Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50.

INTRODUCTION: Pembrolizumab alone (IO-mono) or in combination with platinum-based chemotherapy (CT-IO) is first-line standard of care for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. This retrospective multicentre study assessed real-world use and efficacy of both strategies. METHODS: Patients with advanced NSCLC PD-L1 ≥ 50% from eight hospitals who had received at least one cycle of IO-mono or CT-IO were included. Overall survival (OS) and real-word progression-free-survival were estimated using Kaplan-Meier methodology. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, and a Cox model with inverse propensity treatment weighting was carried out. RESULTS: Among the 243 patients included, 141 (58%) received IO-mono and 102 (42%) CT-IO. Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. With a median follow-up of 11.5 months (95% CI 10.4-13.3), median OS was not reached, but no difference was observed between groups (p = 0.51). Early deaths at 12 weeks were 11% (95% CI 4.6-16.9) and 15.2% (95% CI 9.0-20.9) in CT-IO and IO groups (p = 0.32). After adjustment for age, gender, performance status, histology, brain metastases, liver metastases and tobacco status, no statistically significant difference was found for OS between groups, neither in the multivariate adjusted model [HR 1.07 (95% CI 0.61-1.86), p = 0.8] nor in propensity adjusted analysis [HR 0.99 (95% CI 0.60-1.65), p = 0.99]. Male gender (HR 2.01, p = 0.01) and PS ≥ 2 (HR 3.28, p < 0.001) were found to be negative independent predictive factors for OS. CONCLUSION: Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. However, sparing the chemotherapy in first-line does not appear to impact survival outcomes, even regarding early deaths.

Hypothermia - an unusual initial presentation of human immunodeficiency virus infection.

We report an unusual case of human immunodeficiency virus (HIV) infection initially presenting with hypothermia and bradycardia associated with an HIV encephalitis. Searches reveal only five reported cases of spontaneous episodic hypothermia in the context of HIV infection. In our case, magnetic resonance imaging revealed the presence of a persistent cavum septum pellucidum (CSP), an anatomical and functional neuro-developmental abnormality, as well as changes compatible with an HIV encephalitis. Episodic hypothermia can occur in association with agenesis of the corpus callosum, known as Shapiro's syndrome, and the presence of a persistent CSP in our case suggests it may have contributed to the clinical presentation.

Management of drooling in children with cerebral palsy: A French survey.

AIM: To characterise children with cerebral palsy (CP) and pathological drooling in France, and to describe care pathways, assessment and treatment. METHOD: A transversal, observational, descriptive survey of the practices and opinions of 400 health professionals potentially involved in the care of children with CP, was carried out nationally across France in 2013. RESULTS: The response rate was 36%. Seventy-five questionnaires were returned and analysed (52%). A small proportion of children were specifically treated for drooling (<25%). Assessments were carried out in 75% of cases and 91% of professionals prescribed treatments. Use of assessment tools varied widely. The most common treatment was oro-facial rehabilitation (95% of professionals), followed by anticholinergic drugs (Scopolamine(®)) (94%) botulinum toxin injections (BT) (66%) and surgery (34%). Scopolamine was considered to be less effective than BT and to have more side effects. CONCLUSION: The rate of pathological drooling in children with CP is likely underestimated and under treated in France. There is a lack of knowledge regarding assessment tools. Aside from rehabilitation, current practice is to prescribe medication as the first-line treatment, however professionals consider that BT is more effective and has less side effects.

[Exercise therapy in the treatment of idiopathic adolescent scoliosis: Is it useful?]. / La kinésithérapie dans le traitement de la scoliose idiopathique de l'adolescent : utile ou pas ?

Many practitioners, pediatricians, and general practitioners prescribe physical therapy when tracking scoliosis. However, has physical therapy alone proved its efficacy in the care of the scoliosis to slow down progression? Our purpose is to report the results of a literature review on the effectiveness of rehabilitation in idiopathic scoliosis. No current study presents sufficient scientific proof to validate the efficacy of isolated exercise therapy in scoliosis. Learned societies recognize, however, the efficacy of combining conservative therapy (brace+physiotherapy) in idiopathic scoliosis. Should we then still prescribe rehabilitation without brace treatment? Although physical therapy alone does not seem effective in treating scoliosis, it can limit potential painful phenomena and be beneficial for respiratory function. The physical therapist can also teach the teenager the classic principles of hygiene of the back. It may therefore be appropriate to prescribe physical therapy, but the principles and objectives must be explained to the patient and family in light of current evidence-based medicine.

Pulse oximetry screening for critical congenital heart disease in the neonatal intensive care unit.

