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Sökning: WFRF:(Christensson Bertil)

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1.
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2.
  • Widell, Anders, et al. (författare)
  • Epidemiologic and molecular investigation of outbreaks of hepatitis C virus infection on a pediatric oncology service
  • 1999
  • Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819. ; 130:2, s. 130-134
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite screening of blood donors, hepatitis C virus (HCV) infection can occur in patients who receive multiple transfusions. OBJECTIVE: To clarify mechanisms of nosocomial transmission of HCV. DESIGN: Epidemiologic and molecular analyses of hepatitis C outbreaks. SETTING: Pediatric oncology ward. PATIENTS: Children with cancer. MEASUREMENTS: Epidemiologic analysis, HCV RNA detection, genotyping, and hypervariable region 1 (HVR1) sequencing. RESULTS: Ten cases of infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing of HVR1 revealed three related strains. Despite an overhaul of hygiene procedures, a patient infected with genotype 1b generated nine subsequent infected patients in 1994. Several patients had high virus titers and strongly delayed anti-HCV antibody responses. All had permanent intravenous catheters. Multidose vials used for flushing or treatment had probably been contaminated during periods of overlapping treatment. CONCLUSIONS: Contamination of multidose vials was the most likely mode of HCV transmission; therefore, use of such vials should be restricted. Rigorous adherence to hygiene routines remains essential to preventing transmission of bloodborne infections.
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3.
  • Arendrup, M. C., et al. (författare)
  • Detection of candidaemia in patients with and without underlying haematological disease
  • 2010
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 16:7, s. 855-862
  • Tidskriftsartikel (refereegranskat)abstract
    • P>Diagnosing candidaemia remains difficult despite the development of new diagnostics. We report a direct comparison of three different blood-culture systems and four indirect tests. One hundred and fourteen episodes either with haematological disease and fever despite antibacterials, or with documented invasive candidiasis, were enrolled prospectively. Clinical, para-clinical information and surveillance cultures were obtained. Blood culture was performed using conventional blood-culture bottles, mycosis bottles, and the Isolator 10 lysis centrifugation system. Serum D-arabinitol/L-arabinitol (DA/LA) ratios were determined by gas chromatography mass spectrometry. Antigen, mannan-antigen (Ag) and anti-mannan antibody (Ab) were detected by CandTec, Platelia Candida Ag ELISA and Candida AB/AC/AK kits, respectively. Episodes were classified as proven (n = 24), probable (n = 14), possible (n = 52) or unlikely (n = 24) invasive candidiasis. Candidaemia involved C. albicans (17), C. albicans + C. glabrata (3), C. tropicalis (1) and yeast (1). Mycosis bottles yielded two additional positives and the conventional blood culture yielded one positive not identified by other blood-culture methods. Considering proven and unlikely episodes, respectively, sensitivity and specificity were as follows: mannan-Ag and/or anti-mannan Ab: 83.3%, 78.3%; DA/LA ratio: 41.7%, 86.4%; and CandTec Candida Ag: 66.6%, 70.8%. Lowering the cut-off values to mannan-Ag 0.10 ng/mL and anti-mannan Ab 4 AU/mL, the values were: 100%, 73.9%. Applying the DA/LA ratio to only patients with haematological neutropenia the values were: 75%, 90.5%. Fungal blood culture allowed slightly improved detection of candidaemia. The best indirect test performance was obtained from combined mannan-Ag and anti-mannan Ab detection, especially with lower cut-offs. DA/LA ratio appears to be useful in the context of haematological neutropenia.
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4.
  • Christensson, Bertil, et al. (författare)
  • D-arabinitol--a marker for invasive candidiasis
  • 1999
  • Ingår i: Medical Mycology. - 1460-2709. ; 37:6, s. 391-396
  • Tidskriftsartikel (refereegranskat)abstract
    • The five-carbon sugar alcohol D-arabinitol (DA) is a metabolite of most pathogenic Candida species, in vitro as well as in vivo, and can be determined by gas chromatography or enzymatic analysis. Endogenous DA and L-arabinitol (LA) are present in human body fluids, and serum DA and LA increase in renal dysfunction. In prospective clinical studies, elevated DA/LA or DA/creatine ratios in serum or urine have been found in immunocompromised, usually neutropenic, patients with invasive candidiasis. In addition, positive DA results have been obtained several days to weeks before positive blood cultures, and the normalization of DA levels has been correlated with therapeutic response in both humans and animals. However, to date, only a few prospective studies have been conducted in which adequate analytical methods were used. Thus, further investigation of various patient groups is needed to establish the applicability of the 'arabinitol method' in the diagnostic battery for invasive Candida infections.
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5.
  • Christensson, Bertil, et al. (författare)
  • Diagnosis of invasive candidiasis in neutropenic children with cancer by determination of D-arabinitol/L-arabinitol ratios in urine
  • 1997
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 35:3, s. 636-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Determination of D-arabinitol/L-arabinitol ratios (referred to as D/L-arabinitol ratios) in urine as a tool for the diagnosis of invasive candidiasis was investigated in a prospective study comprising 100 children with cancer. The analyses were made by gas chromatography. Positive D/L-arabinitol ratios were found for 10 of 10 children with confirmed invasive candidiasis, 12 of 23 patients undergoing empiric antifungal chemotherapy, and 4 of 67 children not receiving antifungal treatment. D/L-Arabinitol ratios were positive 3 to 31 days (median, 12 days) before the first culture-positive blood sample was drawn or empiric therapy was initiated. The regular monitoring of D/L-arabinitol ratios in urine holds great promise as a sensitive method for diagnosing invasive candidiasis in immunocompromised children with cancer. Moreover, it may be possible to use an early rise in D/L-arabinitol ratios as a basis for the institution of antifungal chemotherapy and as a means of avoiding unnecessary treatment with potentially toxic antifungal agents.
