Contribution of blood detection of insulin-like growth factor binding protein-1 for the diagnosis of amniotic-fluid embolism: a retrospective multicentre cohort study.

OBJECTIVE: To assess the contribution of maternal blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism in clinical daily practice. DESIGN: A retrospective multicentre cohort study. SETTING: Three tertiary care obstetric units in France. SAMPLE: Data of 86 women for whom amniotic-fluid embolism had been suspected and maternal serum detection of IGFBP-1 had been performed between 2011 and 2019 were analysed. METHODS: The criteria defined by the United Kingdom Obstetric Surveillance System (UKOSS) were used for the retrospective diagnosis of amniotic-fluid embolism. The more structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation (SMFM) was also used as secondary endpoint. MAIN OUTCOME MEASURES: Agreements between biological and clinical assessments were tested. The performance of blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism according to the UKOSS criteria, and to the SMFM definition, was also assessed. RESULTS: There was only slight agreement between clinical and laboratory diagnosis of amniotic-fluid embolism (Cohen's Kappa coefficient: 0.04). Blood detection of IGFBP-1 had a sensitivity of 16%, a specificity of 88%, a positive and a negative likelihood ratio of 1.3 and 0.95, respectively, and a positive and a negative predictive value of 58 and 50%, respectively, for the diagnosis of amniotic-fluid embolism based on the UKOSS criteria. The use of the more structured SMFM definition of amniotic-fluid embolism did not substantially change the results. CONCLUSION: These results question the usefulness of blood detection of IGFBP-1 for the early diagnosis of amniotic-fluid embolism in daily clinical practice. TWEETABLE ABSTRACT: This retrospective multicentre study questions the contribution of IGFBP-1 detection for the diagnosis of AFE.

Behavior of Antimicrobial Peptide K4 in a Marine Environment.

K4 is a de novo peptide with antibacterial activity on human pathogens. It has a short sequence (14 amino acids), with a cationic N-terminal moiety and an amphipathic ɑ-helix structure. The present paper demonstrates its activity on Vibrio bacteria in a marine environment. It was found non-toxic on marine organisms including Artemia salina, Dicentrarchus labrax, and Magallana gigas at different developmental stages, but influenced the growth of unicellular organisms like microalgae, depending on the algal strain and on K4 concentration. Furthermore, an original approach coupling liquid chromatography (RP-HPLC) and mass spectrometry (MS/MS) allowed us to monitor the degradation time course of the peptide for the first time in conditions close to a hatchery environment, i.e., in the presence of oyster spat. We detected truncated forms over time, and the full K4 was gradually no longer found in these filter-feeder oysters. Finally, using an automated optical density meter, we monitored the growth of several aquatic bacteria identified as pathogenic on animals. K4 had a bactericidal effect on Aeromonas salmonicida and Vibrio splendidus LGP32 at concentrations below 45 µg mL-1. Our results show that K4 could be an environment-friendly alternative to antibiotics, non-toxic to several marine organisms. The use of K4 would be particularly useful to decrease the bacterial load associated with food intake in the early developmental stages of marine animals reared in hatcheries.

[Acyclovir-resistant perineal HSV infection revealing chronic lymphoid leukaemia]. / Herpès chronique périnéal résistant à l'aciclovir révélateur d'une leucémie lymphoïde chronique.

BACKGROUND: Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia. PATIENTS AND METHODS: An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later. DISCUSSION: The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia. CONCLUSION: Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered.

Wound closure with Karydakis flap is decreasing the perioperative costs after pilonidal sinus excision as compared to lay-open approach.

PURPOSE: To assess the impact of a simple flap closing procedure by Karydakis flap (KF) after pilonidal sinus excision on the costs and healing time as compared to routine lay-open technique. METHOD: Out of 44 consecutive patients operated on for pilonidal excision (November 2013-March 2015), 17 had a Karydakis flap and 27 a lay-open procedure. For each patient, the length of stay, the operating time (OT), the time needed for complete healing and postoperative care resources were recorded. The global costs included OT, nursing care quantity, and modalities until complete scar healing. RESULTS: One reoperation in the lay-open group was necessary during the follow-up (8±5months). No recurrence occurred. Postoperative morbidity was similar in both groups. Results showed that KF global cost was inferior as compared to lay-open technique (941±178€ vs. 1601±399€; P=0.0001), KF healed faster (32±17 vs. 59±22days; P=0.0001), whereas OT was longer in KF group (16±7 vs. 25±4min; P=0.001). CONCLUSION: KF allows a faster healing time and a 41% lower cost than lay-open technique. Preferential use of KF rather than lay-open procedure could allow a significant health cost saving.

