Line-field confocal optical coherence tomography for actinic keratosis and squamous cell carcinoma: a descriptive study.

BACKGROUND: Early and accurate diagnosis of cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) is fundamental to reduce their associated morbidity and to select the correct treatment. Line-field confocal optical coherence tomography (LC-OCT) is a new imaging device that can characterize healthy skin and basal cell carcinoma, but no large studies on keratinocyte cell tumours have yet been published. AIM: To identify and describe LC-OCT criteria associated with SCC and AK, and to compare LC-OCT findings in these tumours. METHODS: A retrospective observational multicentre study was conducted. Lesions were imaged with the LC-OCT device before surgery and examined histologically. LC-OCT criteria for AK/SCC were identified and their presence was evaluated in all study lesions. Univariate and multivariate analyses were performed to compare AK and SCCs, and to investigate differences between in situ and invasive tumours. RESULTS: In total, 158 patients with 50 AK and 108 SCCs (62 in situ and 46 invasive) were included. Cytological and architectural alterations were found in most lesions, and differences were found between AK and SCCs. Although the visualization of the dermoepidermal junction (DEJ) was often hampered by hyperkeratosis and acanthosis, an outlined DEJ without broad strands was observed in almost all AK and almost all in situ SCCs, but in only three invasive SCCs (P < 0.001) when the DEJ was detectable. CONCLUSION: Our results suggest that LC-OCT can help clinicians in the identification of AK and SCC and their differentiation, providing a real-time and noninvasive examination. Further studies are needed to confirm our data.

Patients with atherosclerotic peripheral arterial disease have a high risk of lung cancer: Systematic review and meta-analysis of literature.

PURPOSE: Lung cancer and atherosclerosis share common risk factors. Literature data suggest that the prevalence of lung malignancy in patients with peripheral arterial disease (PAD) is higher than in the general population. Our goal was to determine, through a systematic literature review, the prevalence of lung cancer in patients with PAD. METHODS: We consulted available publications in the Cochrane library, MEDLINE, PUBMED, EMBASE, and ClinicalTrials.gov. We included all articles, written in English or French, published between 1990 and 2020 reporting the prevalence of lung cancer in patients with PAD (atherosclerotic aortic aneurysm or peripheral occlusive diseases). Patients with coronary artery disease, cardiac valvulopathy or carotid stenosis were not included. We did not include case reports. We performed a critical analysis of each article. Data were collected from two independent readers. A fixed effect model meta-analysis allowed to estimate a summary prevalence rate. RESULTS: We identified 303 articles, and selected 19 articles according to selection criteria. A total of 16849 patients were included (mean age 68.3 years, 75.1% of males). Aortic aneurysms were found in 29% of patients and atherosclerotic occlusive disease in 66% of patients. Lung cancer was identified in 538 patients, representing a prevalence of 3%. DISCUSSION: Lung cancer is found in 3% of patients with atherosclerotic PAD. This prevalence is higher than that found in lung cancer screening programs performed in the general population of smokers and former smokers. These patients should be screened for lung cancer. Their selection may dramatically increase the benefit of lung cancer screening.

Line-field confocal optical coherence tomography of basal cell carcinoma: a descriptive study.

BACKGROUND: Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line-field confocal optical coherence tomography (LC-OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT. OBJECTIVES: To identify and describe LC-OCT criteria associated with BCC and explore their association with BCC subtypes. METHODS: Basal cell carcinoma were imaged with a handheld LC-OCT device before surgical excision. LC-OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes. RESULTS: Eighty-nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC-OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules. CONCLUSIONS: This was the first study describing the characteristics of BCC under LC-OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses.

Raman imaging as a new analytical tool for the quality control of the monitoring of osteogenic differentiation in forming 3D bone tissue.