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6.
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7.
  • Christensson, Bertil, et al. (författare)
  • Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission
  • 2000
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 30:3, s. 585-586
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty-eight cases of hepatitis C virus (HCV) infection were identified in children in a pediatric oncology ward during 2 nosocomial outbreaks. HCV infection spontaneously cleared in 6 patients (21%). Eleven patients with persistent HCV viremia who had malignant diseases in remission after treatment were given a 48-week course of combined therapy with interferon-alpha (5x106 U 3 times weekly) and oral ribavirin (15 mg/kg/d). Seven (64%) of the 11 patients had sustained virological responses 6 and 12 months after cessation of therapy. Side effects were common but generally were mild or moderate.
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8.
  • Eisen, DP, et al. (författare)
  • Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection
  • 2002
  • Ingår i: Diagnostic Microbiology and Infectious Disease. - 1879-0070. ; 42:1, s. 39-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here. (C) 2002 Elsevier Science Inc. All rights reserved.
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9.
  • Gustafsson, Bertil, 1943-, et al. (författare)
  • Cellular expression of MDM2 and p53 in childhood leukemias with poor prognosis
  • 2000
  • Ingår i: Medical and Pediatric Oncology. - 0098-1532 .- 1096-911X. ; 34:2, s. 117-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Previous studies have suggested that altered expression or dysfunction of the tumor suppressor gene p53 or the oncogene MDM2 could indicate disease progression in children with leukemia who would fail to achieve complete remission or who would relapse. While these studies mainly have described aberrations of MDM2 and p53 function at the DNA and mRNA- level, we have examined p53 and MDM2 expression at the protein level. Mutation of the p53 tumor suppressor gene may result in cellular accumulation of the p53 protein, due to prolonged half-life of the abnormal protein. The p53 protein can also be rendered nonfunctional by overexpression of proteins that bind to p53, such as MDM2. Both pathways have been proposed to disrupt cell cycle regulation in humans. Recent studies have shown that increased expressions of MDM2 as well as of p53 can be detected at the protein level in the absence of gene amplification. Procedure. Forty-three bone marrow samples were analyzed immunohistochemically for p53 and MDM2. Twenty-nine bone marrow samples were obtained in children with active, prognostically unfavorable leukemia and MDS. Fourteen bone marrow samples were from children with non- malignant hematological disorders. Results. p53 protein was expressed in 12 patients and MDM2 in 17 patients with leukemia. In the control group MDM2 expression was detected in one child, while p53 was not found in any of the samples. Conclusions. Our findings of p53 or MDM2 positive cells in a majority of children with unfavorable prognostic features suggests that dysfunction of the p53-dependent cell growth control have a role in the development of high risk leukemias.
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11.
  • Hammarström, Helena, et al. (författare)
  • Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients
  • 2018
  • Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:9, s. 623-632
  • Tidskriftsartikel (refereegranskat)abstract
    • We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.
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12.
  • Holmberg, Anna, et al. (författare)
  • Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates
  • 2009
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 15:8, s. 787-795
  • Tidskriftsartikel (refereegranskat)abstract
    • Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45) or from the skin of healthy people (n = 48), was analysed. The majority of isolates from deep infections produced biofilm in a microtitre model of biofilm formation, whereas the skin isolates were poor biofilm producers (p <0.001 for a difference). This indicates a role for biofilm formation in P. acnes virulence. The type distribution, as determined by sequencing of recA, was similar among isolates isolated from skin and from deep infections, demonstrating that P. acnes isolates with different genetic backgrounds have pathogenic potential. The biofilm formed on plastic and on bone cement was analysed by scanning electron microscopy (EM) and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the bacteria and was composed of filamentous as well as more amorphous structures. Interestingly, the presence of human plasma in solution or at the plastic surface inhibits biofilm formation, which could explain why P. acnes primarily infect plasma-poor environments of, for example, joint prostheses and cerebrospinal shunts. This work underlines the importance of biofilm formation in P. acnes pathogenesis, and shows that biofilm formation should be considered in the diagnosis and treatment of invasive P. acnes infections.
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13.
  • Jönsson, Göran, et al. (författare)
  • A case of Mycobacterium goodii prosthetic valve endocarditis in a non-immunocompromised patient: use of 16S rDNA analysis for rapid diagnosis
  • 2012
  • Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mycobacterium goodii is a rare cause of significant infection. M. goodii has mainly been associated with lymphadenitis, cellulitis, osteomyelitis, and wound infection. Case presentation: A case of a 76-year-old Caucasian female is presented. The patient developed a prosthetic valve endocarditis caused by M. goodii. She had also suffered from severe neurological symptoms related to a septic emboli that could be demonstrated as an ischemic lesion found on CT of the brain. Transesophageal echocardiography verified a large vegetation attached to the prosthetic valve. Commonly used blood culture bottles showed growth of the bacteria after 3 days. Conclusions: Although M. goodii is rarely involved in these kinds of severe infections, rapidly growing mycobacteria should be recognized during conventional bacterial investigations and identified by molecular tools such as analysis of 16S rDNA. Species identification of nontuberculous mycobacteria is demanding and is preferably done in collaboration with a mycobacterial laboratory. An early diagnosis provides the opportunity for adequate treatment. In the present case, prolonged antimicrobial treatment and surgery with replacement of the prosthetic valve was successful.
