Publications by authors named "Jarmo Oksi"

38 Publications

Short- and long-term outcomes of infective endocarditis admission in adults: A population-based registry study in Finland.

PLoS One 2021 15;16(7):e0254553. Epub 2021 Jul 15.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Infective endocarditis (IE) is associated with high mortality. However, data on factors associated with length of stay (LOS) in hospital due to IE are scarce. In addition, long-term mortality of more than 1 year is inadequately known. In this large population-based study we investigated age and sex differences, temporal trends, and factors affecting the LOS in patients with IE and in-hospital, 1-year, 5-year and 10-year mortality of IE. Data on patients (≥18 years of age) admitted to hospital due to IE in Finland during 2005-2014 were collected retrospectively from nationwide obligatory registries. We included 2166 patients in our study. Of the patients 67.8% were men. Women were older than men (mean age 63.3 vs. 59.5, p<0.001). The median LOS was 20.0 days in men and 18.0 in women, p = 0.015. In the youngest patients (18-39 years) the median LOS was significantly longer than in the oldest patients (≥80 years) (24.0 vs. 16.0 days, p = 0.014). In-hospital mortality was 10% with no difference between men and women. Mortality was 22.7% at 1 year whereas 5- and 10-year mortality was 37.5% and 48.5%, respectively. The 5-year and 10-year mortality was higher in women (HR 1.18, p = 0.034; HR 1.18, p = 0.021). Both in-hospital and long-term mortality increased significantly with aging and comorbidity burden. Both mortality and LOS remained stable over the study period. In conclusion, men had longer hospital stays due to IE compared to women. The 5- and 10-year mortality was higher in women. The mortality of IE or LOS did not change over time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254553PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282023PMC
July 2021

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

JAMA 2021 08;326(6):499-518

Medanta-The Medicity, Institute of Liver Transplantation and Regenerative Medicine, Gurugram, India.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.

Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.

Data Extraction And Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.

Main Outcomes And Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.

Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).

Conclusions And Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

Trial Registration: PROSPERO Identifier: CRD42021230155.
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http://dx.doi.org/10.1001/jama.2021.11330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261689PMC
August 2021

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018.

Infect Dis (Lond) 2021 09 11;53(9):684-690. Epub 2021 May 11.

HUS Diagnostic Center, HUSLAB, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland.

Methods: We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected.

Results: A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients.

Conclusions: To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.
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http://dx.doi.org/10.1080/23744235.2021.1922753DOI Listing
September 2021

C6 peptide enzyme immunoassay in Lyme borreliosis serology.

J Microbiol Methods 2021 01 14;180:106122. Epub 2020 Dec 14.

Institute of Biomedicine, University of Turku, Turku, Finland; Laboratory Division, Clinical Microbiology, Turku University Hospital, Turku, Finland.

The cut-off values used in C6 peptide-based enzyme immunoassay (EIA), a widely used test in Lyme borreliosis (LB) serology, have not been thoroughly analysed. The objective of the study was to examine the performance of the C6 EIA, and to determine optimal cut-off values for the test. The analysed data contained results of 1368 serum samples. C6 EIA index values were compared statistically with the immunoblot (IB) test results. The identified cut-off values were further tested in a well-defined LB patient cohort. Cut-off value 1.6 appeared to be optimal when C6 EIA was used as a stand-alone test. When using C6 EIA as the first-tier test, the optimal cut-off values were 0.9 and 2.4 for negative and positive results. When C6 EIA was used as a second-tier test, samples yielding C6 index values ≥3.0 could be considered positive. The identified cut-off values had also a high sensitivity to identify seropositivity among definite LB patients. The identified cut-off values refine the role of C6 EIA in LB serology. Importantly, the use of C6 EIA leads to a reduction in the number of samples that need to be analysed using an IB, thus also reducing the costs. Two alternative workflows for LB serology including the C6 EIA are suggested.
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http://dx.doi.org/10.1016/j.mimet.2020.106122DOI Listing
January 2021

Suspicion of Lyme borreliosis in patients referred to an infectious diseases clinic: what did the patients really have?

Clin Microbiol Infect 2021 Jul 23;27(7):1022-1028. Epub 2020 Sep 23.

