| 1. |
- Wennerås, Christine, 1963, et al.
(författare)
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Distinct Inflammatory Mediator Patterns Characterize Infectious and Sterile Systemic Inflammation in Febrile Neutropenic Hematology Patients
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. Methods: In this prospective study, febrile (>38 degrees C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested. Results: A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. Conclusions: It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications.
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| 2. |
- Krut, Jan Jessen, et al.
(författare)
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Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.
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| 3. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid biomarkers in cardiac arrest survivors.
- 2014
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 85:2, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid β (Aβ) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA).
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| 4. |
- Tillander, Jonatan, 1975, et al.
(författare)
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Osseointegrated titanium implants for limb prostheses attachments: infectious complications.
- 2010
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Ingår i: Clinical orthopaedics and related research. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1132 .- 0009-921X. ; 468:10, s. 2781-2788
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of osseointegration involves direct contact between titanium implant and bone. This transcutaneous prosthetic system for amputees is intended to assure stable long-term fixation. Most metal transcutaneous implants have failed, primarily owing to infection. QUESTIONS/PURPOSES: We determined the frequency and describe the presentation of infectious complications with this novel method. We also evaluated the bacterial flora at the skin-penetration area and its relation to the development of local and implant-related infection. PATIENTS AND METHODS: We prospectively followed 39 patients with arm and leg amputations fitted with transcutaneous osseointegrated titanium implants a mean of 56 months earlier (range, 132-133 months). There were 33 femoral, one tibial, four ulnar, four radial, and three humeral implants. Patients were selected during a 6-month period in 2005 and identically reevaluated after 3 years. Implant infection was defined as definite, probable, or possible based on clinical, radiologic, and microbiologic evidence. RESULTS: The frequency of implant infection was 5% at inclusion and 18% at followup. One patient with infection recovered owing to antibiotic treatment and another patient had the implant removed. Most implant infections had low infectious activity, and in five of the seven patients with infections, prosthetic use was not affected. The most common bacteria in superficial and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci. CONCLUSIONS: Despite frequent colonization around the skin-implant interface by potentially virulent bacteria such as Staphylococcus aureus and bacteria associated with biomedical device infections such as coagulase-negative staphylococci, this titanium implant system for bone-anchored prostheses caused few infections leading to disability or implant removal. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
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| 5. |
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| 6. |
- Bremell, Daniel, 1978, et al.
(författare)
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Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
- 2013
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
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| 7. |
- Bremell, Daniel, 1978, et al.
(författare)
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Clinical characteristics and cerebrospinal fluid parameters in patients with peripheral facial palsy caused by Lyme neuroborreliosis compared with facial palsy of unknown origin (Bell's palsy).
- 2011
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Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Bell's palsy and Lyme neuroborreliosis are the two most common diagnoses in patients with peripheral facial palsy in areas endemic for Borrelia burgdorferi. Bell's palsy is treated with corticosteroids, while Lyme neuroborreliosis is treated with antibiotics. The diagnosis of Lyme neuroborreliosis relies on the detection of Borrelia antibodies in blood and/or cerebrospinal fluid, which is time consuming. In this study, we retrospectively analysed clinical and cerebrospinal fluid parameters in well-characterised patient material with peripheral facial palsy caused by Lyme neuroborreliosis or Bell's palsy, in order to obtain a working diagnosis and basis for treatment decisions in the acute stage. METHODS: Hospital records from the Department of Infectious Diseases, Sahlgrenska University Hospital, for patients with peripheral facial palsy that had undergone lumbar puncture, were reviewed. Patients were classified as Bell's palsy, definite Lyme neuroborreliosis, or possible Lyme neuroborreliosis, on the basis of the presence of Borrelia antibodies in serum and cerebrospinal fluid and preceding erythema migrans. RESULTS: One hundred and two patients were analysed; 51 were classified as Bell's palsy, 34 as definite Lyme neuroborreliosis and 17 as possible Lyme neuroborreliosis. Patients with definite Lyme neuroborreliosis fell ill during the second half of the year, with a peak in August, whereas patients with Bell's palsy fell ill in a more evenly distributed manner over the year. Patients with definite Lyme neuroborreliosis had significantly more neurological symptoms outside the paretic area of the face and significantly higher levels of mononuclear cells and albumin in their cerebrospinal fluid. A reported history of tick bite was uncommon in both groups. CONCLUSIONS: We found that the time of the year, associated neurological symptoms and mononuclear pleocytosis were strong predictive factors for Lyme neuroborreliosis as a cause of peripheral facial palsy in an area endemic for Borrelia. For these patients, we suggest that ex juvantibus treatment with oral doxycycline should be preferred to early corticosteroid treatment.
