Kristian Kofoed

Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

IntroductionAccurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination.MethodsThis prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers.ResultsA total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers.ConclusionCombining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics.Trial registrationNCT 00389337

Syphilis and human immunodeficiency virus (HIV)-1 coinfection : Influence on CD4 T-cell count, HIV-1 viral load, and treatment response

Objectives: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. Study Design: Cases of syphilis diagnosed during 1 year in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. Results: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis (mean 106 cells/mm3, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm3 and −0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25 treated with doxycycline were the same. Conclusion: Syphilis was associated with a decrease in CD4 cell counts and an increase in HIV-RNA levels that both improved after treatment of syphilis.

Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor

Better outcomes in patients suspected of community-acquired infections requires the optimal and timely assessment of disease severity at the point of first contact with the health care system, which is typically in the emergency department. This study was conducted using a previously described, prospectively collected cohort of patients with systemic inflammatory response syndrome (SIRS) that were admitted to an emergency department and a department of infectious diseases at a university hospital. Plasma samples were collected and disease severity scores calculated upon admission. A multiplex immunoassay and a newly developed enzyme-linked immunosorbent assay (ELISA)-based assay were used to measure the soluble urokinase-type plasminogen activator receptor, soluble triggering receptor expressed on myeloid cells-1, and macrophage migration inhibitory factor. The area under the receiver operating characteristic (ROC) curve for the prediction of 30- and 180-day mortality was used to compare the performance of the markers and the models. A total of 151 patients were eligible for analysis. Of these, nine died before day 30 and 19 died before day 180 post-admission. Admission-soluble urokinase-type plasminogen activator receptor levels were significantly higher in both day 30 and day 180 non-survivors. There was a non-significant trend towards higher macrophage migration inhibitory factor concentrations in day 30 non-survivors. Soluble triggering receptor expressed on myeloid cells-1 levels were significantly lower in non-survivors at both time points. The simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores were significantly higher in non-survivors at both time points, indicating that these models intended for use in intensive care units might also be useful in an emergency department setting.

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy.

Antiretroviral therapy (ART) in HIV‐infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART.

The Nasal Mucosa Contains a Large Spectrum of Human Papillomavirus Types from the Betapapillomavirus and Gammapapillomavirus Genera

BACKGROUND  Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples. METHODS  Nasal samples and oral samples were obtained from 312 volunteer Danish healthcare staff (240 women and 72 men), among whom the mean age was 42 years. A total of 311 oral samples and 304 nasal samples were eligible for HPV DNA analysis. HPV types were detected by use of polymerase chain reactions with modified general primers (MGP) and Forslund-Antonsson primers (FAP) and identified by Luminex (for types detected by MGP PCR) or direct sequencing or cloning before sequencing (for types detected by FAP PCR). RESULTS  HPV DNA was detected in 6% of the oral samples and 50% of the nasal samples. Seventy-five diverse HPV types or putative HPV types were identified. HPV types within the Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus genera were detected in 3%, 31%, and 23% of the nasal samples, respectively. A putative subtype of HPV76, originally isolated from a feline oral squamous cell carcinoma, was detected in 7 nasal samples. CONCLUSION  A large spectrum of HPV types from Betapapillomavirus and Gammapapillomavirus have tropism for the nasal mucosa. The implication of the relatively high prevalence of these viruses in the nasal mucosa is unknown.

Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV‐1‐infected individuals receiving combination antiretroviral therapy

To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)‐containing regimen in HIV‐1‐infected individuals already receiving combination antiretroviral therapy (ART).

