WO2004086043A1 - Prediction et detection d'une infection de plaie - Google Patents

Prediction et detection d'une infection de plaie Download PDF

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Publication number
WO2004086043A1
WO2004086043A1 PCT/GB2004/001294 GB2004001294W WO2004086043A1 WO 2004086043 A1 WO2004086043 A1 WO 2004086043A1 GB 2004001294 W GB2004001294 W GB 2004001294W WO 2004086043 A1 WO2004086043 A1 WO 2004086043A1
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WO
WIPO (PCT)
Prior art keywords
wound
marker
concentration
infection
tnf
Prior art date
Application number
PCT/GB2004/001294
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English (en)
Inventor
Breda Mary Cullen
Original Assignee
Johnson & Johnson Medical Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0306979A external-priority patent/GB2399881B/en
Application filed by Johnson & Johnson Medical Limited filed Critical Johnson & Johnson Medical Limited
Publication of WO2004086043A1 publication Critical patent/WO2004086043A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869—Interleukin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere

Definitions

  • the present invention relates to a method of predicting or diagnosing clinical infection of a wound comprising measuring the concentration of a marker associated with an inflammatory response in wound fluid, in particular the concentration of a proinflammatory cytokine.
  • the present invention also relates to devices and kits for use in such methods.
  • Wound healing is a complex dynamic process that results in the restoration of anatomic continuity and function; an ideally healed wound is one that has returned to normal anatomic structure, function and appearance.
  • Chronically contaminated wounds all contain a tissue bacterial flora. These bacteria may be indigenous to the patient or might be exogenous to the wound. Closure, or eventual healing of the wound is often based on a physician's ability to control the level of this bacterial flora.
  • a prognostic aid that would assist in predicting clinical infection of a wound prior to obvious clinical symptoms of infection.
  • Such a prognostic aid would allow early intervention with suitable treatment (e.g. a topical antimicrobial treatment) before wound chronicity sets in.
  • suitable treatment e.g. a topical antimicrobial treatment
  • diagnostic aid that would assist in the early diagnosis of clinical infection, preferably allowing diagnosis prior to obvious clinical symptoms of infection.
  • Tumor Necrosis Factor Alpha is a proinflammatory cytokine that is released by activated macrophages and lymphocytes.
  • Mature human TNF- ⁇ is peptide of 157 amino acid residues. It binds to receptors present on the surface of most cells to produce a wide range of effects, due to its ability to activate multiple signal transduction pathways, and to its ability to induce or suppress the expression of a vast number of genes, including those for growth factors and cytokines.
  • TNF- ⁇ has been implicated in a range of disorders, including cachexia (progressive wasting), septic shock, autoimmune disorders, bacterial toxic shock, graft versus host disease, HIV infection and AIDS.
  • a method of predicting or diagnosing clmical infection of a wound comprising measuring the concentration of a marker associated with an inflammatory response in wound fluid, wherein the marker is a proinflammatory cytokine.
  • a wound dressing or biosensor comprising components of an assay system for measuring the concentration of a marker associated with an inflammatory response, wherein the marker is a proinflammatory cytokine, for use in the manufacture of a medicament for predicting the likelihood of clinical infection of the wound or for diagnosing clinical infection of a wound.
  • the preferred proinflammatory cytokine is TNF- ⁇ .
  • Further examples include: Interleukins such as IL-lbeta, IL-4, IL-6, IL-8, IL-10, IL-18, MCP-1, MCP-2, MCP-3 Monocyte chemoattractant proteins, MIP-1 alpha, MlP-lbeta, MIP-2 Macrophage inflammatory proteins, Interferons IFN-alpha, IFN-beta, and IFN-gamma, GM-CSF Granulocyte/macrophage colony stimulating factor, PF-4 Platelet factor 4, RANTES a member of the chemokine family.
  • Interleukins such as IL-lbeta, IL-4, IL-6, IL-8, IL-10, IL-18, MCP-1, MCP-2, MCP-3 Monocyte chemoattractant proteins, MIP-1 alpha, MlP-lbeta, MIP-2 Macrophage inflammatory proteins, Interferons I
  • wound fluid refers to any wound exudate or other fluid (preferably substantially not including blood) that is present at the surface of the wound, or that is removed from the wound surface by aspiration, absorption or washing.
  • wound fluid does not refer to blood or tissue plasma remote from the wound site.
  • concentration of more than one marker may be measured. In certain embodiments, the concentrations of at least two, three or four markers are monitored.
  • Measuring the concentration of a marker associated with an inflammatory response in wound fluid allows the likelihood of (or the presence of) clinical infection to be assessed.
  • the step of measuring is preferably carried out on wound fluid that has been removed from the body of the patient, but can also be performed on wound fluid in situ.
  • the wound may be an acute wound such as an acute traumatic laceration, perhaps resulting from an intentional operative incision, or the wound may be a chronic wound.
  • the method / use of the invention is envisaged as being most useful in predicting or diagnosing clinical infection of a chronic wound.
  • the chronic wound is selected from the group consisting of venous ulcers, pressure sores, decubitis ulcers, diabetic ulcers and chronic ulcers of unknown aetiology.
