Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Production of the bioinsecticide Bacillus thuringiensis subsp. israelensis with deltamethrin increases toxicity towards mosquito larvae.

UNLABELLED: Bacillus thuringiensis subsp. israelensis is a bioinsecticide used for larval mosquito control and it represents a safe alternative to chemical insecticides. Despite its environmental safety, it is less efficient and persistent than chemical insecticides. To bypass these limitations, we propose to combine the advantages of chemical and biological insecticides by producing Bti in a medium supplemented with a chemical insecticide (DDT, deltamethrin, permethrin, propoxur or temephos). Among the investigated insecticides, the addition of deltamethrin in the medium induced a higher toxicity (over 6.72-fold) of the composite deltamethrin-Bti towards mosquito larvae as compared to Bti alone. This was mainly due to the insertion of deltamethrin into the membranes of Bti spores, as evidenced by a quantification of membrane-extracted deltamethrin by HPLC. This composite larvicide is a promising tool to decrease the quantity of chemicals dispersed in the environment, to increase the efficacy of Bti and to facilitate its widespread use as a transition between chemical and biological insecticides. Further experiments are required to characterize the mechanisms that underline the incorporation of deltamethrin into Bti to optimize the production and the toxicity of this composite larvicide. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report of an increased efficacy of the mosquitocidal bioinsecticide Bacillus thuringiensis subsp. israelensis (Bti) when produced with a chemical insecticide. The results clearly demonstrate that deltamethrin is able to synergize the insecticidal activity of Bti through inclusion into spore membranes, reducing off-target and nonspecific toxicity occurring when the chemical is used alone as sprays. This new composite chemical-biological insecticide can become an invaluable tool as an intermediate between single chemical usage and the widespread use of Bti, notably in developing countries with limited financial resources for intensive mosquito control campaigns.

Hybrid polyoxometalates: Keggin and Dawson silyl derivatives as versatile platforms.

A new series of polyoxometalate-based hybrids has been synthesized. These covalently linked organic-inorganic materials represent valuable elementary building blocks ready for postfunctionalization, using classical organic reactions and couplings. This approach is exemplified by the grafting of an organic chromophore via a Sonogashira coupling.

[Indirect causes of maternal deaths (except stroke, cardiovascular diseases and infections) in France 2013-2015]. / Morts maternelles de causes indirectes (hors AVC, maladies cardiovasculaires et infections) en France 2013­2015.

Maternal deaths from indirect obstetric causes are the result of a pre-existing disease or condition that appeared during pregnancy without obstetric causes, but which was aggravated by the physiological effects of pregnancy. Twenty-six deaths from indirect causes related to a pre-existing pathology, excluding disease of the circulatory system or infection, were analysed by the committee of experts. Pre-existing pathology during pregnancy was documented in 13 women (asthma, n=3, genetic diseases, n=3, previous breast cancer, n=2, major sickle cell syndrome, n=2, epilepsy, n=1 and brain tumour, n=1). In 13 women, the pathology was not known before pregnancy (breast cancer, n=6, brain tumours, n=3, uterine sarcoma, n=1, cervical cancer, n=1, malignant melanoma, n=1 and acute myeloid leukaemia, n=1). For 16 women (61%), the death is related to a neoplastic pathology. Although the majority were considered inevitable for 11/16 women, 5 deaths were considered possibly preventable, the main preventable factor being a delay in diagnosis, and/or a delay in starting a specific treatment. For 10 women, the death is related to a chronic non-neoplastic pathology, known before pregnancy for 9 women, judged most often as possibly preventable, the main preventable factor being the failure of the medical team or the patient to take the pathology and/or its treatment into account. A preconception medical consultation with a specialist should be recommended to all patients with pre-existing disease. A clinical examination of the breasts is strongly recommended at the first visit and then during pregnancy.

[Maternal Deaths due to Amniotic Fluid Embolism in France 2013-2015]. / Mortalité maternelle par embolie amniotique en France 2013­2015.