OBJECTIVE: Pulse oximetry screening (POS) is an effective tool to detect critical congenital heart disease (CCHD) in asymptomatic term infants, but its value in the neonatal intensive care unit (NICU) requires further clarification. STUDY DESIGN: A retrospective review of 1005 babies without previously diagnosed CCHD admitted to a level III NICU was performed to assess the risk for missed CCHD and performance of POS. RESULT: Of the 1005 NICU patients, 812 had documented POS and none failed POS. In 812 patients, 547 had delayed POS because of the use of supplemental oxygen. In 259/812 patients, POS was delayed until the baby was >2 weeks old. CCHD was excluded by echocardiography, irrespective of POS, in 287/1005 patients. CONCLUSION: POS can be performed in the NICU with minimal adverse effects. However, in many NICU patients CCHD is confirmed or excluded before POS, and POS will frequently be performed after CCHD would have been expected to become symptomatic.

Acute mastoiditis--the role of radiology.

Acute mastoiditis is a commonly occurring condition in children and adults, and one that most radiologists will come across at some point during their on-call duties. Acute mastoiditis is usually clinically apparent. However, the complications, especially the intracranial ones, can be more insidious and may have fatal consequences. Therefore, it is imperative that the radiologist is well versed in identifying these. Local spread of infection from the mastoids and middle ear cleft may occur via four routes: bone erosion, thrombophlebitis, periphlebitis, and via the anatomical pathways. The role of radiology is largely to demonstrate the complications of mastoiditis, which can be clinically occult and are often serious; this article will highlight these complications.

Heterogeneous cell mechanical properties: an atomic force microscopy study.

Atomic force microscopy (AFM) is a non-invasive microscopy to explore living biological systems like cells in liquid environment. Thus AFM is an appropriate tool to investigate surface chemical modification and its influence on biological systems. In particular, control over biomaterial surface chemistry can result in a regulated cell response. This report investigates the influence of adhesive and non-adhesive surfaces on the cell morphology and the influence of the cytoskeleton structure on the local mechanical properties. In this study, the main work concerns a thorough investigation of the height images obtained with an AFM as therecorded images provide the evolution of the mechanical properties of the cell as function of its local structure. Information on the cell elasticity due to the cytoskeleton organization is deduced when comparing the AFM tip indentation depth versus the distance between the cytoskeleton bundles for the different samples.

Characterization of dynamic cellular adhesion of osteoblasts using atomic force microscopy.

BACKGROUND: Atomic force microscopy (AFM) can be used to visualize the cell morphology in an aqueous environment and in real time. It also allows the investigation of mechanical properties such as cell compliance as a function of cell attachment. This study characterized and evaluated osteoblast adhesion by AFM. METHODS: Human bone marrow stromal cells were cultured on two types of surface to induce weak and strong cellular adhesions. RESULTS: Cells were considered as spreading if they had a flattened and lengthened shape and a cytoskeletal organization in the submembrane cytosolic region. Cell detachment demonstrated different adhesion states between adherent cells to be distinguished. The stability of the cytoskeletal fibers indicated that cells were adherent. The elastic modulus was estimated by two complementary approaches. The values deduced were between 3 x 10(2) and 2 x 10(5) Nm(-2) according to the state of cell adhesion and the approaches used to measure this elastic modulus. CONCLUSIONS: Although the results were qualitative, a relation may be deduced between the elasticity of living cells as demonstrated by cytoskeletal organization and the state of cell adhesion. The technique could be used to determine the adhesion state of an adherent osteoblast observed under AFM.

Study of two grafting methods for obtaining a 3-aminopropyltriethoxysilane monolayer on silica surface.

In order to establish a 3-aminopropyltriethoxysilane (APTES) grafting procedure with limited number of APTESs noncovalently linked to the silica surface, two different methods of grafting (in acid-aqueous solution and in anhydrous solution) were compared. The grafted surface state was investigated by atomic force microscopy (AFM). The stability of the grafting was checked at different temperatures by AFM. Continuous and plane APTES grafted surfaces were successfully prepared using both grafting preparations. The grafting in an anhydrous solution behaves homogeneously and stably compared to the grafting in an acid-aqueous solution. Moreover, with anhydrous solution, results showed that a unique monolayer of APTES was grafted.

Ti4+ to Ti3+ conversion of TiO2 uppermost layer by low-temperature vacuum annealing: interest for titanium biomedical applications.

Because of the Ti(3+) defects responsibility for dissociative adsorption of water onto TiO(2) surfaces and due to the hydroxyls influence on the biological behavior of titanium, controlling the Ti(3+) surface defects density by means of low-temperature vacuum annealing is proposed to improve the bone/implant interactions. Experiments have been carried out on Ti-6Al-4V alloys exhibiting a porous surface generated primarily by chemical treatment. XPS investigations have shown that low-temperature vacuum annealing can create a controlled number of Ti(3+) defects (up to 21% Ti(3+)/Ti(4+) at 573 K). High Ti(3+) defect concentration is linked to surface porosity. Such surfaces, exhibiting high hydrophilicity and microporosity, would confer to titanium biomaterials a great ability to interact with surrounding proteins and cells and hence would favor the bone anchorage of as-treated implants.

