions. For shoulder surgery, DRLs were defined according to the complexity of the procedure. For hand/wrist and foot/ankle surgery, DRLs were defined according to the technology (conventional C-arm vs. mini-C-arm). RESULTS: Results of 1870 procedures were retrieved. DRLs were calculated for the two dosimetric indicators and the eight procedures. DRLs were 2130 mGy.cm2 and 1.4 min for proximal femoral intramedullary nail, 1185 mGy.cm2 and 0.9 min for laparoscopic cholecystectomy and 2195 mGy.cm2 and 1.0 min for double-J (pigtail) ureteral catheter insertion. For shoulder surgery, KAP and FT were significantly higher (p < 0.05) for intramedullary procedures compared to extramedullary procedures. For hand/wrist and foot/ankle surgery, the KAPs were significantly higher (p < 0.05) with conventional C-arm compared to mini-C-arm, but FTs were not significantly different (p: not significant). CONCLUSION: This study reports DRLs in surgery based on a multicentric survey. KEY POINTS: • Delivered dose in surgery depends on procedure, practice and patient. • Diagnostic reference levels (DRLs) are proposed for eight surgical procedures. • DRLs are useful to benchmark practices and optimize protocols.

Intracellular signalling pathways: targets to reverse immunosenescence.

Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem.

From inflamm-aging to immune-paralysis: a slippery slope during aging for immune-adaptation.

Aging is accompanied by many physiological changes including those in the immune system. These changes are designated as immunosenescence indicating that age induces a decrease in immune functions. However, since many years we know that some aspects are not decreasing but instead are increasing like the pro-inflammatory activity by the innate immune cells, especially by monocytes/macrophages. Recently it became evident that these cells may possess a sort of memory called trained memory sustained by epigenetic changes occurring long after even in the absence of the initiator aggressor. In this review we are reviewing evidences that such changes may occur in aging and describe the relationship between inflamm-aging and immunosenescence as an adaptation/remodelling process leading on one hand to increased inflammation and on the other to decreased immune response (immune-paralysis) mastered by the innate immune system. These changes may collectively induce a state of alertness which assure an immune response even if ultimately resulting in age-related deleterious inflammatory diseases.

Vertebral sarcoidosis: long-term follow-up with MRI.

Vertebral involvement in sarcoidosis is rare and its clinical and imaging features are non-specific. Indeed, because the lesions are hard to differentiate from metastatic disease based on imaging alone, a histological confirmation is advised. Fatty replacement is a well-known finding indicating stabilization and healing in both benign and malignant conditions. It can be used as an indicator of a favorable disease course and response to treatment. We report the case of a 43-year-old woman with multifocal vertebral sarcoidosis lesions and long-term follow-up showing progressive and gradual fatty involution on magnetic resonance imaging (MRI) during 4 years of steroid treatment with a final favorable outcome.

A predictive score for the result of carbapenem-resistant Enterobacterales and vancomycin-resistant enterococci screening.

BACKGROUND: The duration of extensively drug-resistant bacteria (XDR) carriage depends on several factors for which the information can be difficult to recover. AIM: To determine whether past screening and clinical results of patients can predict the results of subsequent screening. METHODS: In total, 256 patients were retrospectively included from 10 healthcare centres in France from January 2014 to January 2022. We created a predictive clearance score, ranging from -5 to +7, that included the number of XDR species and the type of resistance detected in the sample, as well as the time from the last positive sample, the number of previous consecutive negative samples, and obtaining at least one negative PCR result in the collection. This score could be used for the upcoming rectal screening of a patient carrying an XDR as soon as the last screening sample was negative. FINDINGS: The negative predictive value was >99% for score ≤0. The median time to achieve XDR clearance was significantly shorter for a score of 0 (443 days (259-705)) than that based on previously published criteria. CONCLUSION: This predictive score shows high performance for the assessment of XDR clearance. Relative to previous guidelines, it could help to lift specific infection prevention and control measures earlier. Nevertheless, the decision should be made according to other factors, such as antimicrobial use and adherence to hand hygiene.