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14.
  • Kahn, Fredrik, et al. (författare)
  • Axillary abscess complicated by venous thrombosis, identification of Streptococcus pyogenes by 16S PCR.
  • 2010
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 48:9, s. 3435-3437
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a case of an axillary abscess with Streptococcus pyogenes complicated by venous thrombosis. Bacterial etiology and typing was obtained by PCR and sequencing of the 16S rRNA and the M-protein genes from abscess material. The bacterium was of M41 serotype and serology indicated that it had expressed pro-coagulant factors.
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15.
  • Kahn, Fredrik, et al. (författare)
  • Heparin-Binding Protein As A Prognostic Biomarker of Sepsis and Disease Severity at The Emergency Department
  • 2019
  • Ingår i: Shock. - 1540-0514. ; 52:6, s. 135-135
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma-levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.DESIGN: Prospective, international multicenter, convenience sample study SETTING:: Four general emergency departments at academic centers in Sweden, Switzerland and Canada.PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: a) respiratory rate >25 breaths per minute; b) heart rate >120 beats per minute; c) altered mental status; d) systolic blood pressure <100 mm Hg; e) oxygen saturation <90% without oxygen; f) oxygen saturation <93% with oxygen; g) reported oxygen saturation <90%.INTERVENTION: None MEASUREMENTS AND MAIN RESULTS:: A total of 524 ED patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a non-infectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 hours, 54 patients (10%) were admitted to an intensive care unit (ICU), and 23 patients (4%) died within 72 hours. For the primary outcome, detection of infected-related organ dysfunction within 72 hours, the AUC for HBP was 0.73 (95% C.I. 0.68-0.78) among all patients and 0.82 (95% C.I. 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 hours) HBP had an AUC of 0.87 (95% C.I. 0.79-0.95) among all patients and 0.88 (95% C.I. 0.77-0.99) among patients confidently adjudicated to either infection or non-infection.CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.
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16.
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17.
  • Karlsson, Ulf, et al. (författare)
  • Human granulocytic ehrlichiosis - A clinical case in Scandinavia
  • 2001
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 33:1, s. 73-74
  • Tidskriftsartikel (refereegranskat)abstract
    • A clinical case of human granulocytic ehrlichiosis in Scandinavia is presented. The patient developed high fever, myalgia, headache and dyspnoea. Doxycycline treatment resulted in a dramatic improvement. Laboratory confirmation Included a fourfold change in anti-Ehrlichia equi IFA titre and a positive PCR confirmed by gene sequence analysis.
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18.
  • Kindeberg, Tina, et al. (författare)
  • Changing Swedish students' attitudes in relation to the Aids epidemic
  • 1994
  • Ingår i: Health Education Research. - 0268-1153. ; 9:2, s. 171-181
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study we have evaluated the knowledge, attitudes and intention to act in relation to HIV/AIDS related issues among Swedish students aged 15–18 years. An intervention group (n = 368) and a comparison group (n = 180) were followed for 2 years between 1989 and 1991. The teachers of the intervention group were obliged to specifically give a continuous and in-depth education while the comparison group received ordinary traditional education. We present the results from questionnaires given to all students before and after the study. There was a significant increase in knowledge of facts in the intervention group, and also changes in attitudes towards, for example, gay people, drug users and HIV infected individuals, in a desirable direction. In sex related issues there was also a desirable change in intention to act, but this was not seen in students' relation to alcohol. No significant changes at all in knowledge, attitudes or intention to act were seen in the comparison group. Our results show that it is indeed possible to influence students' attitudes and intention to act in HIV/AIDS related issues provided teachers start by defining the students' central conceptions and their relation to each other, and promote individual thinking and reflection.
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19.
  • Larsson, Lennart, et al. (författare)
  • Gas chromatographic determination of D-arabinitol/L-arabinitol ratios in urine: a potential method for diagnosis of disseminated candidiasis
  • 1994
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 32:8, s. 1855-1859
  • Tidskriftsartikel (refereegranskat)abstract
    • A gas chromatographic procedure was developed to determine the relative amounts of D- and L-arabinitol in urine. Samples were filtered, diluted, purified through extractions, evaporated, and treated with trifluoroacetic anhydride; the arabinitol derivatives thus obtained were separated on a chiral stationary phase and registered by using an electron-capture detector. Urine samples from a patient with disseminated candidiasis had higher D-arabinitol/L-arabinitol ratios (referred to as D/L-arabinitol ratios)--up to 19.0--than samples from 96 study individuals with no signs of deep Candida infections (range, 1.1 to 4.5). D/L-Arabinitol ratios in urine samples from hospitalized patients without Candida infections were slightly higher than those in samples from healthy individuals; ratios in urine from children were slightly higher than those in adult urine samples. The D/L-arabinitol ratios in several urine samples culture positive for Candida albicans, but from patients without symptoms of disseminated candidiasis, did not differ from those in the urine of healthy individuals. The described gas chromatographic method is straightforward and can be implemented clinically to determine urine D/L-arabinitol ratios as a means of diagnosing disseminated candidiasis.
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21.
  • Linder, Adam, et al. (författare)
  • Erysipelas Caused by Group A Streptococcus Activates the Contact System and Induces the Release of Heparin-Binding Protein.