Division of Infectious Diseases, Inflammation Centre, Helsinki University Hospital and University of Helsinki, Finland.

Objective: To evaluate the conditions behind the symptoms in patients with suspected Lyme borreliosis (LB) who were referred to an infectious diseases clinic.

Methods: In this retrospective, population-based study, we collected data from the medical records of all patients referred for infectious disease consultations in 2013 due to presumed LB from a population of 1.58 million. The patients were classified according to the certainty of LB on the basis of their symptoms, signs and laboratory results. Data on the outcomes and subsequent alternative diagnoses during the 4-year follow-up period were reviewed from all of the available patient records from public, private and occupational healthcare providers.

Results: A total of 256 patients (16/100 000) were referred as a result of suspicion of LB; 30 (12%) of 256 were classified with definite, 36 (14%) with probable and 65 (25%) with possible LB. LB was unlikely in 121 (47%) patients. A novel diagnosis was discovered in the background symptoms in 73 (29%) of patients. Previously diagnosed comorbidities caused at least some of the symptoms in 48 (19%) patients. Other explanations for symptoms were found in 81 (67%) of 121 of unlikely and 22 (34%) of 65 of possible LB patients. The spectrum of conditions behind the symptoms was quite broad and most often were musculoskeletal, neurological, psychological or functional disorders.

Conclusions: LB was unlikely in half of the patients with presumed LB. In most cases the patients had other conditions that explained their symptoms.
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http://dx.doi.org/10.1016/j.cmi.2020.09.022DOI Listing
July 2021

F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

J Nucl Cardiol 2020 Jul 31. Epub 2020 Jul 31.

Division of Medicine, Turku University Hospital, P.O. Box 52, 20521, Turku, Finland.

Background: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection.

Methods And Results: Thirty patients with suspected CIED infection underwent F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related F-FDG-PET/CT. F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUV) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUV of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%.

Conclusions: F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.
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http://dx.doi.org/10.1007/s12350-020-02256-4DOI Listing
July 2020

Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients.

J Fungi (Basel) 2020 Mar 13;6(1). Epub 2020 Mar 13.

Department of Internal Medicine I, Bone Marrow Transplant-Unit, Medical University of Vienna, 1090 Vienna, Austria.

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases ( = 69; 49%), hematology ( = 68; 48%), and others ( = 41; 29%). BCT was performed in 57% ( = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% ( = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.
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http://dx.doi.org/10.3390/jof6010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151030PMC
March 2020

Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial.

Clin Infect Dis 2021 04;72(8):1323-1331

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Background: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB.

Methods: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months.

Results: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally.

Conclusions: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB.

Clinical Trials Registration: NCT01635530 and EudraCT 2012-000313-37.
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http://dx.doi.org/10.1093/cid/ciaa217DOI Listing
April 2021

Group A streptococcal bacteremias in Southwest Finland 2007-2018: epidemiology and role of infectious diseases consultation in antibiotic treatment selection.

Eur J Clin Microbiol Infect Dis 2020 Jul 25;39(7):1339-1348. Epub 2020 Feb 25.

Department of Infectious Diseases, Turku University Hospital, University of Turku, Turku, Finland.

The incidence of invasive group A streptococcal (GAS) infections has shown a fluctuating but increasing trend in Finland. The impact of infectious diseases specialist consultation (IDSC) on the antimicrobial therapy of GAS bacteremia has not been studied earlier. A retrospective study on adult GAS bacteremia in The Hospital District of Southwest Finland (HDSWF) was conducted from 2007 to 2018. Data on incidence of bacteremic GAS cases were gathered from the National Infectious Disease Register. Clinical data were obtained by reviewing the electronic patient records. The overall incidence of GAS bacteremia in HDSWF was 3.52/100,000, but year-to-year variation was observed with the highest incidence of 7.93/100,000 in 2018. A total of 212 adult GAS bacteremia cases were included. A record of IDSC was found (+) in 117 (55.2%) cases, not found (-) in 71 (33.5%) cases and data were not available in 24 (11.3%) cases. Among IDSC+ cases, 57.3% were on penicillin G treatment whereas in the group IDSC- only 22.5%, respectively (OR = 4.61, 95% CI 2.37-8.97; p < 0.001). The use of clindamycin as adjunctive antibiotic was more common among IDSC+ (54.7%) than IDSC- (21.7%) (OR = 4.51, 95% CI 2.29-8.87; p < 0.001). There was an increasing trend in incidence of GAS bacteremia during the study period. Narrow-spectrum beta-lactam antibiotics were chosen, and adjunctive clindamycin was more commonly used, if IDSC took place. This highlights the importance of availability of IDSC but calls for improved practice among infectious diseases specialists by avoiding combination therapy with clindamycin in non-severe invasive GAS infections.
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http://dx.doi.org/10.1007/s10096-020-03851-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303095PMC
July 2020