Pan-genome multilocus sequence typing and outbreak-specific reference-based single nucleotide polymorphism analysis to resolve two concurrent Staphylococcus aureus outbreaks in neonatal services.

We used a two-step whole genome sequencing analysis for resolving two concurrent outbreaks in two neonatal services in Belgium, caused by exfoliative toxin A-encoding-gene-positive (eta+) methicillin-susceptible Staphylococcus aureus with an otherwise sporadic spa-type t209 (ST-109). Outbreak A involved 19 neonates and one healthcare worker in a Brussels hospital from May 2011 to October 2013. After a first episode interrupted by decolonization procedures applied over 7 months, the outbreak resumed concomitantly with the onset of outbreak B in a hospital in Asse, comprising 11 neonates and one healthcare worker from mid-2012 to January 2013. Pan-genome multilocus sequence typing, defined on the basis of 42 core and accessory reference genomes, and single-nucleotide polymorphisms mapped on an outbreak-specific de novo assembly were used to compare 28 available outbreak isolates and 19 eta+/spa-type t209 isolates identified by routine or nationwide surveillance. Pan-genome multilocus sequence typing showed that the outbreaks were caused by independent clones not closely related to any of the surveillance isolates. Isolates from only ten cases with overlapping stays in outbreak A, including four pairs of twins, showed no or only a single nucleotide polymorphism variation, indicating limited sequential transmission. Detection of larger genomic variation, even from the start of the outbreak, pointed to sporadic seeding from a pre-existing exogenous source, which persisted throughout the whole course of outbreak A. Whole genome sequencing analysis can provide unique fine-tuned insights into transmission pathways of complex outbreaks even at their inception, which, with timely use, could valuably guide efforts for early source identification.

[Intra-uterine growth restriction impact on maternal serum concentration of PlGF (placental growth factor): A case control study]. / Impact du retard de croissance intra-utérin sur la concentration sérique maternelle du PlGF (Placental Growth Factor) : une étude cas-témoin.

OBJECTIVES: Placental growth factor (PlGF) is a pro-angiogenic factor mainly assessed in preeclampsia in which its blood concentration is decreased. The aim of this study was to dose the blood concentration of PlGF in women with fetal intra-uterine growth restriction (IUGR) without associated preeclampsia at the time of diagnosis. METHODS: Case/control study: IUGR was defined by a fetal biometry with abnormal uterine and/or umbilical doppler (n=23). This group was compared to a control group of fetuses (n=25) matched for gestational age at blood sampling for the dosage of maternal seric PlGF. Women with preeclampsia were not included. RESULTS: The plasma PlGF concentration was 11pg/mL (IQR [11-42,8]) in the IUGR group vs 287pg/mL [135-439] in the control group (P<0.001) and this difference was available after adjustment for gestational age at the time of blood sampling (P<0.001). PlGF sensitivity and specificity for discrimination were respectively 87% (CI 95% [66-97]) and 88% (CI 95% [69-97]). CONCLUSION: Maternal serum PlGF concentrations were very low in IUGR group compared with those of the control group.

[Reynolds syndrome revealing a malignant thymoma]. / Un syndrome de Reynolds révélant un thymome malin.

INTRODUCTION: Thymomas, benign or malignant, may be associated with autoimmune diseases. They are classically associated with myasthenia gravis, neuromyotonia, or pure red cell aplasia. CASE REPORT: We here report, to the best of our knowledge, the first description of an association between thymoma and Reynolds syndrome (systemic sclerosis associated with primary biliary cirrhosis) in an 80-year-old woman. CONCLUSION: The suspected pathogenesis of this association could be a thymus escape of auto-reactive T lymphocytes and the consecutive development of an auto-immune disorder.

Rationalization of the entrapping of bioactive molecules into a series of functionalized porous zirconium terephthalate MOFs.