In this study, adipose-derived stem cells (ASCs) are used to produce 3D bone grafts. The safety and the feasibility of using these bone grafts have been already showed and quality controls are already implemented. However, a cheaper, fast and non-destructive technique is required to monitor the osteogenic differentiation process. Here, the use of Raman imaging to monitor the synthesis of the extracellular matrix and its progressive mineralization occurring during the osteogenic differentiation process is investigated for the first time on a 3D in forming bone tissue. The attention was focused on Raman bands related to this matrix belonging to phosphate, phenylalanine and hydroxyproline, which are very distinctive and intense. The kinetic of the osteogenic differentiation process was first compared between a 2D and a 3D forming bone tissue. It was observed that the kinetics of the osteogenic differentiation process is slower in 3D in forming bone tissue. In a second step, an evaluation of the reliability of the Raman imaging method was performed including a study of the influence of the harvest biopsies position on the forming 3D bone tissue. The repeatability and the specificity of this method were also demonstrated. In a last step, several batches of ASCs were cultured and analyzed in 3D at different time points using Raman imaging. From the mean Raman spectra, mineral to matrix ratios (MTMR) were determined and used to evaluate the formation of mineral deposits accompanying the extracellular matrix synthesis which is indicative of an ongoing osteogenic differentiation process. These ratios peaked between the day 35 and 49. This observation was very interesting since it corresponds to the time at which the 3D bone grafts are used for the patient surgery. To conclude, Raman imaging allowed fast acquisition and time-resolved monitoring in vitro of the mineralization of extracellular matrix during osteogenic differentiation.

Estimation of blood loss during adult burn surgery.

INTRODUCTION: Large burns excision and graft can produce major blood loss. The main objective of this study is to evaluate the blood loss in relation with the excision size in square centimeters (cm2) in adults. PATIENTS AND METHODS: We conducted a monocentric, observational, prospective and open study in a burn intensive care unit. Patients aged-over 18 with burn wounds excision and autografting covering at least 5% of total body surface area (TBS) were enrolled. Blood loss was evaluated with Mercuriali formula. RESULTS: 139 procedures were evaluated: median graft size was 1637cm2, median blood loss was 0.8ml/cm2 excised and grafted skin and median total blood loss was 1444ml. 84 procedures (i.e. 60.4%) required transfusion. 66 procedures concerned upper limbs, 75 lower limbs, 17 head and 72 trunk. 126 procedures used tangential excision, 10 used fascia excision and 3 used the two techniques. Patients with comorbidities (ASA score 3 or 4) had more bleeding (p=0.001). CONCLUSION: The results that were obtained, i.e. approximately 0.8ml/cm2 of excised and grafted skin, are similar to those of other published studies, which concerned specific populations such as pediatrics. Determining blood loss in one centre can help physicians to calculate the excisable area without any transfusion. However, blood loss can vary widely between patients and one must consider individual clinical situation to provide safe surgery.

Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

Patient characteristics influencing the variability of distributed parameter-based models in DCE-CT kinetic analysis.

Kinetic parameter variability may be sensitive to kinetic model choice, kinetic model implementation or patient-specific effects. The purpose of this study was to assess their impact on the variability of dynamic contrast-enhanced computed tomography (DCE-CT) kinetic parameters. A total of 11 canine patients with sinonasal tumours received high signal-to-noise ratio, test-double retest DCE-CT scans. The variability for three distributed parameter (DP)-based models was assessed by analysis of variance. Mixed-effects modelling evaluated patient-specific effects. Inter-model variability (CVinter ) was comparable to or lower than intra-model variability (CVintra ) for blood flow (CVinter :[4-28%], CVintra :[28-31%]), fractional vascular volume (CVinter :[3-17%], CVintra :[16-19%]) and permeability-surface area product (CVinter :[5-12%], CVintra :[14-15%]). The kinetic models were significantly (P<0.05) impacted by patient characteristics for patient size, area underneath the curve of the artery and of the tumour. In conclusion, DP-based models demonstrated good agreement with similar differences between models and scans. However, high variability in the kinetic parameters and their sensitivity to patient size may limit certain quantitative applications.

Acute pelvic pain in females in septic and aseptic contexts.

Acute pelvic pain in women is a common reason for emergency department admission. There is a broad range of possible aetiological diagnoses, with gynaecological and gastrointestinal causes being the most frequently encountered. Gynaecological causes include upper genital tract infection and three types of surgical emergency, namely ectopic pregnancy, adnexal torsion, and haemorrhagic ovarian cyst rupture. The main gastrointestinal cause is acute appendicitis, which is the primary differential diagnosis for acute pelvic pain of gynaecological origin. The process of diagnosis will be guided by the clinical examination, laboratory study results, and ultrasonography findings, with suprapubic transvaginal pelvic ultrasonography as the first-line examination in this young population, and potentially cross-sectional imaging findings (computed tomography and MR imaging) if diagnosis remains uncertain.