  • 2010
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 130, s. 1365-1372
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial skin infections, such as erysipelas or cellulitis, are characterized by fever and a painful erythematous rash. Despite the high prevalence of these infections, little is known about the underlying pathogenic mechanisms. This is partly due to the fact that a bacterial diagnosis is often difficult to attain. To gain insight into the pathogenesis of erysipelas, we investigated the samples obtained from infected and noninfected areas of skin from 12 patients with erysipelas. Bacterial cultures, detection of specific streptococcal antibodies in convalescent sera, and immunohistochemical analyses of biopsies indicated group A streptococcal etiology in 11 of the 12 patients. Also, electron micrographs of erythematous skin confirmed the presence of group A streptococcal cells and showed a limited solubilization of the surface-attached M protein. Degradation of high-molecular-weight kininogen and upregulation of the bradykinin-1 receptor in inflamed tissues indicated activation of the contact system in 11 patients. Analyses of release of the vasoactive heparin-binding protein (HBP) showed increased levels in the infected as compared with the noninfected areas. The results suggest that group A streptococci induce contact activation and HBP release during skin infection, which likely contribute to the symptoms seen in erysipelas: fever, pain, erythema, and edema.Journal of Investigative Dermatology advance online publication, 28 January 2010; doi:10.1038/jid.2009.437.
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22.
  • Linder, Adam, et al. (författare)
  • Heparin-binding protein: A diagnostic marker of acute bacterial meningitis
  • 2011
  • Ingår i: Critical Care Medicine. - 0090-3493. ; 39:4, s. 812-817
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. OBJECTIVE: In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis. DESIGN: One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed. SETTING AND PATIENTS: Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters. CONCLUSION: Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.
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23.
  • Linder, Adam, et al. (författare)
  • Heparin-binding protein: A diagnostic marker of acute bacterial meningitis. : a diagnostic marker of acute bacterial meningitis
  • 2011
  • Ingår i: Critical Care Medicine. - 1530-0293. ; 39:4, s. 812-817
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis.OBJECTIVE: In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis.DESIGN: One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed.SETTING AND PATIENTS: Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters.CONCLUSION: Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.
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24.
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25.
  • Linder, Adam, et al. (författare)
  • Heparin-binding protein: an early marker of circulatory failure in sepsis.
  • 2009
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 49:7, s. 1044-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The early detection of circulatory failure in patients with sepsis is important for successful treatment. Heparin-binding protein (HBP), released from activated neutrophils, is a potent inducer of vascular leakage. In this study, we investigated whether plasma levels of HBP could be used as an early diagnostic marker for severe sepsis with hypotension. METHODS: A prospective study of 233 febrile adult patients with a suspected infection was conducted. Patients were classified into 5 groups on the basis of systemic inflammatory response syndrome criteria, organ failure, and the final diagnosis. Blood samples obtained at enrollment were analyzed for the concentrations of HBP, procalcitonin, interleukin-6, lactate, C-reactive protein, and the number of white blood cells. RESULTS: Twenty-six patients were diagnosed with severe sepsis and septic shock, 44 patients had severe sepsis without septic shock, 100 patients had sepsis, 43 patients had an infection without sepsis, and 20 patients had an inflammatory response caused by a noninfectious disease. A plasma HBP level > or = 15 ng/mL was a better indicator of severe sepsis (with or without septic shock) than any other laboratory parameter investigated (sensitivity, 87.1%; specificity, 95.1%; positive predictive value, 88.4%; negative predictive value, 94.5%). Thirty-two of the 70 patients with severe sepsis were sampled for up to 12 h before signs of circulatory failure appeared, and in 29 of these patients, HBP plasma concentrations were already elevated. CONCLUSION: In febrile patients, high plasma levels of HBP help to identify patients with an imminent risk of developing sepsis with circulatory failure.
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26.
  • Linder, Adam, et al. (författare)
  • Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department
  • 2015
  • Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS and WILKINS. - 0090-3493 .- 1530-0293. ; 43:11, s. 2378-2386
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (greater than 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.
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27.
  • Linder, Adam, et al. (författare)
  • Human antibody response towards the pneumococcal surface proteins PspA and PspC during invasive pneumococcal infection.
  • 2007
  • Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 25:2, s. 341-345
  • Tidskriftsartikel (refereegranskat)abstract
    • gG antibodies against pneumococcal surface protein A, family 1 (PspAl) and family 2 (PspA2), protein C (PspC), and protein Hic were investigated in 41 patients with invasive pneumococcal disease. Pre-existing antibody levels against the four pneumococcal proteins were not significantly different from those found in 40 patients with non-pneumococcal bacteremia or 80 healthy controls. However, during convalescense a strong immune response developed especially against PspA, and there was a high degree of cross-reactivity between PspA-and PspC-antibodies. Our findings on immunogenicity and cross-reactivity suggest that in a future pneumococcal protein based vaccine, only a limited number of proteins could be sufficient.
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28.