The encapsulation of two different bioactive molecules, the cosmetic caffeine and the analgesic and anti-inflammatory ibuprofen, has been evaluated by combining impregnation and advanced characterization experimental tools in a series of microporous rigid zirconium(iv) terephthalates UiO-66 bearing different polar or apolar functional groups (-H, -Br, -NH2, -2OH, -NO2, -Cl, -2CF3, -CH3, -2CH3). It has been first evidenced that these hybrid solids exhibit drug payloads that significantly outperform those obtained using current drug formulations or other conventional porous solids. A quantitative structure-activity relationship strategy has been further conducted with the aim of rationalizing the experimental drug uptakes and further emphasizing the most relevant chemical and structural features that significantly impact their encapsulation performances. Indeed, it appears that the caffeine loading is optimized when the functionalized organic linker both shows a large octanol-water partition coefficient and contains grafted functions with low hydrogen bond acceptor abilities, whereas the ibuprofen entrapping is enhanced when the organic linker contains functional groups with a large solvent surface area and free volume, and to a lesser extent low hydrogen bond acceptor abilities. Moreover, it has been shown that the solvent used as media for the biomolecule impregnation plays a crucial role in the encapsulation performance due to the formation of a competitive adsorption process between the solvent and the active molecule.

[Completeness and quality of multidisciplinary team meetings: the example of prostate cancer in the Mid-Pyrenees region]. / Exhaustivité et qualité des réunions de concertation pluridisciplinaire: l'exemple des cancers prostatiques en Midi-Pyrénées.

OBJECTIVES: To determine the completeness of the examination of cancer patient cases in a multidisciplinary team meeting (MDTM), to study the factors that can affect this examination and to assess the quality of the MDTM concerning prostate cancer in Tarn. METHODS: Completeness was estimated by comparing the database of the Tarn cancer registry containing all the inhabitants of this department for whom prostate cancer was diagnosed in 2007 with the list of patients living in Tarn whose cases were discussed during a Midi-Pyrénées MDTM. Determinants of the case discussion in MDTM were studied from data collected in medical records (age, stage at diagnosis, PSA level, Gleason score, treatment). The MDTM quality study (delay in management, whether the case was seen before or after treatment, required elements for MDTM, clinical data, conformity between suggested treatment and guidelines, adequacy between suggested and performed treatments) was based on the MDTM forms retrieved from the DCO and from medical records. RESULTS: Four hundred and fifty-nine patients were re-examined. The pretherapeutic passage rate within three months after diagnosis was 56.2%. The probability of a discussion in MDTM decreased for people over 85 years of age (OR=0.10) compared with the 70-74 year-old people and it increased for the N+M+ (OR=4.23) compared with the T1-T2. Patients for whom radiotherapy was considered were presented more frequently than the others. The MDTM quality was studied based on 220 DCO forms. The patient's physician attended the MDTM in 65% of the cases, 97% of the suggested treatments were consistent with the guidelines and 90% of the performed treatments complied with the suggested treatment. CONCLUSION: The discussion rate in MDTM has not reached the 100% planned by the first "plan cancer" yet, but when a MDTM was carried out, its compliance and adequacy were high. While seniors' cases require interdisciplinarity because of a complicated management, they were less discussed in MDTM.

Efficacy of oxyclozanide against the rumen fluke Calicophoron daubneyi in experimentally infected goats.

Paramphistome infections are very common in ruminants and may induce clinical signs, but little is known about effective treatments. In this study, the efficacy of oxyclozanide against Calicophoron daubneyi was studied in goats and its activity tested against immature stages (10 days post-infection) at a dose of 22.5mg/kg bodyweight (BW) and against adult stages using two doses (15 and 22.5mg/kg BW). There was a reduction (82%) in the number of immature worms (compared to controls) but the result was not statistically significant. When tested against adult stages, however, oxyclozanide reduced the worm burdens by 95.6% and 95.9% at doses of 15 and 22.5mg/kg BW, respectively, with no significant difference between the two doses. The experiment demonstrated that oxyclozanide is highly effective in reducing the number of adult paramphistomes in goats.

Perineal pain and inferior cluneal nerves: anatomy and surgery.

Neuropathic perineal pains are generally linked to suffering of the pudendal nerve. But some patients present pains described as a type of burning sensation located more laterally on the anal margin and on areas including the scrotum or the labiae majorae, the caudal and medial parts of the buttock and the upper part of the thigh. These pains extend beyond the territory of the pudendal nerve. It is interesting to note that the inferior cluneal nerves are responsible for the cutaneous sensitivity in the inferior part of the buttock. We wanted to check if these nerves, or some of their branches, could be responsible for such pains. An anatomic study, containing six dissections on corpse, has been conducted. The inferior cluneal nerves, emerging from the posterior femoral cutaneous nerve have some branches joining the perineum, especially by a perineal ramus. However, two conflict areas have been identified on the path of these nerves and on the perineal ramus: one at the level of the sacrotuberal ligament, and the other being the passage under the ischium. Two surgical approaches have been established from these observations with the aim of suppressing the conflicts.

p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.