[Scleritis and episcleritis: diagnosis and treatment]. / Sclérites et épisclérites : prise en charge diagnostique et thérapeutique.

Episcleritis and scleritis are distinct entities with regard to visual prognosis, risk of associated systemic disease, and treatment. The pertinence of the clinical classification of episcleritis and scleritis established in 1976 still persists, with significant differences in terms of visual prognosis, associated general conditions, and therapeutic choices according to each scleritis subtype. Episcleritis requires rarely to be referred to a tertiary care centre, and if so it has to be monitored similarly to scleritis. In this paper, an analysis of 1358 scleritis cases from the main distinct large series published since 1976 shows a mean proportion of 8% of infectious aetiologies (mainly herpes viruses), and 28% of systemic diseases with two main subgroups: inflammatory rheumatisms 12.8%, and systemic vasculitis 7.8%. Overall, the risk for visual loss following scleritis is around 16%. However, the risks of associated systemic disease and visual loss are both highly variable according to the type of scleritis, and culminate at 80% and 50% in the necrotizing subtype respectively. As compared with older series, the proportion of necrotizing scleritis is lower in recent series which is likely due to the advances obtained over the past 20 years in immunomodulatory therapy, as well as its wide use in the treatment of the main systemic conditions associated with scleritis. The treatment of scleritis should be managed by physicians who are experts in the use of immunosuppressive drugs that may be required in one out of two affected patients.

[History of cancer and chemotherapy before chemotherapy]. / Histoire du cancer et de la chimiothérapie avant la chimiothérapie.

Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

[Feasibility of patient-injected anticoagulation therapy: the GRANTED experience]. / Faisabilité pratique de l'auto-injection des traitements anticoagulants: l'expérience du réseau GRANTED.

BACKGROUND: Injectable anticoagulation therapy is indicated for several months following diagnosis of venous thromboembolic disease (VTE) in a context of active neoplasia. Certain studies have shown an improvement in patient compliance using self-injections. PURPOSE: Allow patients to safely make their own injections of anticoagulants after checking their aptitude and motivation. METHODS: At the prescribing physician's request, the GRANTED network provided patients and/or the resource person with specific education and training. The educational program was proposed to patients with an indication for a treatment for at least 3 months. After becoming familiar with the injection material and its manipulation, the patient and/or resource person performed sham injections on test materials. Patients were then allowed to decide for themselves whether or not to participate in the self-injection protocol. The prescribing physician received a report from the training team. RESULTS: From November 2010 to July 2012, 39 patients participated in the educational program, generally in a context of vitamin K antagonist prescriptions. Sixteen of these patients had a neoplasia. The educational program corrected erroneous or imprecise points of information, particularly concerning syringe purging. DISCUSSION: The education program proved to be interesting for points other than those initially foreseen and allowed the team to rectify a certain number of erroneous messages unrecognized by the prescribing physicians. This result goes in line with the need for accompanying patients who have a prescription for self-injections and also emphasizes the need for careful follow-up.

Elaboration of highly hydrophobic polymeric surface--a potential strategy to reduce the adhesion of pathogenic bacteria?

Different polymeric surfaces have been modified in order to reach a high hydrophobic character, indeed the superhydrophobicity property. For this purpose, polypropylene and polystyrene have been treated by RF or µwaves CF4 plasma with different volumes, the results were compared according to the density of injected power. The effect of pretreatment such as mechanical abrasion or plasma activation was also studied. The modified surfaces were shown as hydrophobic, or even superhydrophobic depending of defects density. They were characterized by measurement of wettability and roughness at different scales, i.e. macroscopic, mesoscopic and atomic. It has been shown that a homogeneous surface at the macroscopic scale could be heterogeneous at lower mesoscopic scale. This was associated with the crystallinity of the material. The bioadhesion tests were performed with Gram positive and negative pathogenic strains: Listeria monocytogenes, Pseudomonas aeruginosa and Hafnia alvei. They have demonstrated an antibacterial efficiency of very hydrophobic and amorphous PS treated for all strains tested and a strain-dependent efficiency with modified PP surface being very heterogeneous at the mesoscopic scale. Thus, these biological results pointed out not only the respective role of the surface chemistry and topography in bacterial adhesion, but also the dependence on the peaks and valley distribution at bacteria dimension scale.

Strain-specific pathogenicity of putative host-adapted and nonadapted strains of Streptococcus uberis in dairy cattle.