Treatment of infection.

Ann Med 2020 Feb - Mar;52(1-2):12-20. Epub 2019 Dec 13.

Department of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland.

(formerly: ) infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of community-acquired infections is increasing. CDI is generally associated with changes in the normal intestinal microbiota caused by administration of antibiotics. Elderly and immunocompromised patients are at greater risk for CDI and CDI recurrence. Recently, the treatment options of CDI have undergone major changes: current recommendations speak against using metronidazole for primary CDI, fidaxomicin and bezlotoxumab have been added to the treatment armamentarium and microbial replacement therapies have emerged. Several other therapies are undergoing clinical trials. In this article, we review current treatment guidelines, present the most recent data on the options to treat CDI and glance towards future developments.KEY MESSAGESThe cornerstones for the treatment of CDI are vancomycin and fidaxomicin. Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence.In recurrent CDI, bezlotoxumab infusion (a monoclonal antibody against toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence.Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI.
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http://dx.doi.org/10.1080/07853890.2019.1701703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877971PMC
December 2020

Occurrence of fatal infective endocarditis: a population-based study in Finland.

BMC Infect Dis 2019 Nov 21;19(1):987. Epub 2019 Nov 21.

Heart Center, Turku University Hospital and University of Turku, PO Box 52, 20521, Turku, Finland.

Background: Infective endocarditis (IE) is a serious mainly bacterial infection associated with high mortality. Epidemiology of fatal IE is however largely unknown. We studied occurrence and trends of fatal IE in a population-based setting.

Methods: All adults (≥18 years of age) who deceased due to IE in Finland during 2004-2016 were studied. Data was collected from the nationwide, obligatory Cause of Death Registry. Background population consisted of 28,657,870 person-years and 651,556 deaths.

Results: Infective endocarditis contributed to death in 754 cases and was the underlying cause of death in 352 cases. The standardized incidence rate of deaths associated with IE was 1.42 (95% confidence interval (CI): 1.32-1.52) per 100,000 person-years. Incidence rate increased progressively with aging from 50 years of age. Men had a two-fold risk of acquiring fatal infective endocarditis compared to women (risk ratio (RR) 1.95; 95% CI: 1.71-2.22; P < 0.0001). On average, IE contributed to 1.16 (95% CI: 1.08-1.24) out of 1000 deaths in general adult population. The proportionate amount of deaths with IE was highest in population aged < 40 years followed by gradual decrease with aging. Incidence rate and proportion of deaths caused by IE remained stable during the study period.

Conclusions: Our study describes for the first time the population-based epidemiology of fatal IE in adults. Men had a two-fold risk of acquiring fatal IE compared to women. Although occurrence of fatal IE increased with aging, the proportion of deaths to which IE contributed was highest in young adult population.
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http://dx.doi.org/10.1186/s12879-019-4620-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873758PMC
November 2019

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.

Eur J Clin Microbiol Infect Dis 2019 Oct 29;38(10):1947-1952. Epub 2019 Jul 29.

Department of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland.

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.
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http://dx.doi.org/10.1007/s10096-019-03630-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778539PMC
October 2019

Trends in occurrence and 30-day mortality of infective endocarditis in adults: population-based registry study in Finland.

BMJ Open 2019 04 20;9(4):e026811. Epub 2019 Apr 20.

Heart Center, Turku University Hospital, Turku, Finland.

