Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

Rapid implementation of home oxygen treatment and remote monitoring for COVID-19 patients at the verge of the Omicron wave in Turku, Finland.

BACKGROUND: In Turku, Finland, we introduced a home oxygen treatment and app-based monitoring program for hospitalized COVID-19 patients to facilitate an early discharge during the Omicron wave. In this case series we explore the clinical parameters of patients enrolled in the program and evaluate the cost-benefit and safety issues of the program. METHODS: Hospitalized COVID-19 patients with marked hypoxemia but otherwise in stable condition were screened from Turku City Hospital and Turku University Hospital by treating doctors for eligibility in the program. Peripheral oxygen saturation of > 92% and breathing frequency < 30/min in rest with oxygen supplementation were among the criteria. All patients actively participating in the program between 10th of January 2022 and 30th of September 2022 were included in this case series. Clinical data of hospitalization and monitoring were analysed, and cost-benefit evaluation was based on the number of saved hospitalization days. RESULTS: Nineteen COVID-19 patients were included in this case series and recruited from three different hospital departments in the Turku city region, South-West Finland. All patients were male, the median age was 59 years and the median duration of hospitalization before enrolment in the program was 6 days (range 3-20 days). The median duration of home oxygen treatment was 13 days (range 3-72 days) and the median duration of home monitoring was 18 days (range 7-41 days). A total of 210,5 hospital days were prevented, resulting in savings of €144,490 of healthcare expenditure (on average 9 days and €7,605 per patient). No major safety issues were reported during the program. CONCLUSIONS: In our case series, home oxygen treatment combined with home monitoring was safe and economically beneficial. Application based monitoring could be considered in other post-acute pulmonary conditions to reduce hospitalization and healthcare costs.

Presence of Streptococcus pyogenes in the throat in invasive Group A Streptococcal disease: a prospective two-year study in two health districts, Finland.

PURPOSE: Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human pathogen that can cause severe invasive (iGAS) infections. Throat carriage has been assumed to possibly lead to hematogenous seeding. Retrospective studies may estimate the incidence of throat carriage in iGAS patients inaccurately. In this study we aimed to gather data on the presence of GAS in the throat among iGAS patients in a prospective setting. METHODS: We conducted a prospective clinical study covering iGAS infections in adult patients in two university hospitals in Finland from June 2018 to July 2020. Recruited patients' throats were swabbed for culture and isothermal amplification tests (IAT) to search for GAS. The study was registered at ClinicalTrials.gov as ID NCT03507101. RESULTS: We enrolled 45 patients. Throat swabs were obtained from 39/45 (87%) patients. Ten patients (22%) had a positive IAT for GAS. They were statistically significantly more likely to be male (9/10 [90%] vs 13/29 [45%], p = .024). Several different emm types caused the iGAS infections. CONCLUSIONS: GAS was frequently observed in throat swabs of patients with iGAS infection. This may suggest that hematogenous seeding from the nasopharynx is a possible portal of entry.

Bacterial meningitis in adults: a retrospective study among 148 patients in an 8-year period in a university hospital, Finland.