MRI for response assessment in metastatic bone disease.

BACKGROUND: Beyond lesion detection and characterisation, and disease staging, the quantification of the tumour load and assessment of response to treatment are daily expectations in oncology. METHODS: Bone lesions have been considered "non-measurable" for years as opposed to lesions involving soft tissues and "solid" organs like the lungs or liver, for which response evaluation criteria are used in every day practice. This is due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques available for bone assessment, i.e. skeletal scintigraphy (SS), radiographs and computed tomography (CT). RESULTS: This paper reviews the possibilities and limitations of these techniques and highlights the possibilities of positron emission tomography (PET), but mainly concentrates on magnetic resonance imaging (MRI). CONCLUSION: Practical morphological and quantitative approaches are proposed to evaluate the treatment response of bone marrow lesions using "anatomical" MRI. Recent developments of MRI, i.e. dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered. KEY POINTS: • MRI offers improved evaluation of skeletal metastases and their response to treatment. • This new indication for MRI has wide potential impact on radiological practice. • MRI helps meet the expectations of the oncological community. • We emphasise the practical aspects, with didactic cases and illustrations.

Immunology of Aging: the Birth of Inflammaging.

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

The role of elastin peptides in modulating the immune response in aging and age-related diseases.

It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.

Mechanical behavior and corrosion resistance of sol-gel derived 45S5 bioactive glass coating on Ti6Al4V synthesized by electrophoretic deposition.

The purpose of this work is the synthesis and the characterization of sol-gel derived 45S5 bioactive glass coatings deposited onto Ti6Al4V alloy substrates. This coating aims the improvement of the biocompatibility of metallic implants for use in dentistry and orthopedy. The 45S5 bioactive glass powder was synthetized by the sol-gel process and the coatings were produced by the electrophoretic deposition technique (EPD). A grinding protocol was developed to reduce the particle size distribution of the sol-gel powder in order to obtain a stable suspension needed for the electrophoretic deposition. The particle size distribution of the sol-gel powder was determined using Dynamic Light Scattering (DLS). Different characterization techniques including X-ray diffraction (XRD), Scanning electron microscopy (SEM) associated to X-ray microanalysis (EDXS), were used to investigate the microstructure and the morphology of the coatings before and after an optimized thermal treatment. Homogeneous 45S5 bioactive glass coatings were obtained with no observable defects. However these coatings are functional if they present good mechanical properties. Thus, a mechanical study using nano-indentation and micro-scratch testing was carried out. The obtained results showed that well adherent and cohesive coatings were obtained. The Young's modulus and the hardness are improved with the thermal treatment. Indeed, they increased from 11 ± 0.54 GPa and 100 ± 4.34 MPa respectively to 28 ± 1.34 GPa and 300 ± 14.21 MPa. The corrosion resistance of the coatings was also studied. The electrochemical were carried using a Potentiostat-Galvanostat PGZ301 in 3.5% NaCl solution at 37 °C. It was observed that the 45S5 sol-gel derived bioactive glass coatings allowed the enhancement of corrosion resistance of the implant.

Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

Aging, frailty and age-related diseases.

The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive.

Alterations in the immune system with aging are considered to underlie many age-related diseases. However, many elderly individuals remain healthy until even a very advanced age. There is also an increase in numbers of centenarians and their apparent fitness. We should therefore change our unilaterally detrimental consideration of age-related immune changes. Recent data taking into consideration the immunobiography concept may allow for meaningful distinctions among various aging trajectories. This implies that the aging immune system has a homeodynamic characteristic balanced between adaptive and maladaptive aspects. The survival and health of an individual depends from the equilibrium of this balance. In this article, we highlight which parts of the aging of the immune system may be considered adaptive in contrast to those that may be maladaptive.

Impact of ultra-low dose CT acquisition on semi-automated RECIST tool in the evaluation of malignant focal liver lesions.