Amniotic fluid embolism remains the 3rd cause of maternal death in France, with a stable rate and 28 deaths in this triennium, representing 10.7% of maternal deaths and a maternal mortality ratio of 1.2/100,000 live births. Cases are characterized by the suddenness of symptoms: the median delay between symptoms and death was 4h [0.75-696] with 20/28 patients did not reach the intensive care unit. Initial circulatory failure or cataclysmic haemorrhage was the two modes of presentation. Prodromes were reported in 17 (63%) cases and induction of labour was present in 12/27 (44%). One or more factors of sub-optimal care were present in 72% of the cases, and 52% of deaths were considered possibly or probably preventable. This preventability most often concerned the content of care but also the organisation of care (including human resources, communication, sites of care and referrals). The delay in establishing a well-conducted cardio-circulatory resuscitation or the delay in setting up an optimal transfusion strategy were the most frequent elements of substandard care. Absence or delay at hysterectomy during haemorrhagic situations was reported in 15/20 cases. The experts suggest being on the alert to diagnose amniotic embolism at an early stage, initiating intense resuscitation "outside the walls", envisaging a hysterectomy without delay if the haemorrhage is intense. On an organisational level, a "vital emergency maternity care" plan, specific to each establishment could be proposed.

Photochemical activation of an azido manganese-monosubstituted keggin polyoxometalate: on the road to a Mn(V)-nitrido derivative.

The manganese(V)-nitrido polyoxometalate derivative [PW(11)O(39){Mn(V)N}](5-) has been synthesized by photochemical activation of the parent manganese(III)-azido derivative [PW(11)O(39)Mn(III)N(3)](5-). It was characterized by mass spectrometry, (31)P NMR, UV-vis, and IR spectroscopies. An electrochemistry study indicated that only the Mn(V) state was stable. The photoactivation of the manganese(III)-azido derivative proceeds through two competitive routes, yielding to the targeted product of photooxidation {Mn(V)N} or the undesirable product of photoreduction {Mn(II)L} (L = H(2)O, N(3)), depending on the photolysis conditions. A simplified photolysis mechanism involving two different excited states was proposed to account for the temperature and wavelength dependence.

Charge transport through redox active [H7P8W48O184]33- polyoxometalates self-assembled onto gold surfaces and gold nanodots.

Polyoxometalates (POMs) are redox-active molecular oxides, which attract growing interest for their integration into nano-devices, such as high-density data storage non-volatile memories. In this work, we investigated the electrostatic deposition of the negatively charged [H7P8W48O184]33- POM onto positively charged 8-amino-1-octanethiol self-assembled monolayers (SAMs) preformed onto gold substrates or onto an array of gold nanodots. The ring-shaped [H7P8W48O184]33- POM was selected as an example of large POMs with high charge storage capacity. To avoid the formation of POM aggregates onto the substrates, which would introduce variability in the local electrical properties, special attention has to be paid to the preformed SAM seeding layer, which should itself be deprived of aggregates. Where necessary, rinsing steps were found to be crucial to eliminate these aggregates and to provide uniformly covered substrates for subsequent POM deposition and electrical characterizations. This especially holds for commercially available gold/glass substrates while these rinsing steps were not essential in the case of template stripped gold of very low roughness. Charge transport through the related molecular junctions and nanodot molecule junctions (NMJs) has been probed by conducting-AFM. We analyzed the current-voltage curves with different models: electron tunneling though the SAMs (Simmons model), transition voltage spectroscopy (TVS) method or molecular single energy level mediated transport (Landauer equation) and we discussed the energetics of the molecular junctions. We concluded to an energy level alignment of the alkyl spacer and POM lowest occupied molecular orbitals (LUMOs), probably due to dipolar effects.

Is Inhibitor of differentiation 3 involved in human primary Sjögren's syndrome?