  • Mellhammar, Lisa, et al. (författare)
  • Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching
  • 2021
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • One can falsely assume that it is well known that bacteremia is associated with higher mortality in sepsis. Only a handful of studies specifically focus on the comparison of culture-negative and culture-positive sepsis with different conclusions depending on study design. The aim of this study was to describe outcome for critically ill patients with either culture-positive or -negative sepsis in a clinical review. We also aimed to identify subphenotypes of sepsis with culture status included as candidate clinical variables. Out of 784 patients treated in intensive care with a sepsis diagnosis, blood cultures were missing in 140 excluded patients and 95 excluded patients did not fulfill a sepsis diagnosis. Of 549 included patients, 295 (54%) had bacteremia, 90 (16%) were non-bacteremic but with relevant pathogens detected and in 164 (30%) no relevant pathogen was detected. After adjusting for confounders, 90-day mortality was higher in bacteremic patients, 47%, than in non-bacteremic patients, 36%, p = 0.04. We identified 8 subphenotypes, with different mortality rates, where pathogen detection in microbial samples were important for subphenotype distinction and outcome. In conclusion, bacteremic patients had higher mortality than their non-bacteremic counter-parts and bacteremia is more common in sepsis when studied in a clinical review. For reducing population heterogeneity and improve the outcome of trials and treatment for sepsis, distinction of subphenotypes might be useful and pathogen detection an important factor.
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29.
  • Mellhammar, Lisa, et al. (författare)
  • NEWS2 is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department
  • 2019
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75-0.83) and 0.70 (95% CI 0.65-0.74), than qSOFA, AUC 0.70 (95% CI 0.66-0.75) and 0.62 (95% CI 0.57-0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.
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30.
  • Mellhammar, Lisa, et al. (författare)
  • Public Awareness of Sepsis Is Low in Sweden.
  • 2015
  • Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 2:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Sepsis is a serious and common condition with high mortality and morbidity. The public awareness, knowledge, and perception of sepsis in Sweden are unknown. Methods. A survey was performed using an online interview distributed to adults, aged 18-74, between March 6 and 9, 2015. Results. A total of 1001 people responded to the survey. Twenty-one percent of participants had heard of sepsis, whereas more than 86% had heard of each of the other conditions listed; for example, stroke (95%), chronic obstructive pulmonary disease (COPD) (95%), and leukemia (92%). Of those who had heard of sepsis, 93% responded that it is an infection or blood poisoning in an open question. The respondents who had heard of each disease estimated its mortality. For sepsis, the mortality was estimated at an average of 30%, which was at the same level as estimated mortalities for prostate and breast cancer but lower than for stroke, COPD, and leukemia. Conclusions. The awareness and knowledge of sepsis is low. The mortality for sepsis is not as overestimated as for many other diseases. The lack of awareness of sepsis might be a target to improve the outcome for sepsis patients by reducing the prehospital delay and hence enable early interventions. An increased general awareness might also raise interest for funding for research in this area and for its priority in healthcare support.
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31.
  • Mellhammar, Lisa, et al. (författare)
  • Scores for sepsis detection and risk stratification – construction of a novel score using a statistical approach and validation of RETTS
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background To allow early identification of patients at risk of sepsis in the emergency department (ED), a variety of risk stratification scores and/or triage systems are used. The first aim of this study was to develop a risk stratification score for sepsis based upon vital signs and biomarkers using a statistical approach. Second, we aimed to validate the Rapid Emergency Triage and Treatment System (RETTS) for sepsis. RETTS combines vital signs with symptoms for risk stratification. Methods We retrospectively analysed data from two prospective, observational, multicentre cohorts of patients from studies of biomarkers in ED. A candidate risk stratification score called Sepsis Heparin-binding protein-based Early Warning Score (SHEWS) was constructed using the Least Absolute Shrinkage and Selector Operator (LASSO) method. SHEWS and RETTS were compared to National Early Warning Score 2 (NEWS2) for infection-related organ dysfunction, intensive care or death within the first 72h after admission (i.e. sepsis). Results 506 patients with a diagnosed infection constituted cohort A, in which SHEWS was derived and RETTS was validated. 435 patients constituted cohort B of whom 184 had a diagnosed infection where both scores were validated. In both cohorts (A and B), AUC for infection-related organ dysfunction, intensive care or death was higher for NEWS2, 0.80 (95% CI 0.76–0.84) and 0.69 (95% CI 0.63–0.74), than RETTS, 0.74 (95% CI 0.70–0.79) and 0.55 (95% CI 0.49–0.60), p = 0.05 and p <0.01, respectively. SHEWS had the highest AUC, 0.73 (95% CI 0.68–0.79) p = 0.32 in cohort B. Conclusions Even with a statistical approach, we could not construct better risk stratification scores for sepsis than NEWS2. RETTS was inferior to NEWS2 for screening for sepsis.
  •  
32.
  • Mellhammar, Lisa, et al. (författare)
  • Sepsis Incidence : A Population-Based Study
  • 2016
  • Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 3:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although sepsis is a major health problem, data on sepsis epidemiology are scarce. The aim of this study was to assess the incidence of sepsis, based on clinical findings in all adult patients treated with intravenous antibiotic in all parts of all hospitals in an entire population.METHODS: This is a retrospective chart review of patients ≥18 years, living in 2 regions in Sweden, who were started on an intravenous antibiotic therapy on 4 dates, evenly distributed over the year of 2015. The main outcome was the incidence of sepsis with organ dysfunction. The mean population ≥18 years at 2015 in the regions was 1275753. Five hundred sixty-three patients living in the regions were started on intravenous antibiotic treatment on the dates of the survey. Patients who had ongoing intravenous antibiotic therapy preceding the inclusion dates were excluded, if sepsis was already present.RESULTS: Four hundred eighty-two patients were included in the study; 339 had a diagnosed infection, of those, 96 had severe sepsis according to the 1991/2001 sepsis definitions, and 109 had sepsis according to the sepsis-3. This is equivalent to an annual incidence of traditional severe sepsis of 687/100000 persons (95% confidence interval [CI], 549-824) or according to the sepsis-3 definition of 780/100000 persons (95% CI, 633-926). Seventy-four patients had sepsis according to both definitions.CONCLUSIONS: The incidence of sepsis with organ dysfunction is higher than most previous estimates independent of definition. The inclusion of all inpatients started on intravenous antibiotic treatment of sepsis in a population makes an accurate assessment of sepsis incidence possible.