Incidence and cost of anal, penile, vaginal and vulvar cancer in Denmark

BackgroundBesides being a causative agent for genital warts and cervical cancer, human papillomavirus (HPV) contributes to 40-85% of cases of anal, penile, vaginal and vulvar cancer and precancerous lesions. HPV types 16 & 18 in particular contribute to 74-93% of these cases. Overall the number of new cases of these four cancers may be relatively high implying notable health care cost to society. The aim of this study was to estimate the incidence and the health care sector costs of anal, penile, vaginal and vulvar cancer.MethodsNew anogenital cancer patients were identified from the Danish National Cancer Register using ICD-10 diagnosis codes. Resource use in the health care sector was estimated for the year prior to diagnosis, and for the first, second and third years after diagnosis. Hospital resource use was defined in terms of registered hospital contacts, using DRG (Diagnosis Related Groups) and DAGS (Danish Outpatient Groups System) charges as cost estimates for inpatient and outpatient contacts, respectively. Health care consumption by cancer patients diagnosed in 2004–2007 was compared with that by an age- and sex-matched cohort without cancer. Hospital costs attributable to four anogenital cancers were estimated using regression analysis.ResultsThe annual incidence of anal cancer in Denmark is 1.9 per 100,000 persons. The corresponding incidence rates for penile, vaginal and vulvar cancer are 1.7, 0.9 and 3.6 per 100,000 males/females, respectively. The total number of new cases of these four cancers in Denmark is about 270 per year. In comparison, the total number of new cases cervical cancer is around 390 per year. The total cost of anogenital cancer to the hospital sector was estimated to be 7.6 million Euros per year. Costs associated with anal and vulvar cancer constituted the majority of the costs.ConclusionsAnogenital cancer incurs considerable costs to the Danish hospital sector. It is expected that the current HPV vaccination program will markedly reduce this burden.

Performance of the TREAT decision support system in an environment with a low prevalence of resistant pathogens

OBJECTIVES To evaluate a decision support system (TREAT) for guidance of empirical antimicrobial therapy in an environment with a low prevalence of resistant pathogens. METHODS A retrospective trial of TREAT has been performed at Copenhagen University, Hvidovre Hospital. The cohort of patients included adults with systemic inflammation and suspicion of community-acquired bacterial infection. The empirical antimicrobial treatment recommended by TREAT was compared with the empirical antimicrobial treatment prescribed by the first attending clinical physician. RESULTS Out of 171 patients recruited, 161 (65 with microbiologically documented infections) fulfilled the inclusion criteria of TREAT. Coverage achieved by TREAT was significantly higher than that by clinical practice (86% versus 66%, P = 0.007). There was no significant difference in the cost of future resistance between treatments chosen by TREAT and those by physicians. The direct expenses for antimicrobials were higher in TREAT when including patients without antimicrobial treatment, while there was no significant difference otherwise. The cost of side effects was significantly lower using TREAT. CONCLUSIONS The results of the study suggest that TREAT can improve the appropriateness of antimicrobial therapy and reduce the cost of side effects in regions with a low prevalence of resistant pathogens, however, at the expense of increased use of antibiotics.

Effects of Anti–Tumor Necrosis Factor Therapy on Body Composition and Insulin Sensitivity in Patients With Psoriasis

Accepted for Publication: March 18, 2012. Author Affiliations: Prevention Research Center, Department of Biobehavioral Health (Drs Mallett and Turrisi and Mss Comer, Read, Varvil-Weld, Favero, and Guttman), and Department of Dermatology (Dr Billingsley), Milton S. Hershey Medical Center, The Pennsylvania State University, State College; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Ms Gaber and Dr Robinson). Correspondence: Dr Mallett, Prevention Research Center, The Pennsylvania State University, 204 E Calder Way, Ste 208, State College, PA 16801 (kmallett@psu.edu). Author Contributions: Drs Mallett and Turrisi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Mallett, Turrisi, and Billingsley. Acquisition of data: Mallett, Turrisi, Comer, Read, Varvil-Weld, Gaber, Favero, Guttman, and Robinson. Analysis and interpretation of data: Mallett, Turrisi, and Comer. Drafting of the manuscript: Mallett, Comer, Read, and Favero. Critical revision of the manuscript for important intellectual content: Mallett, Turrisi, Billingsley, Comer, Varvil-Weld, Gaber, Guttman, and Robinson. Statistical analysis: Mallett and Turrisi. Obtained funding: Mallett, and Turrisi. Administrative, technical, and material support: Comer, Read, Favero, Guttman, and Robinson. Study supervision: Turrisi. Financial Disclosure: None reported. Funding/Support: This study was supported in part by National Cancer Institute grant R03 CA144435 (Dr Mallett).

Prevalence of Human Papillomavirus in Anal and Oral Sites Among Patients with Genital Warts

Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.