OBJECTIVES: Inhibitor of differentiation 3 (Id3)-deficient mice show sicca symptoms, lymphocyte infiltration of exocrine glands and positive anti-Ro/SSA and anti-La/SSB antibodies, all hallmarks of primary Sjögren's syndrome (pSS). The impairment of Id3 in T cells and, possibly, in salivary glandular epithelial cells (SGECs) seems to be involved. This animal model prompted us to investigate the role of Id3 in human pSS. METHODS: Quantitative Id3 expression in peripheral T cells, cultured SGECs and in total minor salivary glands was assessed by RT-PCR in pSS patients and controls. After Id3 sequencing, we investigated two single nucleotide polymorphisms (SNPs) (c.313G>A and g.-156A>G) in a case-control study of 212 Caucasian pSS patients and 168 controls. RESULTS: Quantitative Id3 expression was not decreased in pSS patients nor in SGECs, in T cells or in minor salivary glands. As well, patients and controls did not differ in allele and genotype frequencies of Id3 SNPs (P = 0.67 and P = 0.71 for the c.313G>A and the g.-156A>G, respectively). Neither SNP was associated with a pattern of autoantibody secretion. CONCLUSION: Although the Id3-deficient mouse model represents an attractive model for human pSS, Id3 expression is not impaired in SGECs, peripheral T cells and in labial salivary glands in pSS patients and Id3-relevant SNPs do not give evidence of genetic predisposition in Caucasian pSS patients.

[Maternal deaths due to amniotic fluid embolism. Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Mortalité maternelle par embolie amniotique. Résultats de l'ENCMM, France 2010­2012.

Amniotic fluid embolism (AFE) is an unpredictable, dreadful complication of pregnancy or childbirth. EA typically includes in the same lapse of time respiratory, haemodynamic, neurological and hemorrhagic symptoms (from early and severe coagulopathy). Immediate supportive treatment by a multidisciplinary team is the cornerstone of the management. Between 2010 an 2012 in France, 24 deaths were related to AFE giving a maternal mortality ratio of 1/100,000 live births (CI 95% 0.6-1.4). AFE ranks as the second leading cause of direct maternal death. Eight cases over 23 were classified as having some degree of substandard care. Substandard care included delays in performing aggressive surgical treatment or delays in the diagnosis and the treatment of the coagulopathy. Learning points focus on the importance to pay attention on premonitory symptoms, to early assess the clotting status and to train in multidisciplinary team.

[Indirect causes of maternal deaths (except stroke, cardiovascular diseases and infections): Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Morts maternelles de causes indirectes (hors AVC, maladies cardiovasculaires et infections) : résultats de l'ENCMM, France 2010­2012.

Maternal deaths of indirect causes result of a preexisting disease or an affection appeared during the pregnancy without any relationship with obstetrical causes, but worsened by the physiological effects of pregnancy. Among the 23 deaths of indirect cause related to a preexisiting pathology, 22 (96 %) have been analyzed by the expert comity. A known or preexisting chronic disease was documented in 16 patients (sick-cell disorder, n=3, treated epilepsy, n=3, intracerebral carvenomas, n=1, multifocal glial tumor, n=1, breast cancer, n=1, systemic lupus, n=1, diabetes mellitus, n=3, antiphospholipid syndrome, n=1). For 6 women, the pathology was unknown before the pregnancy (glioblastoma, n=2, epilepsy, n=1, Ehlers-Danlos syndrome, n=1, sick-cell disorder, n=1, breast cancer, n=1). While 6 of these deaths has been evaluated as not avoidable, 13 deaths has been considered as possibly (n=12) or certainly (n=1) preventable. The main factor of avoidability was the patient's interaction with the health system (medically non advised pregnancy, lack of adherence to treatment, for example). A pre-pregnancy medical consultation with a specialist should be recommended to all patients with preexisting chronic disease, to allow a complete information about the risks of a pregnancy, treatment adaptation if needed, better adherence and multidisciplinary follow up.

Enhanced modifications of low-density lipoproteins (LDL) by endothelial cells from smokers: a possible mechanism of smoking-related atherosclerosis.