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33.
  • Mellhammar, Lisa, et al. (författare)
  • Sepsis - vår tids okända folksjukdom
  • 2015
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112:47
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
34.
  • Naver, Lars, et al. (författare)
  • Broad spectrum of time of detection, primary symptoms and disease progression in infants with HIV-1 infection
  • 2001
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 20:3, s. 159-166
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between time of HIV-1 detection, appearance of symptoms and disease progression was studied in all 24 HIV-1-infected infants from a cohort of 117 children who were born to HIV-1-infected mothers and monitored from birth. HIV isolation from plasma and mononuclear cells, HIV-1 DNA PCR (polymerase chain reaction) and, retrospectively, a quantitative assay for HIV-1 RNA were used for virus detection. Two infants possibly exhibited a symptomatic primary HIV infection. More children with than without symptoms during the first year of life progressed to immunological class 3 (P=0.013) and to AIDS or death (P=0.003) during follow-up. HIV-1 was detected within 4 days of age in 4 of 16 infants: 3 of them became symptomatic within 1 year, as did 6 of the remaining 12 infants (not statistically significant). All four infants in whom virus was detected within 4 days of age progressed to severe immunosuppression, compared to 6 of 14 in whom the virus detection test was initially negative prior to the first positive result (n.s.). Two children with previous repeatedly negative HIV detection tests were diagnosed with HIV-1 infection at 8 and 9 months, respectively. Repeated blood sampling is needed for the diagnosis of HIV-1 infection in perinatally exposed infants, and virus detection tests for exclusion of HIV-1 infection must be used with caution.
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35.
  • Navér, Lars, et al. (författare)
  • Long-term pattern of HIV-1 RNA load in perinatally infected children
  • 1999
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 31:4, s. 337-343
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to describe the natural history of HIV-1 RNA load in vertically HIV-1-infected children. HIV-1 RNA in 156 plasma or serum samples (1-14, median 4 from each child) from 32 vertically HIV-1-infected children was detected with the NASBA® technique (Organon Teknika, The Netherlands). Twenty-one children were prospectively followed from birth, and 11 were identified and included at the age of 7-89 (median 61) months. The highest numbers of HIV-1 RNA copies were seen at 1.5-3 months of age. A quadratic curve model showed a reduction of HIV-1 RNA with increasing age up to approximately 8 years, and thereafter increasing numbers, p(age) = 0.002, p(age2) = 0.008, This pattern was not typical for individual children in whom a great variation in HIV-1 RNA numbers was seen over time. The interval from birth to the first HIV-1 RNA peak ranged from 1.5 months to more than 2 years. The HIV-1 RNA levels remained relatively high and fluctuating over the years in symptomatic as well as in long-term symptomatic children. This makes HIV-1 RNA determination in children more difficult to use than in adults, as the only tool for prediction of disease progression and for initiation of therapy.
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36.
  • Rasmussen, Magnus, et al. (författare)
  • Lactococcus garvieae endocarditis presenting with subdural haematoma.
  • 2014
  • Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactococcus garvieae is a rare cause of infective endocarditis (IE) in humans and the bacterium can easily be misidentified. Intracranial haemorrhage often occurs in conjunction with IE, but subdural haemorrhage (SDH) is very rarely encountered.
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37.
  • Sendi, P, et al. (författare)
  • Group B streptococcus in prosthetic hip and knee joint-associated infections
  • 2011
  • Ingår i: Journal of Hospital Infection. - : Saunders Elsevier. - 0195-6701 .- 1532-2939. ; 79:1, s. 64-69
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of invasive group B streptococcus (GBS) infections in non-pregnant adults is increasing. Little is known about GBS in periprosthetic joint infections (PJIs). We aimed to analyse the clinical presentation of GBS PJI and its treatment in association with the outcome. The characteristics of 36 GBS PJIs collected from 10 centres were investigated. In 34 episodes, follow-up examination of ≥ 2 years was available, allowing treatment and outcome analysis. Most infections (75%) occurred ≥ 3 months after implantation. Most patients (91%) had at least one comorbidity; 69% presented with acute symptoms and 83% with damaged periprosthetic soft tissue. In 20 of 34 episodes debridement and retention of implant was attempted, but in five of these the prosthesis was ultimately removed. Hence, in 19 (56%) episodes, the implant was removed, including 14 immediate removals. In four episodes the removal was permanent. Penicillin derivatives and clindamycin were the most common antimicrobials administered (68%). In 94% the infection was cured, and in 82% functional mobility preserved. Debridement with implant retention was successful if the duration of symptoms was short, the prosthesis stable, and the tissue damage minor (10/10 vs 3/10 episodes, P = 0.003). Surgery that complied with a published algorithm was associated with a favourable outcome (P = 0.049).
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38.