  • Chronic wound fluids inherently have levels of markers such as neutrophil elastase that are many times the level found in normal, acute wound fluids. Nevertheless, it has now been found that the levels of such markers are further elevated by a substantial amount when the chronic wound will become infected.
  • the prognostic / diagnostic assay is designed so as to provide a correlation between a given concentration of a marker of an inflammatory response and the likelihood of (or presence of) clinical infection.
  • concentration levels of markers of the inflammatory response which are indicative of subsequent progression to clinical infection and/or of the presence of clinical infection.
  • a concentration at least 1.5-, 2-, 2.5-, 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 5.5-, 6.0-, 7.0-, 8.0- or 9.0-fold the basal level of the marker is considered as begin indicative of subsequent progression to clinical infection.
  • measuring the concentration of a marker associated with an inflammatory response we also include techniques that produce a positive or negative signal if the marker is present at one or more of these concentrations.
  • a concentration at least 1.5-, 2-, 2.5-, 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 5.5-, 6.0-, 7.0-, 8.0-, 9.0-, 10.0-, 11.0-, 12.0- 14.0-, 16.0-fold the basal level of the marker is considered as begin indicative of the presence of clinical infection.
  • concentration of a marker associated with an inflammatory response we also include techniques that produce a positive or negative signal if the marker is present at one or more of these concentrations.
  • the basal level of the marker we include the level of the marker normally associated with a wound which is not clinically infected and which does not subsequently become clinically infected. It will be appreciated that the basal level of the marker may be much higher for a chronic wound than for a normal, acute wound.
  • wound fluid is meant to refer to the exudate that is secreted or discharged by cells in the environment of the wound. This fluid contains cells, both living and dead, and a variety of inflammatory cytokines.
  • concentration of a marker of an inflammatory response is meant the free concentration of the marker in the wound fluid.
  • concentration of the marker may be assessed in situ, or alternatively a sample of wound fluid may be taken as a clinical swab or as a fluid sample.
  • the concentration of the marker of the inflammatory response may be measured by any method known to those of skill in the art. Suitable methods include those utilising chemical or enzyme-linked reactions, or immunological (e.g. ELISA, western blots), spectrophotometric, colorimetric, fluorimetric, or radioactive detection based techniques. In one embodiment the concentration of the marker is measured by a dip-stick type test. Such a test could be used in the community and by the patient allowing easier and earlier diagnosis.
  • a sample of wound fluid must be added to the assay system. Measurement may either be made in situ, or fluid may be removed from the wound for subsequent analysis. The decision as to which method is used will depend upon the type of wound in question. For example, in the case of surface-exposed wounds, a clinical swab, dressing, "dipstick” or other biosensor device may be applied directly to the surface of the wound. The device should contain the components of the assay system for measuring the concentration of the marker so that the assay reaction may itself proceed in situ.
  • the device can then be removed from the wound and the signal measured by the appropriate means.
  • a physician may not actually require an accurate assessment of the precise concentration of the marker, but may just wish to know whether there is a sufficient concentration of the marker to warrant prophylactic or curative action as necessary. In these cases, visible assessment of the dressing may be sufficient to allow identification of the specific areas of infection. Unnecessary treatment of healthy granulating tissue can then be avoided.
  • a dressing that allows mapping of the infected areas of a wound will be preferable in certain instances.
  • Diagnostic wound mapping sheets that could be adapted to the methods of the present invention are described in GB2323166 (application no. GB 9705081.9), filed on 12th March 1997, the entire content of which is hereby incorporated by reference.
  • Immobilisation of reaction components onto a dipstick, wound mapping sheet or other solid or gel substrate offers the opportunity of perforrning a more quantitative measurement.
  • the device may be transferred to a spectrometer. Suitable methods of analysis will be apparent to those of skill in the art.
  • Immobilisation of the reaction components to a small biosensor device will also have the advantage that less of the components (such as enzyme and substrate) are needed.
  • the device will thus be less expensive to manufacture than a dressing that needs to have a large surface area in order to allow the mapping of a large wound area.
  • the concentration of the marker may alternatively be measured in an aqueous assay system.
  • Wound fluid may be extracted directly from the environment of the wound or can be washed off the wound using a saline buffer. The resulting solution can then be assayed for the concentration of the marker in, for example, a test tube or in a microassay plate.
  • Such a method will be preferable for use in cases in which the wound is too small or too inaccessible to allow access of a diagnostic device such as a dipstick.
  • This method has the additional advantage that the wound exudate sample may be diluted.
  • an aqueous assay system is more applicable to use in a laboratory environment, whereas a wound dressing containing the necessary reaction components will be more suitable for use in a hospital or domestic environment.