Objectives: Infective endocarditis (IE) is a life-threatening disease associated with significant mortality. We studied recent temporal trends and age and sex differences in the occurrence and short-term mortality of IE.

Design: Population based retrospective cohort study.

Setting: Data of IE hospital admissions in patients aged ≥18 years in Finland during 2005-2014 and 30-day all-cause mortality data were retrospectively collected from mandatory nationwide registries from 38 hospitals.

Outcomes: Trends and age and sex differences in occurrence. Thirty-day mortality.

Results: There were 2611 cases of IE during the study period (68.2% men, mean age 60 years). Female patients were significantly older than males (62.0 vs 59.0 years, p=0.0004). Total standardised annual incidence rate of IE admission was 6.33/100 000 person-years. Men had significantly higher risk of IE compared with women (9.5 vs 3.7/100 000; incidence rate ratios [IRR] 2.49; p<0.0001) and difference was most prominent at age 40-59 years (IRR 4.49; p<0.0001). Incidence rate varied from 5.7/100 000 in 2005 to 7.1/100 000 in 2012 with estimated average 2.1% increase per year (p=0.036) and similar trends in both sexes. Significant increasing trend was observed in patients aged 18-29 years and 30-39 years (estimated annual increase 7.6% and 7.2%, p=0.002) and borderline in patients aged 40-49 years (annual increase 3.8%, p=0.08). In older population, IE incidence rate remained stable. The overall 30-day mortality after IE admission was 11.3%. Mortality was similar between sexes, increased with ageing, and remained similar during the study period.

Conclusions: Occurrence of IE is increasing in young adults in Finland. Men, especially middle-aged, are at higher risk for IE compared with women. Thirty-day mortality has remained stable at 11%, increased with ageing, and was similar between sexes.
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http://dx.doi.org/10.1136/bmjopen-2018-026811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500343PMC
April 2019

A single-tube two-color flow cytometric method for distinguishing between febrile bacterial and viral infections.

J Microbiol Methods 2018 09 29;152:61-68. Epub 2018 Jul 29.

Turku University Hospital, Department of Medicine, Turku, Finland.

The aim of this study was to develop a rapid single-tube two-color flow cytometric method to distinguish between febrile bacterial and viral infections. In this prospective comparative study, the quantitative flow cytometric analysis of CD35 and CD64 on isolated human leukocytes was obtained from 286 hospitalized febrile patients, of which 197 patients were found to have either a bacterial (n = 136) or viral (n = 61) infection. The data from infected patients was compared to 49 healthy controls and 23 patients in an inflammatory state. We developed a flow cytometric marker for bacterial infections, defined as the two-color bacterial infection index (TC-BI-index), by incorporating the quantitative analysis of CD35 and CD64 on isolated neutrophils, monocytes, and B-lymphocytes, which displayed 90% sensitivity and specificity in distinguishing between microbiologically confirmed bacterial (n = 77) and viral infections (n = 61) within 45 min. We propose that TC-BI-index test will be useful in assisting physicians to ascertain whether antibiotic treatment is required, thus limiting unnecessary antimicrobial usage.
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http://dx.doi.org/10.1016/j.mimet.2018.07.015DOI Listing
September 2018

Capnocytophaga canimorsus: a rare case of conservatively treated prosthetic valve endocarditis.

APMIS 2018 May;126(5):453-456

Division of Medicine, Turku University Hospital, Turku, Finland.

We describe a rare case of prosthetic valve endocarditis caused by the canine bacterium Capnocytophaga canimorsus in a male aged 73 years. The diagnosis of infective endocarditis was unequivocal, as it blood cultures were positive for C. canimorsus and vegetations were detected on transesophageal echocardiography; the modified Duke criteria were fulfilled. PET-CT showed intense F-FDG uptake of the prosthetic valve area. The patient was treated with antibiotics alone (no surgery), and is now on life-long suppressive antibiotic therapy. To our knowledge, this is the third reported case of prosthetic valve endocarditis caused by C. canimorsus and the first one to have been treated conservatively.
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http://dx.doi.org/10.1111/apm.12839DOI Listing
May 2018

Point-of-care testing for CXCL13 in Lyme neuroborreliosis.