  • Sigmundsdottir, Gudrun, et al. (författare)
  • Clinical experience of urine D-arabinitol/L-arabinitol ratio in the early diagnosis of invasive candidiasis in paediatric high risk populations
  • 2007
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 39:2, s. 146-151
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2 prospective studies, we previously reported on the early and accurate diagnosis of invasive candidiasis by determining the D-arabinitol/L-arabinitol (DA/LA) ratio in urine in neutropenic children with cancer at the paediatric oncology unit (POU) and in premature infants at the neonatal intensive care unit (NICU) at our hospital. In this retrospective study at the same units, we report how the DA/LA assay was implemented in clinical practice immediately after the prospective study periods. We found that, in the POU, the recommendation of regularly monitoring urine DA/LA ratios in patients at risk and considering antifungal therapy in the case of elevated ratios had been followed. A significant decrease in the incidence of culture positive invasive candidiasis may have been attributed to the introduction of the DA/LA assay. At the NICU, where the DA/LA assay was recommended only as an adjunct to other diagnostic tools, morbidity in invasive candidiasis remained unchanged. While regular monitoring of the urine DA/LA ratio probably facilitates the early detection of invasive candidiasis in paediatric oncology, it remains to be determined if the test can be used in a similar way in neonatal intensive care.
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39.
  • Sigmundsdottir, Gudrun, et al. (författare)
  • Urine D-arabinitol/L-arabinitol ratio in diagnosis of invasive candidiasis in newborn infants
  • 2000
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 38:8, s. 3039-3042
  • Tidskriftsartikel (refereegranskat)abstract
    • Infants treated in neonatal intensive care units suffer an increased risk for invasive candidiasis, but the diagnosis is sometimes difficult. D-arabinitol is a metabolite of most pathogenic Candida species. An elevated urine D-arabinitol/L-arabinitol (DA/LA) ratio is a sensitive sign of invasive candidiasis in children with cancer, but the method has not been previously evaluated for newborn infants. We therefore enrolled 117 infants in a neonatal intensive care unit, and 411 urine samples were obtained on filter paper. The DA/LA ratio was measured by gas chromatography-mass spectrometry. For 81 infants with no suspicion of superficial or invasive candidiasis, the urine DA/LA ratio was 2.7 +/- 0.7 (mean +/- standard deviation [SD]). The upper cutoff level was set at 4.8 (mean plus 3 SD). Of 22 infants with mucocutaneous candidiasis and not given systemic antifungal treatment, two had elevated DA/LA ratios, which normalized after removal of intravascular catheters. Eight other infants were given empiric antifungal treatment but had negative cultures; five of these had repeatedly elevated DA/LA ratios. Six infants with culture-positive invasive candidiasis all had one or more samples with elevated ratios. For seven infants, three with suspected and four with confirmed invasive candidiasis (for which follow-up samples were available), ratios normalized during antifungal treatment. In conclusion, urine DA/LA ratio determination is a rapid test and can be used for newborns. It is possibly more sensitive than fungal blood cultures in the diagnosis of invasive candidiasis and can also be used for monitoring the effect of antifungal treatment.
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40.
  • Sjöqvist, Axel S.L. 1990, et al. (författare)
  • Geochronology of the Norra Kärr alkaline complex, southern Sweden
  • 2014
  • Ingår i: 31st Nordic Geological Winter Meeting.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The Norra Kärr alkaline complex is a small intrusion of agpaitic nepheline syenite, located approximately 10 km north of Grän- na, southern Sweden, that is being explored for REE and Zr. Agpaitic nepheline syenites per definition do not contain simple Zr minerals like zircon and baddeleyite, despite generally high Zr contents (up to 1–2 wt.% ZrO2). Instead, Zr is mainly hosted in rock-forming complex Na-Ca-Zr silicate minerals such as members of the catapleiite, eudialyte, rosenbuschite, and wöhlerite groups. U-Pb zircon geochronology is thus highly impeded by the agpaitic nature. We established a new, reliable igneous age for the Norra Kärr alkaline complex at 1489±8 Ma (MSWD = 0.95) by dating zircons (U-Pb) in the country rocks that were affected by the magmatism-related alkaline alteration (fenitisation) by LA-MC-ICP-MS. Zircons from a satellite body of non-agpaitic syenite gave intercept ages within error of the age of fenitisation. This is an improvement upon an imprecise whole-rock Rb-Sr age of 1545±61 Ma (Blaxland 1977; Welin 1980). The non-fenitised country granite itself is dated at 1781±8 Ma (MSWD = 0.59), and thus belongs to the TIB1 (1.81–1.76 Ga) episode of the Transscandinavian Igneous Belt (TIB). Rare zircon xenocrysts extracted from the nepheline syenite show ages corresponding to 1.5 Ga lower crustal intrusives (rapakivi?), TIB, Svecofennian, and one Archaean zircon, which suggests the possibility for a remnant of Archaean basement below the TIB. There has historically been a vivid discussion about wheth- er or not Norra Kärr has been deformed and metamorphosed. New Ar-Ar step heating ages on sodic amphibole from Norra Kärr and muscovite and biotite from the country rocks give plateau ages at 1.1 Ga and 0.94 Ga, which correspond to ages derived for Sveconorwegian shear zones in the area. Together with textural and crystal chemical evidence, these ages make a compelling argument for some form of Sveconorwegian overprint of the Norra Kärr alkaline complex.
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41.