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| 8. |
- Bremell, Daniel, 1978, et al.
(författare)
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Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review.
- 2011
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Ingår i: Journal of medical case reports. - : Springer Science and Business Media LLC. - 1752-1947. ; 5:465
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Lyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV) -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth case Case presentations: We present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis. CONCLUSION: Given the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with oral doxycycline with a good outcome, further proving the efficacy of this regime.
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| 9. |
- Brink, Magnus, 1960, et al.
(författare)
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A series of severe necrotising soft-tissue infections in a regional centre in Sweden
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:7, s. 882-890
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Tidskriftsartikel (refereegranskat)abstract
- Background: Necrotising soft-tissue infections (NSTIs) are rare conditions with high morbidity and mortality. Patients with NSTIs are often transferred to tertiary hospitals, but the question of whether the potential benefits of highly specialised care outweigh the risks associated with inter-hospital transfers has been raised. Methods: Prospective study including all patients with NSTIs treated at the intensive care unit at Sahlgrenska University Hospital/East between January 2008 and December 2011. Results: Twenty-nine patients with NSTIs were identified. Their median age was 54 years and 69% were men. Major co-morbidities were present in 45%. Seventeen patients (59%) were referred from other hospitals. Only 33% of the patients were correctly diagnosed or suspected of having NSTIs in the emergency department. Group A Streptococcus was the most common microbiological finding (41%), followed by Enterobacteriaceae (17%). The median time from hospitalisation to the first dose of antibiotics was 6 h and the median time to primary surgery was 16 h. Hyperbaric oxygen therapy was given to 86%, and intravenous immunoglobulin was given in 52% of the cases. The 30-day mortality was 14% (4/29). The times to the first dose of antibiotics, intensive care unit admission and primary surgery did not differ between transferred and directly admitted patients, and there was no difference in outcome between the groups. Conclusions: Patients with NSTIs develop severe local and systemic symptoms and require extremely resource-demanding hospitalisation. Inter-hospital transfer was not associated with a delay in key interventions and could not be identified as a risk factor for adverse outcome.
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| 10. |
- Brink, Magnus, 1960, et al.
(författare)
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Respiratory support during the influenza A (H1N1) pandemic flu in Sweden
- 2012
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 56:8, s. 976-986
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute respiratory insufficiency characterised critically ill patients during the influenza A (H1N1) pandemic 20092010. Detailed understanding of disease progression and outcome in relation to different respiratory support strategies is important. Methods Data collected between August 2009 and February 2010 for a national intensive care unit influenza registry were combined with cases identified by the Swedish Institute for Infectious Disease Control. Results Clinical data was available for 95% (126/136) of the critically ill cases of influenza. Median age was 44 years, and major co-morbidities were present in 41%. Respiratory support strategies were studied among the 110 adult patients. Supplementary oxygen was sufficient in 15% (16), non-invasive ventilation (NIV) only was used in 20% (22), while transition from NIV to invasive ventilation (IV) was seen in 41% (45). IV was initiated directly in 24% (26). Patients initially treated with NIV had a higher arterial partial pressure of oxygen/fraction of oxygen in inspired gas ratio compared with those primarily treated with IV. Major baseline characteristics and 28-day mortality were similar, but 90-day mortality was higher in patients initially treated with NIV 17/67 (25%) as compared with patients primarily treated with IV 3/26 (12%), relative risk 1.2 (95% confidence interval 0.34.0). Conclusions Critical illness because of 2009 influenza A (H1N1) in Sweden was dominated by hypoxic respiratory failure. The majority of patients in need of respiratory support were initially treated with NIV. In spite of less severe initial hypoxemia, initiation of ventilatory support with NIV was not associated with improved outcome.
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