Diagn Microbiol Infect Dis 2018 Jul 23;91(3):226-228. Epub 2018 Feb 23.

Institute of Biomedicine, University of Turku, Turku, Finland; Microbiology and Genetics Department, Turku University Hospital, Turku, Finland. Electronic address:

Cerebrospinal fluid chemokine (C-X-C motif) ligand 13 (CXCL13) is a marker for Lyme neuroborreliosis (LNB). CXCL13 lateral flow immunoassay (LFA) was compared with CXCL13 ELISA. CXCL13 LFA results correlated strongly with CXCL13 ELISA results. CXCL13 LFA is a rapid and easy-to-perform test, which is suitable for routine point-of-care diagnostics of suspected LNB patients.
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http://dx.doi.org/10.1016/j.diagmicrobio.2018.02.013DOI Listing
July 2018

Head-to-Head Comparison of Ga-Citrate and F-FDG PET/CT for Detection of Infectious Foci in Patients with Bacteraemia.

Contrast Media Mol Imaging 2017 17;2017:3179607. Epub 2017 Oct 17.

Turku PET Centre, University of Turku, Turku, Finland.

Purpose: This study evaluated the potential of Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with bacteraemia by comparing it with 2-[F]fluoro-2-deoxy--glucose (F-FDG) PET/CT.

Methods: Four patients admitted to hospital due to bacteraemia underwent both F-FDG and Ga-citrate whole-body PET/CT scans to detect infectious foci.

Results: The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4-10 days. The time interval between F-FDG and Ga-citrate PET/CT was 1-4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both F-FDG (maximum standardised uptake value [SUV] 6.0 ± 1.0) and Ga-citrate (SUV  6.8 ± 3.5, = 0.61). Three patients had soft tissue infectious foci, with more intense F-FDG uptake (SUV  6.5 ± 2.5) than Ga-citrate uptake (SUV  3.9 ± 1.2, = 0.0033).

Conclusions: Our small cohort of patients with bacteraemia revealed that Ga-citrate PET/CT is comparable to F-FDG PET/CT for detection of osteomyelitis, whereas F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.
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http://dx.doi.org/10.1155/2017/3179607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664237PMC
July 2018

Cerebral vasculitis and intracranial multiple aneurysms in a child with Lyme neuroborreliosis.

JMM Case Rep 2017 Apr 21;4(4):e005090. Epub 2017 Apr 21.

Department of Infectious Diseases, Division of Medicine, Faculty of Medicine, University of Turku, Turku University Hospital, P.O. Box 52, 20521 Turku, Finland.

Lyme borreliosis is a multisystem tick-borne disease caused by . Neurological manifestations are reported in up to 15 % of adult patients with Lyme disease, while the frequency among children is higher. The most common manifestations are painful radiculopathy, facial nerve paresis and lymphocytic meningitis. Epileptic seizures and cerebral vasculitis with stroke or aneurysms are very rare complications. We describe a paediatric patient with sensorineural auditory dysfunction, headache, fatigue and epileptic seizures as sequelae of meningoencephalitis/Lyme neuroborreliosis (LNB) caused by . Brain magnetic resonance imaging revealed widespread enhancement of the leptomeninges, cranial nerves and artery walls compatible with vasculitis and disturbances in cerebrospinal fluid (CSF) circulation. The patient was treated with ceftriaxone for 2 weeks. Two years later, the patient had an ischemic stroke. Brain magnetic resonance angiography revealed multiple aneurysms, which were not present previously. The largest aneurysm was operated rapidly. The patient was treated with another course of intravenous ceftriaxone for 4 weeks and pulse therapy with corticosteroids. He recovered well.

Conclusion: . This unique case demonstrates complications of LNB that can result in serious morbidity or even mortality. Lumbar puncture and analysis should be considered for paediatric patients with epileptic seizures or cerebrovascular events living in a Lyme borreliosis endemic area.
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http://dx.doi.org/10.1099/jmmcr.0.005090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630958PMC
April 2017

Louse-borne relapsing fever in Finland in two asylum seekers from Somalia.