  • Stjärne Aspelund, Anna, et al. (författare)
  • Heparin-binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients
  • 2018
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 18:2, s. 444-452
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL-1, and IL-8 were the best diagnostic markers of infection with area under the receiver-operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL-1, and IL-8 could be useful diagnostic markers of pulmonary infection in lung-transplanted patients. This prospective study on bronchoalveolar fluid from lung transplant recipients suggests that heparin-binding protein, IL-1beta, and IL-8 are useful biomarkers for the detection of pulmonary infection.
  •  
42.
  • Stjärne Aspelund, Anna, et al. (författare)
  • Microbiological findings in bronchoalveolar lavage fluid from lung transplant patients in Sweden
  • 2018
  • Ingår i: Transplant Infectious Disease. - : Wiley. - 1398-2273 .- 1399-3062. ; 20:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough. Methods: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx). Differences in microbiological findings depending of concomitant signs of infection and background factors were assessed. Results: A total of 470 bronchoscopies from 126 patients were evaluated. Sixty-two percent (n = 293) of BALF samples had positive microbiological finding(s). Forty-six percent (n = 217) had bacterial growth, 29% (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of BALF samples (n = 181), a single microbe was found, whereas a combination of bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most common microbiological findings were Candida albicans, Pseudomonas aeruginosa and coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients, respectively). Microbiological findings were similar in BALF from patients with and without signs of lung infection and the frequency of multidrug resistant (MDR) bacteria was low. No significant association was found between background factors and time to first lung infection. Conclusion: This study gives important epidemiologic insights and reinforces that microbiological findings have to be evaluated in the light of clinical symptoms and endobronchial appearance in the assessment of lung infections in lung transplant patients.
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43.
  •  
44.
  • Tevell, Staffan, 1975-, et al. (författare)
  • Handläggning av infektioner vid ortopediska implantat en utmaning för vården : [Treatment of orthopedic implant-associated infections]
  • 2019
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 116:43
  • Forskningsöversikt (refereegranskat)abstract
    • The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed. The study group emphasizes that implant associated infections are challenging and requires multidisciplinary cooperation, including, but not limited to, specialists in orthopedic surgery, infectious diseases, clinical microbiology and radiology for optimal treatment results. All aspects of the clinical management are equally important; selecting the optimal antibiotic prophylaxis in arthroplasty as well as fracture surgery, early diagnosis of infection, adequate treatment, follow-up, and finally a structured evaluation of outcome. Profound and updated knowledge of treatment of biofilm related infection is necessary to achieve optimal results in patients with implant-associated infections. Future challenges include improved decision support for combining surgical treatment with selection of proper antibiotics, as well as management of antibiotic resistance, drug-drug interactions and adverse effects of antibiotic treatment.
  •  
45.
  •  
46.
  • Thompson, Olof, et al. (författare)
  • A population-based study on the treatment and outcome of enterococcal prosthetic joint infections. : A consecutive series of 55 cases.
  • 2019
  • Ingår i: Journal of Bone and Joint Infection. - : Copernicus GmbH. - 2206-3552. ; 4:6, s. 285-291
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM Enterococci cause 2-11% of all prosthetic joint infections (PJI) and are generally considered difficult to treat. However, study-results are not consistent. In this study we present a population-based case series of 55 cases with enterococcal PJI, investigating treatment and outcome, as well as describing the affected patient population regarding demography and co-morbidities. METHODS We identified all enterococcal PJIs in the Region of Skåne, Sweden, during a five-year period (2011-2015) and reviewed the patients' medical records. RESULTS Fifty-five enterococcal PJIs were found. Enterococcus faecalis was the most frequently isolated species (84%), and poly-microbial infections were common (64%). Treatment with intention to cure was given to 43 (78%) cases. Debridement with retention of the implant and antibiotics (DAIR) was the most common surgical treatment strategy (71%), with a cure-rate of 72%. Overall cure-rate was 67%, and in cases where cure was intended, this was achieved in 80%. CONCLUSIONS When cure is aimed for, the prognosis for enterococcal PJI is not so poor, and DAIR treatment can provide adequate results in many cases.
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47.
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48.
  • Åkesson, Per, et al. (författare)
  • IdeS, a highly specific immunoglobulin G (IgG)-cleaving enzyme from Streptococcus pyogenes, is inhibited by specific IgG antibodies generated during infection
  • 2006
  • Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 74:1, s. 497-503
  • Tidskriftsartikel (refereegranskat)abstract
    • IdeS, a recently discovered cysteine proteinase secreted by the important human pathogen Streptococcus pyogenes, interferes with phagocytic killing by specifically cleaving the heavy chain of immunoglobulin G. The fact that the enzyme targets one of the key molecules of the adapted immune response raised the question of whether an antibody response against IdeS could inhibit, i.e., neutralize, enzyme activity. Paired acute- and convalescent-phase serum samples from patients with pharyngotonsillitis (n = 10), bacteremia (n = 7), and erysipelas (n = 4) were analyzed. Antibodies with the ability to neutralize IdeS enzymatic activity were already found in two-thirds of acute-phase sera. However, patients who seroconverted to IdeS, in particular patients with pharyngotonsillitis and erysipelas, developed specific antibodies during convalescence with an increased capability to efficiently neutralize the enzymatic activity of IdeS. Also, the presence of neutralizing antibodies decreased the ability of IdeS to mediate bacterial survival in human immune blood. In patients with bacteremia, several acute-phase sera contained neutralizing antibodies, but no correlation was found to severity or outcome of invasive infections. Still, the fact that the human immune response targets the enzymatic activity of IdeS supports the view that the enzyme plays an important role during streptococcal infection.
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49.
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