Comparative epidemiology of bacteraemia in two ageing populations: Singapore and Denmark.

Burden of bacteraemia is rising due to increased average life expectancy in developed countries. This study aimed to compare the epidemiology and outcomes of bacteraemia in two similarly ageing populations with different ethnicities in Singapore and Denmark. Historical cohorts from the second largest acute-care hospital in Singapore and in the hospitals of two Danish regions included patients aged 15 and above who were admitted from 1 January 2006 to 31 December 2016 with at least 1 day of hospital stay and a pathogenic organism identified. Among 13 144 and 39 073 bacteraemia patients from Singapore and Denmark, similar 30-day mortality rates (16.5%; 20.3%), length of hospital stay (median 14 (IQR: 9-28) days; 11 (6-21)), and admission rate to ICU (15.5%; 15.6%) were observed, respectively. Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus ranked among the top four in both countries. However, Singaporeans had a higher proportion of patients with diabetes (46.8%) and renal disease (29.5%) than the Danes (28.0% and 13.7%, respectively), whilst the Danes had a higher proportion of patients with chronic pulmonary disease (18.0%) and malignancy (35.3%) than Singaporeans (9.7% and 16.2%, respectively). Our study showed that top four causative organisms and clinical outcomes were similar between the two cohorts despite pre-existing comorbidities differed.

Mortality and exacerbations associated with Stenotrophomonas maltophilia in chronic obstructive pulmonary disease. A regional cohort study of 22,689 outpatients.

OBJECTIVES: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD. METHODS: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression. RESULTS: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1). CONCLUSIONS: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Bacteremia With Anaerobic Bacteria and Association With Colorectal Cancer: A Population-based Cohort Study.

BACKGROUND: There is a well-described association between bacteremia with bovis group streptococci or Clostridium septicum and an increased probability of a colorectal cancer (CRC) diagnosis. We wanted to investigate the existence of a similar association between CRC and bacteremia with other bacteria belonging to the gut microbiota.. METHODS: A population based cohort study in a population about 2 million people including 45 774 bacteremia episodes and 231 387 blood culture negative cases was performed in the Region of Southern Denmark and Region Zealand from 2007-2016. Episodes of bacteremia were combined with the Danish central register for CRC. We performed Cox's regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The study results confirmed previous findings of an increased risk of a CRC diagnosis after bacteremia with the bovis group streptococci (risk within a year: 4.3%; HR [95% CI]: 8.46 [3.51-20.4]) or C. septicum (20.8%; 76.2 [42.0-138]). Furthermore, Bacteroides ovatus (6.7%; 20.3 [5.04-81.8]), Bacteroides uniformis (5.4%; 16.2 [4.02-65.7]), Clostridium tertium (3.6 %; 13.9 [1.96-99.4]), Fusobacterium spp. (excluding F. necrophorum) (3.0 %; 8.51 [2.73-26.5]), and Gram-positive anaerobic cocci (3.6 %; 10.9 [4.50-26.3]) were also associated with an increased risk of a CRC diagnosis compared to patients with negative blood cultures (0.4%). CONCLUSIONS: Bacteremia with specific gut microbiota anaerobic bacteria is associated with a high risk of a diagnosis of CRC, indicating the need for colorectal workup. Importantly, this strategy also holds the possible additional benefit of detecting adenomas or other premalignant conditions, which were not included in the present study.

Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD. METHODS: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses. RESULTS: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001). CONCLUSION: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population.

BACKGROUND: Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown. METHODS: We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes. RESULTS: Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort. CONCLUSIONS: Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Long-Term Survival, Health, Social Functioning, and Education in Patients With an Enterovirus Central Nervous System Infection, Denmark, 1997-2016.

BACKGROUND: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood. METHODS: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency. RESULTS: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency. CONCLUSIONS: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning.

Risk of Neurological Disorders in Patients With European Lyme Neuroborreliosis: A Nationwide, Population-Based Cohort Study.