APMIS 2017 Jan 16;125(1):59-62. Epub 2016 Nov 16.

University of Turku and Turku University Hospital, Turku, Finland.

We report two cases of louse-borne relapsing fever (LBRF) in young Somali asylum seekers having recently arrived to Finland. They had sought medical attention for a febrile illness. Blood smears were examined for suspected malaria, but instead, spirochete shaped bacteria were observed. The bacteria were confirmed as Borrelia recurrentis by PCR and sequencing. The patients survived, but their treatment was complicated by Jarisch-Herxheimer reaction. We conclude that LBRF must be considered as a diagnostic option in febrile refugees also in the northernmost parts of Europe.
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http://dx.doi.org/10.1111/apm.12635DOI Listing
January 2017

Scedosporium apiospermum as a rare cause of central skull base osteomyelitis.

Med Mycol Case Rep 2016 Mar 7;11:28-30. Epub 2016 Apr 7.

Department of Infectious Diseases, Division of Medicine, Turku University Hospital, Turku, Finland; Faculty of Medicine, Turku University, Turku, Finland.

We report a case of Scedosporium apiospermum mold causing ear infection, central skull base osteomyelitis and finally, occlusion of carotid artery in a 48-year-old diabetic man. The exact diagnosis was established and the severity of the disease understood several months after the onset of symptoms. Despite of appropriate antifungal therapy, and repeated surgical and otological procedures, the infection progressed to fatal cerebral infarction.
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http://dx.doi.org/10.1016/j.mmcr.2016.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834721PMC
March 2016

Clinical picture and overall status of newly diagnosed HIV patients at Turku University Hospital in 2013.

Duodecim 2016;132(21):2001-8

Our patient material consists of the 12 patients diagnosed during one year. In all cases, sex was the likely mode of transmission, the number of partners having been high for some patients. Some of the cases were originally detected as a result of contact tracing. In two patients the disease had already at the time of diagnosis progressed to the AIDS stage, naturally complicating the initial phase of treatment. In a quarter of our patients the disease could have been discovered earlier from the symptoms of the primary infection, provided that testing had been done. Adherence to treatment in a HIV patient and treatment outcome are usually excellent.
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January 2018

Relapsing fever.

Duodecim 2016;132(21):1952-6

Relapsing fewer is an infection to be considered in the differential diagnosis of an immigrant´s febrile illness. It is a severe, tick-borne or body louse-borne infection caused by the relapsing fever associated borrelia species. The body louse-borne infection is in particular encountered in the Horn of Africa region due to poor hygiene, and has during the past year been described in several European countries as imported by refugees coming from this region. Doctors should thus bear relapsing fever in mind as a differential diagnosis in a febrile refugee having recently arrived in Finland.
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January 2018

F-FDG positron emission tomography/computed tomography in infective endocarditis.

J Nucl Cardiol 2017 02 9;24(1):195-206. Epub 2015 Dec 9.

Division of Medicine, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland.

Background: The diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in IE.

Methods: Sixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of F-FDG-PET/CT. F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUV) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference.

Results: There was strong, focal F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUV of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE.

Conclusions: F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.
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http://dx.doi.org/10.1007/s12350-015-0325-yDOI Listing
February 2017

[Tick-borne encephalitis in Finland from 2010 to 2012].

Duodecim 2015 ;131(15):1367-75

The frequency of occurrence of tick-borne encephalitis has increased significantly in Europe and Finland during the past twenty years. There has been a suspicion that the Finnish cases have at least over the last few years been more severe than described in the literature. We analyzed the approximately one hundred cases of tick-borne encephalitis diagnosed in Finland over a three-year period. In two thirds of the patients general physical condition deteriorated clearly, the disease caused permanent disability or the patients required supportive measures in the hospital, such as ventilator therapy. Assessment of the course and severity of the disease would seem to be impossible on the basis of individual symptoms, such as duration of fever.
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November 2015

[Cerebral nocardiosis as surprising cause of a convulsive seizure].