BACKGROUND: Bacterial meningitis (BM) causes significant morbidity and mortality. We investigated predisposing factors, clinical characteristics, spectrum of etiological bacteria, and clinical outcome of community-acquired and nosocomial BM. METHODS: In this retrospective study we analyzed data of 148 adults (age > 16 years) with BM treated in Turku University Hospital, Southwestern Finland, from 2011 to 2018. Besides culture- or polymerase chain reaction (PCR)-positive cases we also included culture-negative cases with laboratory parameters strongly suggestive of BM and those with meningitis-related findings in imaging. We used Glasgow Outcome Scale (GOS) score 1-4 to determine unfavorable outcome. RESULTS: The median age of patients was 57 years and 48.6% were male. Cerebrospinal fluid (CSF) culture for bacteria showed positivity in 50 (33.8%) cases, although pre-diagnostic antibiotic use was frequent (85, 57.4%). The most common pathogens in CSF culture were Streptococcus pneumoniae (11, 7.4%), Staphylococcus epidermidis (7, 4.7%), Staphylococcus aureus (6, 4.1%) and Neisseria meningitidis (6, 4.1%). Thirty-nine patients (26.4%) presented with the triad of fever, headache, and neck stiffness. A neurosurgical procedure or an acute cerebral incident prior BM was recorded in 74 patients (50%). Most of the patients had nosocomial BM (82, 55.4%) and the rest (66, 44.6%) community-acquired BM. Ceftriaxone and vancomycin were the most used antibiotics. Causative pathogens had resistances against the following antibiotics: cefuroxime with a frequency of 6.8%, ampicillin (6.1%), and tetracycline (6.1%). The case fatality rate was 8.8% and the additional likelihood of unfavorable outcome 40.5%. Headache, decreased general condition, head computed tomography (CT) and magnetic resonance imaging (MRI), hypertension, altered mental status, confusion, operative treatment, neurological symptoms, pre-diagnostic antibiotic use and oral antibiotics on discharge were associated with unfavorable outcome. CONCLUSIONS: The number of cases with nosocomial BM was surprisingly high and should be further investigated. The usage of pre-diagnostic antibiotics was also quite high. Headache was associated with unfavorable outcome. The frequency of unfavorable outcome of BM was 40.5%, although mortality in our patients was lower than in most previous studies.

Association of human myxovirus resistance protein A with severity of COVID-19.

BACKGROUND: In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients. METHODS: All 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization. RESULTS: Higher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11-46.58; p = 0.004) in patients with MxA between 400 µg/L and 799 µg/L (p = 0.004) and 20.08 (95%CI 4.51-89.44; p < 0.001) in patients with MxA ≥ 800 µg/L in comparison with patients with initial MxA < 400 µg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001). CONCLUSIONS: Higher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease.

Acute kidney injury in group A streptococcal bacteraemia: incidence, outcome and predictive value of C-reactive protein.

BACKGROUND: A ubiquitous human pathogen, Streptococcus pyogenes (Group A Streptococcus, GAS) causes infections from mild pharyngitis to severe septic infections. Acute kidney injury (AKI) is a condition of prompt decline of renal function. The aim of the present study was to report the incidence and outcome of AKI in GAS bacteraemia and to evaluate the diagnostic value of serum C-reactive protein as an indicator of AKI. METHODS: All adult patients with GAS bacteraemia treated at Turku University Hospital from 2007 to 2018 were identified and their patient records were scrutinised. RESULTS: Of 195 included patients, 38 (19.5%) had AKI stage 1, 20 (10.3%) AKI stage 2 and 26 (13.3%) AKI stage 3 and 111 (56.9%) did not have AKI. The adjusted seven-day mortality was significantly higher in AKI stages 2 and 3 compared to the non-AKI group (15% and 19% vs. 3.6%; p = .046 and .006, respectively). Of the survivors, 95.8% met the criteria of renal recovery at discharge. The higher the AKI stage, the higher was the mean serum CRP level on admission. The optimal cut-off for CRP to identify patients with AKI stage 2 or 3 was ≥244 mg/l (sensitivity 82.6% and specificity 75.8%). CONCLUSIONS: AKI is common in patients with GAS bacteraemia and the severity of AKI correlates with the CRP level on admission. The mortality of patients with GAS bacteraemia and AKI is significantly higher than of patients without AKI. Most survivors, however, show renal recovery.Key MessageAKI is common in group A Streptococcal bacteraemia and increases mortality compared to bacteraemia alone. However, renal recovery is also common. A high CRP level on admission correlates significantly positively with the degree of severity of AKI.

Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis.

We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63, 3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.

Long-Lasting T Cell Responses in BNT162b2 COVID-19 mRNA Vaccinees and COVID-19 Convalescent Patients.

The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels.

Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM-a prospective, randomized, single-centre, open-label study.

OBJECTIVES: Severe COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage. METHODS: Patients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission. RESULTS: Clinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7-12) in the TCZ group and 12 days (interquartile range, 9-15) in the control group (p = 0.014). DISCUSSION: In patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.

Low pre-vaccination SARS-CoV-2 seroprevalence in Finnish health care workers: a prospective cohort study.