  • Figure 1 shows the amounts of TNF- ⁇ detected in cell culture supernatants over time for THP-1 monocyte/macrophage cells stimulated by the presence of various concentrations of bacterial lipopolysaccharide, at 2xl0 6 cells/ml for 1,4,24 and 48 hours incubated at 37°C
  • Wound fluid was collected from two patients having diabetic foot ulcers of at least 30 days duration and a surface area of at least 1cm 2 .
  • the first patient did not exhibit any clinical signs of infection at the time of taking of the wound fluid sample, or within 14 days thereafter.
  • the second patient showed clinical signs of wound infection at the time that the sample was taken.
  • the protein binding solution comprises 1 ml Coomassie Brillant Blue stock solution 200mg-Coomassie Brillant Blue G250, Sigma Chemical Co., dissolved in 50 ml ethanol-90%); 2ml orthophosphoric acid (85% w/v); in a final volume of 20 ml with distilled water. This solution was filtered (Whatman #1 filter paper) and used immediately.
  • the protein level in a sample wound fluid was measured by mixing 10- ⁇ l sample or standard with 190- ⁇ l of the protein binding solution in a microtitre well and incubating for 30mins at ambient temperature prior to reading absorbance at 595nm.
  • the concentration of protein was estimated from a standard calibration of BSA (bovine serum albumin prepared in distilled water; Sigma Chemical Co.) ranging from 1.0 to 001 mg/ml.
  • the levels of TNF- ⁇ present in the samples were measured by an ELISA method using a
  • the assay employs the quantitative sandwich enzyme immunoassay technique.
  • a monoclonal antibody specific for TNF- ⁇ is pre-coated onto a microplate.
  • Standards and samples are pipetted into the wells of the microplate, and any TNF- ⁇ is bound by the immobilised antibody.
  • an ezyme-linked polyclonal antibody specific for TNF- ⁇ is added to the wells.
  • a substrate solution is added to the wells and colour develops in proportion to the amount of TNF- ⁇ bound in the initial step.
  • the colour development is stopped and the intensity of the colour is measured.
  • the enzyme used is horse radish peroxidase
  • the colour reagents are stabilised hydrogen peroxide and stabilised tetramethyl benzidene chromogen,. and the stop solution is 2M sulphuric acid.
  • the non-infected wound fluid contained 22.2 pg/ml, and when adjusted for total protein 6.36 pg/ml/mg of TNF- ⁇ .
  • the infected wound fluid contained 135.6 pg/ml, and when adjusted for protein 64.2 pg/ml/mg of TNF- ⁇ . It can thus be seen that a very considerable increase of the TNF- ⁇ levels is seen upon infection of a chronic wounds.
  • Neutrophils were isolated from whole blood by Ficoll-Hypaque density gradient centrifugation, according to the method of Moseley et al (1997). Briefly, whole blood (40ml) was removed from healthy, human volunteers (age range 20-30 years) into vacutainers containing EDTA (Becton Dickinson, Meylan Cedex, France) as an anticoagulant.
  • EDTA Becton Dickinson, Meylan Cedex, France
  • Ficoll-Hypaque density gradient consisting of a dense Ficoll-Hypaque layer (10ml), comprised of 9.5% Ficoll 400 (Amersham Pharmacia Biotech, Buckinghamshire, U.K.) and 17% Hypaque solution (sodium diatrizoate, Intrapharm Laboratories, Gwent, U.K.) and a light Ficoll-Hypaque layer (10ml), consisting of comprised of 8.17% Ficoll 400 and 10% Hypaque solution. Tubes were centrifuged at 2500rpm/45min at room temperature, resulting in the formation of four definite layers.
  • the two upper layers consisting of plasma and lymphocytes/monocytes respectively, were removed and discarded.
  • Each third layer containing the neutrophils, was removed and pooled into a separate tube, with each remaining erythrocyte layer, also being discarded.
  • Equal volumes of PBS were added to the pooled neutrophil layers and centrifuged at 2000 m/5min at room temperature.
  • the supernatant layer removed and pellet resuspended in PBS and centrifuged at 2000 ⁇ m/5mins at room temperature. Any erythrocyte contamination of the PMN pellet was removed by adding cold 0.2% sodium chloride (5ml) and the tube agitated for lmin.
  • the osmolarity within the tube was corrected by the addition of 1.6% sodium chloride, followed by gentle agitation.
  • An equal volume of PBS (10ml) was added and the tube centrifuged at 2000rpm/5min at room temperature. Once erythrocyte contamination had been removed, the PMN pellet was washed once in PBS (5ml), centrifuged at 2000rpm/5min, as above, and resuspended in RPMI-1640 medium (Gibco BRL, Paisley, U.K.), supplemented with L-glutamine (2mM) (Gibco BRL), prior to assessment for amount of contamination by other cell types (visual assessment), cell viability determination and cell counting.
  • Neutrophils were seeded in the appropriate culture media into 24-well tissue culture plates at a cell density of 2 x 10 6 cells/0.5ml and/or 5 x 10 5 cells/0.5ml. Cells were then stimulated with equal volumes of LPS E.coli 055 :B5 was added at a final concentration of 100, 10, 1, 0.1 ng/ml for lh, 4h, 24h, and 48 h at 37°C in 5% C0 2 . Media alone and cells incubated with media only served as the negative control. Culture media was removed, aliquoted and immediately frozen at -70°C.
  • the amount of TNF- ⁇ detected in the cell culture supernatant at 4 hours had increased to 50pg/ml and at 24 hours had increased to 220pg/ml. This illustrates the prompt response of TNF- ⁇ level to bacterial contamination.
  • TNF- ⁇ The production of TNF- ⁇ from a monocyte/macrophage cell line cultured in vitro was studied as follows, in order to determine the effect of bacterial lipopolysaccharide on TNF production.
  • THP-1 cells monocyte/macrophage cell line were maintained in culture in RPMI-1640 medium containing 2mM L-glutamine (Gibco BRL, Paisley, UK) supplemented with 10% foetal calf syndrome. The cells were then stimulated with different concentrations of bacterial LPS, and measurements taken as described for Example 2.