Chemical, biochemical and cellular responses in the digestive gland of the mussel Mytilus galloprovincialis from the Spanish Mediterranean coast.

Mussels (Mytilus galloprovincialis) were sampled in March 1996 from five stations along the Western Mediterranean coast (Barcelona, Ebro Delta, Alboraya, Cullera, Denia) corresponding to urban, industrial and agricultural areas. Different biochemical and cellular markers were determined in the mussels in order to assess the effects and/or exposure to pollutants. The cytochrome P450 system, acetylcholinesterase and metallothioneins were among the biochemical markers selected for the study. Histochemical analysis of ß-glucuronidase and catalase activity were performed as marker enzymes for lysosomes and peroxisomes. Chemical analyses indicated that mussels from Barcelona and Denia as highly exposed to polycyclic aromatic hydrocarbons (PAHs)(1.8-2.7 µg g(-1) w.w. against 0.02-0.10 µg g(-1) w.w.), and polychlorinated biphenyls (PCBs)(132-260 ng g(-1) w.w. against 8-24 ng g(-1) w.w.). This was in agreement with changes in lysosome structure and higher number of peroxisomes in those organisms. High levels of metals (particularly Cr and Cu) were recorded in the digestive gland of Alboraya mussels, which also had elevated metallothionein content (28 nmol g(-1) w.w.) in comparison with the other stations (15-20 nmol g(-1) w.w.). Benzo(a)pyrene hydroxylase (BPH) activity indicated Cullera and Barcelona as possibly polluted sites. The results support the usefulness of the biomarker approach to assess and diagnose environmental pollution. The use of a battery of biomarkers at different levels of biological organization coupled with chemical analysis is highlighted.

Limitations of ultrasound evaluation in acute closed renal trauma.

Imaging of the kidneys following acute closed renal trauma may be undertaken using one of several available modalities. Ultrasound evaluation is often the first choice of imaging modality, as it is quick, non-invasive and often readily available for urgent assessment. We report three cases in which significant under-evaluation of major renal parenchymal injury occurred using B-mode ultrasound; the injury was detected only by subsequent computerized tomography (CT) imaging.

[Amplified chemical disasters: a challenge for public health]. / Acidentes químicos ampliados: um desafio para a saúde pública.

Chemical accidents involving explosions, large fires and leakages of hazardous substances occurring during transport, storage and industrial production of chemicals constitute a real challenge to health, environmental and industrial safety professionals. The aim of this article is to discuss the main questions that this kind of accident provokes, in terms of public health, particularly in developing countries such as Brazil. The paper defines and characterises these accidents and the various health risk they involve excluding the leakages of hazardous substances during "normal" production in industry--through the combination of quantitative and qualitative information drawn from the international literature on the subject. From some examples of chemical accidents such as occurred in Bhopal (India), Vila Socó (Brazil), São Paulo (México) and data of the World Health Organization (WHO), the authors seek to show that these events present a worsening, in terms of immediate deaths and injuries, in developing countries. The statistics of chemical accidents which occurred during the last ten years (1984 to 1993) in the State of Rio de Janeiro are used taken as a frame reference for the purpose of bringing to light the great number of occurrences made with no registration of basic information regarding assessment or surveillance. The complexity of causes and consequences, together with the structural problems of developing countries, present public health professionals and institutions, with some important tasks especially those of health risk assessment and the formulation of strategies to prevent and control future major chemical accidents.

[Atemporality, history, and semiophysics]. / Atemporalité, histoire et sémiophysique.

The atemporality of the unconscious was a temporary term, used by Freud between 1911 and 1920. His definition was the result of consideration of energy, upon which it is intrinsically dependent. This is one of the contradictions that the term bears; other contradictioins depend upon its correlation to the elaboration of the concept of transfer, of its relationship with the existence of the principle of pleasure and with that of the dynamic point of view. But, atemporality is one of the terms with which Freud designated the tension between the reference to classical science and the morphological and morphogenetical point of view to which he, little by little, gave precedence, while he was forming metapsychology. The term disappeared after the introduction of the life and death urges, which would subsume the meanings introduced by atemporality. It is qualitative dynamics and semiophysics, to the extent that they reconsider the limits that classical science had placed on the concept of time, that allow for a new reading of the Freudian elaboration. They provide the possibility of stylizing the notion of time that Freud requires and they show the accuracy of his intuitions, beyond the manifest contradictions. The history of psychoanalysis could find herein some methodological elements.