BACKGROUND: Lyme neuroborreliosis (LNB), caused by the tick-borne spirochetes of the Borrelia burgdorferi sensu lato species complex, has been suggested to be associated with a range of neurological disorders. In a nationwide, population-based cohort study, we examined the associations between LNB and dementia, Alzheimer's disease, Parkinson's disease, motor neuron disease, epilepsy, and Guillain-Barré syndrome. METHODS: We used national registers to identify all Danish residents diagnosed during 1986-2016 with LNB (n = 2067), created a gender- and age-matched comparison cohort from the general population (n = 20 670), and calculated risk estimates and hazard ratios. RESULTS: We observed no long-term increased risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, or epilepsy. However, within the first year, 8 (0.4%) of the LNB patients developed epilepsy, compared with 20 (0.1%) of the comparison cohort (difference, 0.3%; 95% confidence interval, .02-.6%). In the LNB group, 11 (0.5%) patients were diagnosed with Guillain-Barré syndrome within the first year after LNB diagnosis, compared with 0 (0.0%) in the comparison cohort. After the first year, the risk of Guillain-Barré was not increased. CONCLUSIONS: LNB patients did not have increased long-term risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, epilepsy, or Guillain-Barré. Although the absolute risk is low, LNB patients might have an increased short-term risk of epilepsy and Guillain-Barré syndrome.

Longitudinal trajectory patterns of plasma albumin and C-reactive protein levels around diagnosis, relapse, bacteraemia, and death of acute myeloid leukaemia patients.

BACKGROUND: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML). METHODS: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days). RESULTS: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event. CONCLUSIONS: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.

Rejection of the name Borreliella and all proposed species comb. nov. placed therein.

Rejection (nomen rejiciendum) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes).

Community-acquired meningitis caused by beta-haemolytic streptococci in adults: a nationwide population-based cohort study.

The objective of this study was to examine the clinical presentation of community-acquired beta-haemolytic streptococcal (BHS) meningitis in adults. This is a nationwide population-based cohort study of adults (≥ 16 years) with BHS meningitis verified by culture or polymerase chain reaction of the cerebrospinal fluid (CSF) from 1993 to 2005. We retrospectively evaluated clinical and laboratory features and assessed outcome by Glasgow Outcome Scale (GOS). We identified 54 adults (58% female) with a median age of 65 years (IQR 55-73). Mean incidence rate was 0.7 cases per 1,000,000 person-years. Alcohol abuse was noted among 11 (20%) patients. Group A streptococci (GAS) were found in 17 (32%) patients, group B (GBS) in 18 (34%), group C (GCS) in four (8%) and group G (GGS) in 14 (26%). Patients with GAS meningitis often had concomitant otitis media (47%) and mastoiditis (30%). Among patients with GBS, GCS or GGS meningitis, the most frequent concomitant focal infections were bone and soft tissue infections (19%) and endocarditis (16%). In-hospital mortality was 31% (95% CI 19-45), and 63% (95% CI 49-76) had an unfavourable outcome at discharge (GOS < 5). BHS meningitis in adults is primarily observed among the elderly and has a poor prognosis. GAS meningitis is primarily associated with concomitant ear-nose-throat infection.

Serological diagnostics of Lyme borreliosis: comparison of assays in twelve clinical laboratories in Northern Europe.

Lyme borreliosis (LB), caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, is the most common tick-borne infection in Europe. Laboratory diagnosis of LB is mainly based on the patients' medical history, clinical signs and symptoms in combination with detection of Borrelia-specific antibodies where indirect enzyme-linked-immunosorbent assay (ELISA) is the most widely used technique. The objective of the study was to evaluate and compare the diagnostic accuracy (sensitivities and specificities) of serological tests that are currently in use for diagnosis of LB in clinical laboratories in Northern Europe, by use of a large serum panel. The panel consisted of 195 serum samples from well-characterized and classified patients under investigation for clinically suspected LB (n = 59) including patients with Lyme neuroborreliosis, Lyme arthritis, acrodermatitis chronica atrophicans, erythema migrans or other diseases (n = 112). A total of 201 serum samples from healthy blood donors were also included. The panel (396 serum samples altogether) was sent to 12 clinical laboratories (using five different ELISA methods) as blinded for group affiliation and the laboratories were asked to perform serological analysis according to their routine procedure. The results from the study demonstrated high diagnostic concordance between the laboratories using the same diagnostic assay and lower diagnostic concordance between laboratories using different diagnostic assays. For IgG, the results were in general rather homogenous and showed an average sensitivity of 88% (range 85-91%) compared to IgM which showed lower average sensitivity of 59% (range 50-67%) and more heterogeneous results between assays and laboratories.

The value of seroprevalence data as surveillance tool for Lyme borreliosis in the general population: the experience of Belgium.