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Abstract

L'invention concerne une méthode de prédiction ou de diagnostic d'une infection clinique d'une plaie. Cette méthode consiste à mesurer la concentration d'un marqueur associé à une réponse inflammatoire dans un fluide de plaie. Le marqueur est une cytokine pro-inflammatoire, notamment TNF-α. L'invention concerne également une utilisation d'un pansement de plaie ou d'un biocapteur comprenant des constituants d'un système d'essai pour mesurer la concentration d'un marqueur associé à une réponse inflammatoire. Le marqueur de l'invention est une cytokine pro-inflammatoire, notamment TNF-α, destinée à la fabrication d'un médicament permettant de prédire la probabilité d'une infection clinique d'une plaie ou destinée à diagnostiquer une infection clinique d'une plaie.
PCT/GB2004/001294 2003-03-26 2004-03-25 Prediction et detection d'une infection de plaie WO2004086043A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0306979.6 2003-03-26
GB0306979A GB2399881B (en) 2003-03-26 2003-03-26 Prediction and detection of wound infection
US49275003P 2003-08-06 2003-08-06
US60/492,750 2003-08-06

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WO2004086043A1 true WO2004086043A1 (fr) 2004-10-07

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2430030A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2430029A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2430031A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2447865A (en) * 2007-03-30 2008-10-01 Ethicon Inc Diagnostic markers of wound infection
WO2009066075A2 (fr) * 2007-11-20 2009-05-28 Convatec Technologies Inc Marqueurs de diagnostic d'une infection de lésion
WO2009122188A2 (fr) * 2008-04-04 2009-10-08 Axis-Shield Diagnostics Ltd Procédé de contrôle d'infection de plaie
WO2013026999A1 (fr) 2011-08-19 2013-02-28 Pulse Innovate Ltd Système de gestion de plaies
US9708661B2 (en) 2008-04-03 2017-07-18 Becton, Dickinson And Company Advanced detection of sepsis
US10443099B2 (en) 2005-04-15 2019-10-15 Becton, Dickinson And Company Diagnosis of sepsis
EP3901277A1 (fr) 2020-04-24 2021-10-27 Paul Hartmann AG Procédé et dispositif pour évaluer l'état d'une plaie d'un patient
EP3901276A1 (fr) 2020-04-24 2021-10-27 Paul Hartmann AG Procédé et dispositif pour évaluer l'état d'une plaie d'un patient