PURPOSE: To compare the evaluation of malignant focal liver lesions (FLLs) using a semi-automated RECIST tool with a standard and an ultra-low dose (ULD) computed tomography (CT) protocol. MATERIALS AND METHODS: Thirty-four patients with malignant FLLs underwent two abdominal-pelvic CT examinations one using a standard protocol and one using an ULD protocol. There were 23 men and 11 women with a mean age 64.3±14.4 (SD) years (range: 22-91 years). Dosimetric indicators were recorded, and effective dose was calculated for both examinations. Mean malignant FLL attenuation, image noise and contrast-to-noise-ratio (CNR) were compared. The largest malignant FLL per patient was evaluated using the semi-automated RECIST tool to determine longest axis length, longest orthogonal axis length, volume and World Health Organisation area. RESULTS: Dosimetric values were significantly reduced by -56% with ULD compared to standard protocol. No differences in mean malignant FLL attenuation values were found between the two protocols. Image noise was significantly increased for all locations (P<0.05) with ULD compared to standard protocol, and CNR was significantly reduced (P<0.05). On the 34 malignant FLLs analyzed, six semi-automated shapes non-concordant with radiologist's visual impression were highlighted with the software, including one FLL (1/34; 3%) with standard CT acquisition only, three FLLs (3/34; 9%) with ULD CT acquisition only and two FLLs (2/34; 6%) with both CT acquisitions. After manual editing, the concordance of the values of the studied criteria between both acquisitions was good and no significant difference was reported. CONCLUSION: Semi-automated RECIST tool demonstrates good performances using ULD CT protocol. It could be used in routine clinical practice with a ULD protocol for follow-up studies in patients with known malignant FLL.

PICC management led by technicians: Establishment of a cooperation program with radiologists and evaluation of complications.

PURPOSE: The purpose of this study was to evaluate a cooperation program in order to compare incidence of complications after peripherally inserted central catheter (PICC) placement between radiologists and technicians. MATERIALS AND METHODS: PICC placement technique was standardized with ultrasound-guided puncture and fluoroscopic guidance. Numbers of PICC delegated to technicians, and PICC placement difficulties, were prospectively recorded for the whole study population whereas complications such as PICC infection, deep venous thrombosis and catheter occlusion were prospectively recorded until PICC removal for a subgroup of patients included during one month. RESULTS: A total of 722 patients had PICC placement. There were 382 men and 340 women with a mean age of 66.8±15.8 (SD) years (range: 18-94years); of these, 442/722 patients (61.22%) were included in the cooperation program with 433/722 patients (59.97%) who effectively had PICC placement by technicians and 289/722 (40.03%) by radiologists. Technicians needed radiologists' help for 23/442 patients (5.20%) including 6 failed PICC placement subsequently performed by radiologists. Twenty complications (20/77; 26%) were recorded in the subgroup of 77 patients studied for complications. No differences in complications rate were found between the 33 patients who underwent PICC placement by radiologists (6/33; 18%) and the 44 patients who underwent PICC placement by technicians (14/44; 32%) (P=0.296). Complications included 8 PICC-related infections (8/77; 10.4%), 3 deep venous thromboses (3/77; 3.9%) and 9 catheter occlusions (9/77; 11.7%). CONCLUSION: PICC placement led by technicians is feasible and safe without statistical difference in terms of complications compared to PICC placement made by radiologists.

Asymptomatic carriage of extensively drug-resistant bacteria (eXDR), a simple way to assess spontaneous clearance.

The duration of eXDR carriage depends on several factors that might be difficult to recover. We aim to assess the duration of eXDR carriage by using a simple to recover parameter: the number of consecutive negative screening. 131 eXDR carriers (51 VRE and 80 CPE) were included. The number of consecutive negative screenings was strongly associated with eXDR clearance. All patients displaying at least three negative screenings over a seven-month period were never screened positive thereafter. Taking into account the number of negative screenings as a part of a case-by-case risk assessment would be helpful for the decision to maintain or lift eXDR-focused precautions.