OBJECTIVE: The aim of the study was to investigate LDL modifications by cultured human umbilical vein endothelial cells (HUVEC) from women smokers and non-smokers. METHODS: Modifications of LDL by HUVEC were studied by determining the values of thiobarbituric acid-reactive substances (TBARS) and the percentage of the most electronegative oxidized LDL fraction (fraction C) by using an ion-exchange chromatographic method based on fast protein liquid chromatography (FPLC). We also studied the cellular production of superoxide anion, the effect of various inhibitors and cysteine, and determined total intracellular glutathione content and cell growth. RESULTS: LDL exposed to HUVEC from smokers for 48 h showed significantly greater modifications than LDL exposed to HUVEC from non-smokers, as assessed by TBARS determination (19.4 +/- 1.2, mean +/- s.e.m., n = 20 versus 15.4 +/- 0.7 nmol/mg LDL, n = 19; P < 0.01) and by FPLC (percentage of fraction C: 39 +/- 7, n = 29 versus 14 +/- 3, n = 34; P < 0.001). Moreover, HUVEC from smokers produced significantly more superoxide anion than those from non-smokers (0.46 +/- 0.13 nmol/10(5) cell/min, n = 9 versus 0.22 +/- 0.05, n = 10; P < 0.05). Superoxide production, like cell-induced modification of LDL, was strongly dependent on the presence of cysteine in the medium. Furthermore, HUVEC from smokers had a significantly (P < 0.05) higher total intracellular glutathione content than those from non-smokers (39.9 +/- 3.1 nmol/mg, n = 9 versus 31.8 +/- 2.2, n = 7). Finally, HUVEC from smokers and non-smokers showed similar growth at 48 h. CONCLUSION: HUVEC from smokers converted significantly more LDL into an atherogenic form than HUVEC from non-smokers, a phenomenon that was not due to altered cell growth. HUVEC-mediated LDL modifications were strongly thiol-dependent, as both LDL modifications and superoxide anion production were inhibited in cysteine-free medium. Stimulation of cystine uptake by HUVEC, reflected by the enhanced total glutathione content, could account for the enhanced superoxide anion production. All these observations may be relevant to the pathophysiology of smoking-related cardiovascular disease.

Merging organometallic chemistry with polyoxometalate chemistry

A series of polyoxomolybdate-incorporated organometallic complexes has been obtained by reaction of [MBr(CO)5] or solvated M(CO)3+ ions (M = Mn or Br) with (nBu4N)2[Mo2O7] in methanol, sometimes in the presence of triols of the type RC(CH2OH)3 (R = Me or CH2OH). Their molecular structures are related to those of previously described polyoxoalkoxomolybdates through the formal replacement of fac-MoO2(OR)+ units by topologically equivalent fac-M(CO)3+ units. Representative pairs of structurally related clusters include [Mo2O6(OMe)4-Re(CO)32]2- and [Mo4O10(OMe)6]2-, [Mo2O4MeC(CH2O)32Mn(CO)3]- and [Mo3O6(OMe)MeC(CH2O)32]-, [Mo2O4HOCH2C(CH2O)32Mn(CO)32] and [Mo4O8(OEt)2MeC(CH2O)32], [Mo6O16(OMe)2MeC(CH2O)32-Mn(CO)32]2- and [Mo8O20(OMe)4-MeC(CH2O)32]2-. Although the frameworks of the majority of derivatives are based on tetranuclear units which display the common rhomb-like structure, the alternative cubane-type arrangement is observed in [Mo2O5(OMe)5M(CO)32]-.

Special injuries of the hand.

Unique injuries resulting from high-pressure injection, wringer washers, cornpickers, and snowblowers are presented. Epidemiology, pathophysiology, clinical presentation, and management are reviewed. These injuries commonly require surgical intervention. Prompt recognition and treatment can greatly influence prognosis.

Cervical injury in head trauma.

Criteria for excluding cervical spine injury in patients who have sustained blunt head or neck trauma were prospectively studied at four hospitals in the Chicago area. The authors attempted to define a subset of these adult patients who, based on clinical criteria, could reliably be excluded from cervical spine radiography, thus avoiding unnecessary radiation and saving considerable time and money in their evaluation. Patients fell into four groups: (1) patients who were awake, alert, and had no complaint of neck pain or tenderness on physical examination; (2) patients who were awake, alert, but had complaint of neck pain or tenderness on physical examination laterally over the trapezius muscle only; (3) patients who were awake, alert, but had complaint of central neck pain or tenderness on physical examination over the cervical spine or center of the neck; and (4) patients who were not fully awake or alert, were clinically intoxicated, had other painful or distracting injuries, or had focal neurologic findings. Patients in group 4 had significantly more fractures (21/387) when compared with all other patients (7/478). Patients with central neck pain or tenderness (group 3) had significantly more fractures (7/237) than patients without pain or tenderness or with these findings limited to the trapezius area (0/236). It is clear that patients who have altered mental status, abnormal examination findings, distracting injury, or pain or tenderness over the cervical spine must have cervical spine radiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pathology of gestational trophoblastic tumors]. / Pathologie des tumeurs trophoblastiques gestationnelles.