Streptococcus uberis is an important cause of intramammary infection in dairy cattle. Strains of Strep. uberis appear to differ in their ability to cause disease based on previous epidemiological studies. We explored the pathogenicity of 2 strains of Strep. uberis, where one strain represented a putatively host-adapted type based on its ability to cause persistent infection and to spread from cow to cow in a lactating herd. This type was part of a clonal complex that is commonly associated with bovine mastitis. The other strain, which was isolated from a transient infection in a single animal in the same herd and did not belong to any known clonal complex, was selected as putatively nonadapted type. Cows (6 per strain) were experimentally challenged in a single hind quarter and the adjacent hind quarter was used as mock challenged control quarter. Both strains showed an equal ability to grow in the milk of challenge animals in vitro. All cows that were challenged with the putatively host-adapted strain developed clinical signs of mastitis, including fever and milk yield depression as well as elevated somatic cell count due to influx of polymorphonuclear leucocytes and lymphocytes. The cytokine response followed a specific order, with an increase in IL-1ß, IL-6, and IL-8 levels at the time of first SCC elevation, followed by an increase in IL-10, IL-12p40, and tumor necrosis factor-α levels approximately 6h later. In 4 of 6 animals, IL-17A was detected in milk between 57 and 168 h postchallenge. The increase in IL-17A levels coincided with inversion of the prechallenge CD4(+)-to-CD8(+) T lymphocyte ratio, which was observed from 96 h postchallenge. This was followed by normalization of the CD4(+)-to-CD8(+) ratio due to continued increase of the CD8(+) concentration up to 312 h postchallenge. Spontaneous resolution of infection was observed in 5 animals and coincided with a measurable IL-17A response in 4 animals, suggesting that IL-17 may be involved in the resolution of intramammary infection. With the exception of minor elevation of IL-8 levels, no clinical, cytological, or immunological response was detected in quarters challenged with the nonadapted strain. The observed strain-specific pathogenicity was consistent across animals, implying that it is determined by pathogen factors rather than host factors.

[Severe bronchospasm using Diprivan® in a patient allergic to peanut and birch]. / Bronchospasme sévère au Diprivan® chez un enfant allergique à l'arachide et au pollen de bouleau.

Diprivan® is composed of propofol, refined soybean oil and purified egg phosphatide. One must eliminate any allergy to one of its components before use. We report the story of a child who underwent nevus surgery under general anesthesia which was associated with an hypersensitivity reaction. In fact, this child had asthma and allergy to peanuts, raising the problem of cross allergy between birch, peanut, soy and Diprivan®.

[Burn: An inflammatory process]. / La brûlure : une pathologie inflammatoire.

Thermal injury induce a two-phase inflammatory response: first, a pro-inflammatory status, resulting in a systemic inflammatory response syndrome, then an anti-inflammatory phase characterized by a profound defect in cellular-mediated immunity. This inflammatory reaction proceeds from complex phenomenons in whom many cellular elements are involved (macrophage is the central one) and very complex molecular products interact (especially cytokines). These phenomenons promote significant physiopathologic consequences, especially on cardiovascular homeostasis and endothelial permeability, that lower the prognosis. The inflammatory reaction can be modified, enhanced or maintained by adverse events (i.e. infection) resulting in degradation of clinical situation. Despite a better comprehension of the phenomenons underlying this inflammatory process, diagnosis or therapeutic applications are at that time disappointing.

TSG-6 protein expression in the pancreatic islets of NOD mice.

The histologic hallmark of the development of type 1 diabetes (T1D) is insulitis, characterized by leukocytic infiltration of the pancreatic islets. The molecules controlling the early influx of leukocytes into the islets are poorly understood. Tumor necrosis factor alpha (TNFalpha)-stimulated gene 6 (TSG-6) is involved in inflammation, extracellular matrix formation, cell migration, and development. In the present study, we examined the expression and cellular localization of TSG-6 protein in islets of female non-obese diabetic (NOD) mice using frozen section immunofluorescence staining. Pancreata from nondiabetic (8 and 25 weeks old), prediabetic (230-280 mg/dl blood glucose) and diabetic (>300 mg/dl blood glucose) NOD mice were stained for TSG-6, insulin, CD3, CD11c, Mac3 and CD31. TSG-6 protein was detected in 67% of islets of prediabetic mice, 27% of islets of 25-week old nondiabetic mice, and less than 7% of islets of diabetic mice and 8-week old nondiabetic mice. Lastly, islet-derived TSG-6 protein was localized to the infiltrating CD3 and CD11c positive leukocytes.