BACKGROUND: Serological surveillance, based on the measurement of the presence of specific antibodies in a given population, can be used in addition to traditional and routine disease surveillance methods. The added value of this has been largely documented for vaccine-preventable diseases, but to a lesser extent for vector-borne diseases. This study aimed to evaluate the utility of seroprevalence data as additional source of information on the epidemiology of Lyme borreliosis in Belgium. METHODS: In total, 3215 residual blood samples collected in 2013-2015 were analysed with Liaison® Borrelia IgG kit (DiaSorin S.p.A, Saluggia, Italy). Positive and equivocal results were further examined with immunoblotting (recomLine Borrelia IgG kit, Mikrogen, Neuried, Germany). Crude prevalence estimates of equivocal and seropositive results were calculated and further adjusted accounting for clustered sampling and standardized for age, sex and population per province, according to the Belgian population structure in 2014. The effect of age, sex and region on seropositivity was assessed using log-binomial regression. RESULTS: The overall weighted national seroprevalence for Borrelia burgdorferi sensu lato, adjusted for clustered sampling, age, sex and province was 1.06% (95%CI 0.67-1.67). Although not statistically significant, the highest prevalences were observed in men and in those younger than 15 years or older than 59 years of age. At provincial level, the seroprevalence estimates do not follow the geographical distribution of tick bites and diagnoses of Lyme borreliosis as detected through other surveillance systems. CONCLUSIONS: Although the use of residual samples for seroprevalence estimates has several advantages, it seems to be a limited tool for serological surveillance of Lyme borreliosis in Belgium, other than follow-up of trends if repeated over time. A population-based sampling strategy might provide a more representative nationwide sample, but would be very time intensive and expensive. Seroprevalence studies within risk groups or risk areas in Belgium could provide a useful alternative approach to complement routine surveillance data of Lyme borreliosis.

Prognostic accuracy of qSOFA in predicting 28-day mortality among infected patients in an emergency department: a prospective validation study.

BACKGROUND: Few prospective studies have evaluated the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) criteria in emergency department (ED)settings. The aim of this study was to determine the prognostic accuracy of qSOFA compared with systemic inflammatory response syndrome (SIRS) in predicting the 28-day mortality of infected patients admitted to an ED. METHODS: A prospective observational cohort study of all adult (≥18 years) infected patients admitted to the ED of Slagelse Hospital, Denmark, was conducted from 1 October 2017 to 31 March 2018. Patients were enrolled consecutively and data related to SIRS and qSOFA criteria were obtained from electronic triage record. Information regarding mortality was obtained from the Danish Civil Registration System. The original cut-off values of ≥2 was used to determine the prognostic accuracy of SIRS and qSOFA criteria for predicting 28-day mortality and was assessed by analyses of sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios and area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: A total of 2112 patients were included in this study. A total of 175 (8.3%) patients met at least two qSOFA criteria, while 1012 (47.9%) met at least two SIRS criteria on admission. A qSOFA criteria of at least two for predicting 28-day mortality had a sensitivity of 19.5% (95% CI 13.6% to 26.5%) and a specificity of 92.6% (95% CI 91.4% to 93.7%). A SIRS criteria of at least two for predicting 28-day mortality had a sensitivity of 52.8% (95% CI 44.8% to 60.8%) and a specificity of 52.5% (95% CI 50.2% to 54.7%). The AUROC values for qSOFA and SIRS were 0.63 (95% CI 0.59 to 0.67) and 0.52 (95% CI 0.48 to 0.57), respectively. CONCLUSION: Both SIRS and qSOFA had poor sensitivity for 28-day mortality. qSOFA improved the specificity at the expense of the sensitivity resulting in slightly higher prognostic accuracy overall.

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS. METHODS: Using a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic regression (adjusted for age and sex). RESULTS: Nine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and - 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18-137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96-1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48-4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31-2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44-0.72, p = 0.0002) were associated with reduced risk of AS. CONCLUSION: We replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.

Evidence of rickettsiae in Danish patients tested for Lyme neuroborreliosis: a retrospective study of archival samples.

BACKGROUND: With a prevalence of 4.7-13% in Danish Ixodes ricinus ticks, Rickettsia helvetica is one of the most frequently detected tick-borne organisms in Denmark. Most reports of human exposure have described asymptomatic seroconversion or a mild, self-limiting flu-like illness but it has also been implicated as a cause of subacute lymphocytic meningitis. Because Borrelia burgdorferi sensu lato (Bbsl) and R. helvetica are both found in the same tick species, potential co-transmission is a possibility. We examined 1) the seroprevalence of anti-rickettsia antibodies in patients investigated for Lyme neuroborreliosis (LNB), and 2) the cerebrospinal fluid (CSF) and sera of same patients for the presence of Rickettsia DNA. METHODS: Ninety-nine sera and 87 CSF samples from patients with intrathecal synthesis of anti-Borrelia antibodies and 101 sera and 103 CSF samples from patients with no detectable intrathecal synthesis were retrospectively examined for this study. Sera were analyzed for antibodies against spotted fever group (SFG) rickettsiae and both the CSF and sera were tested for Rickettsia DNA using a genus-specific real-time PCR. RESULTS: Of the patients tested for LNB, 32% (64/200) had IgG antibodies against SFG rickettsiae. Among patients with confirmed intrathecal synthesis of Borrelia-specific antibodies, 38% (38/99) exhibited IgG antibodies. None of these values were statistically significant when compared with sera from healthy blood donors (p = 0.7 and 0.19). Rickettsia DNA was found in the CSF of 4% (8/190) of patients. CONCLUSION: No statistically significant difference was found in the seroprevalence of anti-rickettsia antibodies in patients tested for LNB and healthy blood donors, indicative of a low rate of exposure in this group of patients. Eight patients showed evidence of Rickettsia DNA in the CSF, five of whom had LNB. However, cycle threshold (Ct) values were high, indicating low concentrations of DNA, and no apparent alteration in the clinical manifestations of LNB were noted in the medical records of these patients.