Duodecim 2014 ;130(15):1531-5

Underlying a convulsive seizure of an adult patient many different types of cause can be detected, such as alcohol withdrawal, disturbance of the cerebral circulation, cerebral hemorrhage, brain tumor, metabolic disturbances, drugs or infection. In connection with severe central nervous system infections, such as brain abscesses, convulsive seizures occur in approximately one out of five patients. A patient with brain abscess may be nonfebrile and have normal values of inflammatory markers. The diagnosis is based on contrast-enhanced CT scanning or magnetic resonance imaging of the brain. Even surgical sampling is often necessary. In our patient, a rare nocardia-induced brain abscess turned out to be the cause of recurrent convulsive seizures.
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November 2014

CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation.

J Neuroinflammation 2014 Jun 11;11:103. Epub 2014 Jun 11.

Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.

Background: Laboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi-specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases.

Methods: CXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples.

Results: The CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment.CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations decreased statistically significantly with the treatment.

Conclusions: These results clearly indicate that highly elevated CSF CXCL13 levels are strongly associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an excellent biomarker in differentiating LNB from viral CNS infections and from other neuroinflammatory conditions.
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http://dx.doi.org/10.1186/1742-2094-11-103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070086PMC
June 2014

Candida dubliniensis spondylodiscitis in an immunocompetent patient. Case report and review of the literature.

Med Mycol Case Rep 2014 Jan 13;3:4-7. Epub 2013 Nov 13.

Clinical Microbiology Laboratory, Turku University Hospital, Turku, Finland.

We describe what appears to be the first case of spondylodiscitis due to Candida dubliniensis. Our case adds to the current literature of the importance of C. dubliniensis as a cause of fungemia and subsequent deep seated infections. It highlights the importance of taking fungal as well as bacterial culture from biopsy specimens in patients with spondylodiscitis. We also review the literature covering the reported cases of Candida spondylodiscitis, which amount to about 100 over the last 5 decades.
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http://dx.doi.org/10.1016/j.mmcr.2013.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930959PMC
January 2014

Cat scratch disease caused by Bartonella grahamii in an immunocompromised patient.

J Clin Microbiol 2013 Aug 5;51(8):2781-4. Epub 2013 Jun 5.

Department of Infectious Diseases, Division of Medicine, Turku University Hospital and Faculty of Medicine, University of Turku, Turku, Finland.

Bartonella grahamii colonizes rodents worldwide and has been detected in questing Ixodes ricinus ticks. Here, the first human B. grahamii infection confirmed by multilocus sequence typing is reported. The route of transmission and clinical picture of the patient are similar to those seen in patients with cat scratch disease, which is typically diagnosed as a Bartonella henselae infection.
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http://dx.doi.org/10.1128/JCM.00910-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719609PMC
August 2013

[Central nervous system infection--tick-borne encephalitis, neuroborreliosis or both?].

Duodecim 2011 ;127(1):75-9

TYKS:n sisätautien klinikka, Turku.

Certain tick species are able to transmit both tick-borne encephalitis (TBE) and Lyme borreliosis. Therefore, it is possible that a patient can simultaneously be infected with the TBE-virus and Borrelia burgdorferi-spirochete as a result of a single tick bite. Although this is a rare event, its possibility has to be taken into account e.g. in the diagnostics of febrile patients who suffer from symptoms typical of meningoencephalitis and who live or come from endemic tick regions. This is because the treatments of these two infectious diseases differ from each other--there is a specific treatment only for Lyme borreliosis. We describe two Finnish patients with double infection with TBE and neuroborreliosis.
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April 2011

Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment.

APMIS 2010 Sep;118(9):665-73

Department of Medical Microbiology and Immunology, University of Turku, Finland.

We have earlier shown that Borrelia burgdorferi-infected and ceftriaxone-treated mice have viable spirochetes in their body, since immunosuppressive treatment allows B. burgdorferi to be detected by culture. However, the niche of the persisting spirochetes remained unknown. In the present study, we analyzed the tissues of B. burgdorferi-infected and ceftriaxone-treated mice by culture and PCR to reveal the foci of persisting spirochetes. C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks, or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment. All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30-100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.
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http://dx.doi.org/10.1111/j.1600-0463.2010.02615.xDOI Listing
September 2010
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