Adhesion of Staphylococcus aureus and Staphylococcus epidermidis to the Episkin reconstructed epidermis model and to an inert 304 stainless steel substrate.

AIMS: The aim of this study was to evaluate the respective influence of the physicochemical interactions and the roughness involved in the first part of the biological substrate biocontamination. METHODS AND RESULTS: Therefore we compared the bioadhesion results obtained on the biological model substrate (Episkin) and on a commonly employed inert substrate (AISI 304 stainless steel), frequently used either in dermatology or in development of medical devices. The two studied strains presented different characteristics, both physicochemical and microbiological. Staphylococcus epidermidis, a relatively hydrophobic bacteria capable of exchanging interactions which are principally of the van der Waals type, adhered more to 304 steel than to the surface of reconstituted skin. As for S. aureus, an essentially basic, hydrophilic bacteria, was more adherent to Episkin (a bipolar, hydrophilic substrate) than to stainless steel (a unipolar, basic, hydrophilic substrate). CONCLUSIONS: In the absence of electrostatic interactions, the adhesion of substrate-dependent bacteria to the surface of reconstituted skin was dependent upon the balance between gamma(LW), gamma(+) and gamma(-). SIGNIFICANCE AND IMPACT OF THE STUDY: Consequently, so as to restrict microbial adhesion and reduce adhesive binding between micro-organisms and the surface of the skin, it would be preferable to render this substrate hydrophobic and apolar through the use of appropriate surface treatment.

Two different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytes.

C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement system activation. C3a and C5a exert several biological activities through binding to their specific receptors, named C3aR and C5aR, respectively. We have previously shown that C3aR and C5aR are constitutively expressed by astrocytes, a cell type that actively participates in inflammatory events in the central nervous system. In this article, we focus on the transduction signal pathways activated by these two receptors on astrocytes. We show that the stimulation of C3aR or C5aR results in the activation of the mitogen activated protein kinase pathway by phosphorylation of the p44 and p42 kinases. On the contrary, the binding of C3a or C5a to their receptors on astrocytes decreases the production of cAMP, revealing an inhibition of the adenylyl cyclase pathway. Stimulation of C3aR and C5aR induces an increase in intracellular calcium concentration, arising from the opening of intracellular calcium channels. The observed calcium wave results from the activation of the phospholipase C pathway. Taken together, our results suggest that the binding of C3a or C5a to their receptors on astrocytes would be of functional importance since it induces the activation of two important transduction pathways leading to several cellular events such as neurotrophin and cytokine production.

C3A binds to the seven transmembrane anaphylatoxin receptor expressed by epithelial cells and triggers the production of IL-8.

The complement (C) plays an important role in many acute inflammatory processes. C3a is an inflammatory polypeptide named anaphylatoxin, generated during C activation and which acts through a specific receptor C3aR. In this study, we demonstrated that the epithelial cell line ECV 304 constitutively expressed C3aR (by flow cytometry and immunofluorescence) and that binding of purified C3a to epithelial cells resulted in a time- and dose-dependent upregulation of interleukin-8 (IL-8). Pre-treatment of ECV 304 with pertussis toxin inhibited IL-8 response induced by C3a, indicating that the action of C3a was mediated by a G protein coupled pathway.

Complement anaphylatoxin C3a is selectively protective against NMDA-induced neuronal cell death.

The anaphylatoxin C3a is a potent inflammatory polypeptide released at sites of complement activation. To test whether C3a might alter neuronal outcome following an ischemic insult, we determined the effects of purified human C3a on murine primary cortical cell cultures exposed to apoptotic or excitotoxic paradigms. C3a prevented neither serum deprivation-induced apoptotic neuronal death, nor AMPA/kainate-mediated excitotoxicity. However, in mixed cultures of neurons and astrocytes, C3a dose-dependently protected neurons against NMDA toxicity (47% neuroprotection using 100 nM C3a, p < 0.01, n = 12). The neuroprotective effect of C3a was observable only in the presence of astrocytes. These observations suggest that C3a is involved in excitotoxicity-mediated neuronal death through astrocyte stimulation and extend its role beyond immune functions.