Pleural infection: a retrospective study of clinical outcome and the correlation to known etiology, co-morbidity and treatment factors.

BACKGROUND: We explored the hypothesized importance of early knowledge of microbiological etiology in patients with pleural infection, including comorbidity and treatment factors in the outcome analyses. METHODS: Data from the medical records of a large cohort of 437 consecutive patients in 9 hospitals in East-Denmark were included retrospectively. RESULTS: Microbiology, co-morbidity, therapy and outcome are described in detail. Patient groups with microbiology negative and known bacterial etiology had a similar 30-day and 90-day mortality. There were no differences in initial antibiotic treatment regimens, antibiotic treatment duration, rate of intra-pleural fibrinolysis treatment, surgical referral rate, and ICU admittance rate. Patients with microbiology negative etiology were younger (60.8 vs 64.3 years) and fewer had predisposing risk factors (59% vs 71%), but pleural drainage was more often delayed (49% vs 36%). Mortality was similar in patients treated with either of the two nationally recommended initial antibiotic regimens. However, higher 90-day mortality (22.5% vs 9.7%), disease severity (31.5% vs 6.2%), and ICU admittance rate (21.3% vs 2.9%) was observed in a sub-group with initial broad-spectrum treatment compared to patients receiving the nationally recommended initial treatments, irrespective of knowledge of etiology. Several factors correlated independently to 90-day mortality, including age, predisposing risk factors, surgical referral (Odds-Ratios > 1), drainage delay and intra-pleural fibrinolysis (ORs < 1). CONCLUSIONS: No difference was found between patients with microbiology negative and known bacterial etiology regarding outcome or treatment parameters. Treatment factors and predisposing factors independently relating to mortality were found in the cohort. Broad-spectrum antibiotics were initially used for treatment of patients with more severe illness and poorer outcome.

Influence of TVT properties on outcomes of midurethral sling procedures: high-stiffness versus low-stiffness tape.

INTRODUCTION AND HYPOTHESIS: Although there is clear consensus on the use of monofilament polypropylene tapes for treating stress urinary incontinence (SUI), tapes differ in weight, stiffness, and elasticity. In this study, we compared outcomes of two tape types: high-stiffness Intramesh SOFT L.I.F.T versus low-stiffness Intramesh L.I.F.T. tape. Our null hypothesis was that in terms of performance, SOFT tape equaled L.I.F.T. tape. METHODS: Six hundred and sixty women underwent prospective transvaginal tape (TVT) surgery for SUI: 210 had the SOFT tape placed and 450 the L.I.F.T. tape. Follow-ups were scheduled at 3 and 12 months. RESULTS: Objective cure at 3-months' follow-up was 87 % in the SOFT group vs 94 % in the L.I.F.T. group (p = 0.003) and at 12 months 86 vs 96 % (p = 0.0004), respectively. Subjective outcomes were equal. For SOFT tape, the objective failure rate at 3 months was especially pronounced in women older than 70 years: 31 vs 10 % (p = 0.008), and subjective failure was 24 vs 7 % (p = 0.01). At 12 months, objective failure for the SOFT tape was significantly higher in both age groups compared with L.I.F.T. [odds ratio (OR) 2.17]. Multivariate analysis showed that body mass index (BMI) ≥30 (OR 2.41), mixed incontinence (MUI) (OR 2.24), use of SOFT tape (OR 2.17), and age ≥ 70 years are significant independent risk factors for surgical failure. CONCLUSIONS: Outcomes with SOFT tape are significantly inferior than with L.I.F.T. tape, especially among elderly women. Therefore, the two variants of monofilament polypropylene tape are not interchangeable.