Human telomerase is regulated by erythropoietin and transforming growth factor-beta in human erythroid progenitor cells.

Telomerase catalytic subunit (hTERT) exerts important cellular functions including telomere homeostasis, genetic stability, cell survival and perhaps differentiation. However, the nature of external or internal signals, which regulate hTERT expression in tissues, remains poorly understood. Thus, whereas it has been described that hTERT gene is regulated along the differentiation of primitive myeloid progenitors, the effect of specific cytokines on telomerase expression in each myeloid lineage is currently unknown. Based on these considerations, we have investigated hTERT expression in erythroid cells treated with erythropoietin (EPO) and transforming growth factor beta (TGFbeta), as putative positive and negative regulators, respectively. We describe here that EPO activates hTERT gene transcription in in vitro-expanded primary erythroid precursors as well as in UT7 erythroleukemia cells. In UT7 cells, this study shows also that EPO acts through a JAK2/STAT5/c-myc axis. In contrast, TGFbeta blocks EPO signaling downstream of c-myc induction through a Smad3-dependent mechanism. Finally, hTERT appears to be efficiently regulated by EPO and TGFbeta in an opposite way in erythropoietic cells, arguing for a role of telomerase in red blood cell production.

[Anti PM-Scl antibodies. Study of prevalence and of meaning]. / Autoanticorps anti-PM-Scl. Etude de prévalence et de signification.

OBJECTIVE: The purpose of our study is to appreciate the prevalence of antibodies anti PM-Scl within the framework of antinuclear antibodies detection and to clarify clinical biological and evolutive features associated to these antibodies. METHODS: 9,747 consecutive antinuclear testing datas allowed us to evaluate anti PM-Scl antibodies frequency. A retrospective analysis of patients characteristics was performed to identify clinical, biological and evolutive signs associated with this antibody over a five years follow up period. RESULTS: Over the 9,747 samples tested for antinuclear antibodies detection, 3,493 (35.8%) are positive. An anti ENA activity is observed in 727 (7.5%) cases and anti PM-Scl in 6 (0.06%). These antibodies are described in systemic sclerosis, myositis or overlap syndromes. All theses diseases showed a low evolutivity over the five years of follow up. CONCLUSIONS: Low prevalence and possible association with an overlap autoimmune syndrome of quite good prognosis are reported with anti PM-Scl antibodies.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Structure and magnetism of [M3](6/7+) metal chain complexes from density functional theory: analysis for copper and predictions for silver.

The ground-state electronic structure of the trinuclear complex Cu3(dpa)4Cl2 (1), where dpa is the anion of di(2-pyridyl)amine, has been investigated within the framework of density functional theory (DFT) and compared with that obtained for other known M3(dpa)4Cl2 complexes (M = Cr, Co, Ni) and for the still hypothetical Ag3(dpa)4Cl2 compound. Both coinage metal compounds display three singly occupied x2-y2-like (delta) orbitals oriented toward the nitrogen environment of each metal atom, generating antibonding M-(N4) interactions. All other metal orbital combinations are doubly occupied, resulting in no delocalized metal-metal bonding. This is at variance with the other known symmetric M3(dpa)4Cl2 complexes of the first transition series, which all display some delocalized bonding through the metal backbone, with formal bond multiplicity decreasing in the order Cr > Co > Ni. An antiferromagnetic coupling develops between the singly occupied MOs via a superexchange mechanism involving the bridging dpa ligands. This magnetic interaction can be considered as an extension to the three aligned Cu(II) atoms of the well-documented exchange coupling observed in carboxylato-bridged dinuclear copper compounds. Broken-symmetry calculations with approximate spin projection adequately reproduce the coupling constant observed for 1. Oxidation of 1 removes an electron from the magnetic orbital located on the central Cu atom and its ligand environment; 1+ displays a much weaker antiferromagnetic interaction coupling the terminal Cu-N4 moieties via four ligand pathways converging through the x2-y2 orbital of the central metal. The silver homologues of 1 and 1+ display similar electronic ground states, but the calculated magnetic couplings are stronger by factors of about 3 and 4, respectively, resulting from a better overlap between the metal centers and their equatorial ligand environment within the magnetic orbitals.