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WO2000008203A1 (fr) * 1998-08-05 2000-02-17 Johnson & Johnson Medical Limited Procede de controle de la contamination bacterienne d'une plaie
WO2000065083A2 (fr) * 1999-04-26 2000-11-02 The Procter & Gamble Company Protections periodiques feminines jetables pourvues d'un moyen de detection du sang, en tant que capteur
US6426227B1 (en) * 1999-08-31 2002-07-30 Common Sense Ltd. Method for analyzing secreted bodily fluids
US6478938B1 (en) * 2000-05-24 2002-11-12 Bio Digit Laboratories Corporation Electrochemical membrane strip biosensor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000008203A1 (fr) * 1998-08-05 2000-02-17 Johnson & Johnson Medical Limited Procede de controle de la contamination bacterienne d'une plaie
WO2000065083A2 (fr) * 1999-04-26 2000-11-02 The Procter & Gamble Company Protections periodiques feminines jetables pourvues d'un moyen de detection du sang, en tant que capteur
US6426227B1 (en) * 1999-08-31 2002-07-30 Common Sense Ltd. Method for analyzing secreted bodily fluids
US6478938B1 (en) * 2000-05-24 2002-11-12 Bio Digit Laboratories Corporation Electrochemical membrane strip biosensor

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11578367B2 (en) 2005-04-15 2023-02-14 Becton, Dickinson And Company Diagnosis of sepsis
US10443099B2 (en) 2005-04-15 2019-10-15 Becton, Dickinson And Company Diagnosis of sepsis
GB2430030A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2430029A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2430031A (en) * 2005-09-07 2007-03-14 Ethicon Inc Diagnostic markers of wound infection
GB2430029B (en) * 2005-09-07 2009-04-01 Ethicon Inc Diagnostic markers of wound infection II
GB2430030B (en) * 2005-09-07 2009-04-01 Ethicon Inc Diagnostic markers of wound infection III
US8012698B2 (en) 2007-03-30 2011-09-06 Systagenix Wound Management (Us), Inc. Diagnostic markers of wound infection
GB2447865A (en) * 2007-03-30 2008-10-01 Ethicon Inc Diagnostic markers of wound infection
WO2008119974A1 (fr) * 2007-03-30 2008-10-09 Systagenix Wound Management Ip Co. B.V. Marqueurs diagnostiques d'infection de plaie
WO2009066075A3 (fr) * 2007-11-20 2009-09-03 Convatec Technologies Inc Marqueurs de diagnostic d'une infection de lésion
US10739352B2 (en) 2007-11-20 2020-08-11 Convatec Technologies Inc. Diagnosis and treatment of wound infection with procalcitonin as diagnostic marker
JP2011503631A (ja) * 2007-11-20 2011-01-27 コンバテック・テクノロジーズ・インコーポレイテッド 創傷感染の診断マーカー
WO2009066075A2 (fr) * 2007-11-20 2009-05-28 Convatec Technologies Inc Marqueurs de diagnostic d'une infection de lésion
US10221453B2 (en) 2008-04-03 2019-03-05 Becton, Dickinson And Company Advanced detection of sepsis
US9885084B2 (en) 2008-04-03 2018-02-06 Becton, Dickinson And Company Advanced detection of sepsis
US9708661B2 (en) 2008-04-03 2017-07-18 Becton, Dickinson And Company Advanced detection of sepsis
WO2009122188A3 (fr) * 2008-04-04 2009-12-23 Axis-Shield Diagnostics Ltd Procédé de contrôle d'infection de plaie
WO2009122188A2 (fr) * 2008-04-04 2009-10-08 Axis-Shield Diagnostics Ltd Procédé de contrôle d'infection de plaie
WO2013026999A1 (fr) 2011-08-19 2013-02-28 Pulse Innovate Ltd Système de gestion de plaies
EP3901277A1 (fr) 2020-04-24 2021-10-27 Paul Hartmann AG Procédé et dispositif pour évaluer l'état d'une plaie d'un patient
EP3901276A1 (fr) 2020-04-24 2021-10-27 Paul Hartmann AG Procédé et dispositif pour évaluer l'état d'une plaie d'un patient
WO2021214068A1 (fr) 2020-04-24 2021-10-28 Paul Hartmann Ag Procédé et dispositif d'évaluation de l'état d'une plaie chez un patient
WO2021214259A1 (fr) 2020-04-24 2021-10-28 Paul Hartmann Ag Procédé et dispositif d'évaluation de l'état d'une plaie chez un patient

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