Gestational trophoblastic tumours result from an abnormal proliferation of different types of trophoblasts. The morphological pattern, together with the immunohistochemical aspect, the cytogenetic data and the clinical profile, helps identify each pathological entity. Hydatiform moles represent malformed placentas caused by genetic aberrations of the villous trophoblast. A complete hydatiform mole displays an hydropic degeneration of all the chorionic villi with a more or less marked proliferation of trophoblasts. A partial hydatiform mole is made up of molar vesicles interspersed with normal chorionic villi. In an invasive hydatiform mole or chorioma destruens, molar vesicles penetrate the myometrium giving rise to a mass distorting the uterine wall. A choriocarcinoma is a malignant proliferation of atypical villous trophoblasts without villi formation. Necrosis, haemorrhage, vascular invasion and distant metastases strongly compromise its outcome. A trophoblastic implantation site tumor, clearly less frequent, results from a proliferation of extravillous trophoblasts, particular for their secretion of human placental lactogen hormone (hPL). This tumour, exceptionally malignant, should be differentiated from the exaggerated placental site and its variants. Except for the placental site trophoblastic tumour, and whatever the outcome (benign or malignant), all gestational trophoblastic tumours secrete the beta-subunit of the chorionic gonadotropic hormone (beta-hCG) more or less abundantly. The serum or urinary level of this unit is proportional to the tumour volume and represents a fundamental basis for the follow-up of these tumours. Multidisciplinary care of high-risk cases allows us to cure the disease, and helps the patient recover her reproductive uterine function.

[Towards another diagnostic approach of peripheral pulmonary masses. Ultrasound-guided puncture]. / Vers une autre approche du diagnostic des masses pulmonaires périphériques. La ponction échoguidée.

In a series of 50 patients with lung lesions touching the thoracic wall, percutaneous ultrasonically guided needle aspiration yielded a pathological diagnosis in 44 cases (sensitivity: 88%). The histological diagnosis of malignant lesion could be confirmed in 41 of these 44 patients. In this group of patients with neoplasia the diagnosis obtained by extemporaneous cytology was compared with that obtained by lung biopsy: the diagnostic sensitivity of cytology proved to be higher than that of biopsy (86.36% and 65.90% respectively). Using the two methods concomitantly increased sensitivity up to 93.18%. A pathological diagnosis could be obtained in 3 out of the 6 patients in this series who had benign lesions.

[Future of coelioscopy tappings of ovarien cysts (author's transl)]. / Quel est l'avenir des ponctions per-coelioscopiques des kystes ovariens?

In a study of 136 tapping of ovarien cysts carried out in the surgical departement of Broca Hospital from 1968 to 1971, the authors point out the diagnostic interest of such a practice, which is harmeless if the contra-indications are respected and often easily carried out (tapping needle by Mintz). The macroscopic and cytological aspect of the liquid tapped enable one to make a precise diagnostic in almost all cases and to lead the therapy in the proper direction.

[Transabdominal amnio-infusion facilitates external version maneuver after initial failure. Six successful attempts]. / L'amnio-infusion transabdominale facilite la version par manoeuvre externe après échec préalable de celle-ci. A propos de 6 réussites.

External version was successful after initial failure in 6 cases after transabdominal amnio-infusion. Filling the uterine cavity by amnio-infusion with 700 to 900 ml saline solution at 37 degrees C facilitated cephalic presentation in these 6 cases. In each case, a prior version attempt had been unsuccessful. Amnio-infusion was performed under continuous sonographic monitoring before a second attempt the next day. The clinical situation was different in the 6 cases which all terminated by normal cephalic delivery. Two patients were first parity, another has a single uterine scar, 3 had a normal pelvis (Magnin > 23), one a narrow pelvis (Magnin = 22.7) and 2 had a pelvis considered pathological (Magnin < 22). The main goal of this preliminary study was to evaluate the feasibility and safety of this new indication for transabdominal amnio-infusion. This new indication should be evaluated by several clinical trials, but it would new appear reasonable to propose transabdominal amnio-infusion in patients with a pathological pelvis and/or a single cicatricial uterus.