BACKGROUND: Health care workers are at risk of acquiring SARS-CoV-2 infection. Our aim was to study the prevalence of SARS-CoV-2 nucleoprotein and spike protein specific antibodies in health care workers with occupational exposure to COVID-19 in Turku, Finland, from May to December 2020. METHODS: Health care workers of Turku University Hospital units caring for COVID-19 patients or handling clinical SARS-CoV-2 samples were invited to participate in the study. The presence of SARS-CoV-2 nucleoprotein and spike protein specific IgG antibodies were analysed with in-house enzyme immunoassay. RESULTS: At study enrolment, only one of the 222 (0.5%) study participants was seropositive for SARS-CoV-2 protein specific antibodies. Two additional study participants (2/222, 0.9%) seroconverted during the follow-up. All these participants were diagnosed with a RT-PCR-positive COVID-19 infection before turning seropositive. CONCLUSION: In our study population, the prevalence of SARS-CoV-2 seropositivity remained low. The absence of seropositive cases without previous RT-PCR confirmed infections demonstrate good access to diagnostics. In addition to high vaccine coverage, high standards of infection prevention practices and use of standard personal protective equipment seem sufficient in preventing occupational SARS-CoV-2 infection in a setting with low number of circulating virus. However, it remains unclear whether similar protective practices would also be effective against more transmissible SARS-CoV-2 variants.

Consumption of healthcare services and antibiotics in patients with presumed disseminated Lyme borreliosis before and after evaluation of an infectious disease specialist.

Our objective was to study the consumption of healthcare services and antibiotics in patients with suspicion of disseminated Lyme borreliosis (LB) before and after consultation of an infectious disease specialist. We evaluated retrospectively all presumed disseminated LB patients (n = 256) with a referral to the Department of Infectious Diseases (DID) in Helsinki University Hospital in 2013. Medical records from all healthcare providers in the area were reviewed and the number of physician contacts because of symptoms leading to LB suspicion and antimicrobial purchases were calculated 1 year before and after consultation or treatment at the DID. Patients were divided into three groups according to certainty of LB: unlikely, possible or probable/definite LB. The number of healthcare contacts 1 year before referral was higher among 121 patients with unlikely LB (6; interquartile range [IQR] 3-10), than 65 possible (4; IQR 2.5-7; p = 0.018) or 66 probable/definite LB patients (4; IQR 2.8-7; p = 0.010). The median number of contacts to healthcare during one year after consultation or treatment was 3 (IQR 0.5-7), 1 (IQR 0-3) and 0.5 (IQR 0-2.3), respectively, with a statistically significant difference between the groups (p<0.001). Antibiotics were purchased by 151 (60%) patients one year before referral and by 127 (50%) patients year after consultation or treatment at DID without statistically significant difference between groups with different LB certainty. These antibiotic purchases do not include the treatments prescribed by infectious disease specialists. In the case of 27 patients, an antimicrobial treatment was recommended in the consultation reply. In conclusion, patients with unlikely LB used more healthcare services than patients with possible or probable/definite LB. Antimicrobial consumption was similar between groups of different LB certainty.

Rapid detection of bacterial infection using a novel single-tube, four-colour flow cytometric method: Comparison with PCT and CRP.

BACKGROUND: A key factor behind the unnecessary use of antibiotics is the lack of rapid and accurate diagnostic tests. In this study, we developed a novel and fast flow cytometric single-tube method to detect bacterial infections within 30 minutes. METHODS: Quantitative flow cytometric four-colour analysis of host biomarkers CD35, CD64, CD329, and MHC class I expression on neutrophils and lymphocytes was performed on samples taken from 841 febrile patients with suspected infection. Obtained data was incorporated into the four-colour bacterial infection (FCBI)-index, using the developed bacterial infection algorithm. FINDINGS: In distinguishing between microbiologically confirmed bacterial (n = 193) and viral (n = 291) infections, the FCBI-index method was superior to serum C-reactive protein (CRP) and procalcitonin (PCT). In 269 confirmed viral respiratory tract infections, 43% (95% CI: 37-49%) of the patients had an increased FCBI-index, suggesting probable bacterial coinfection. INTERPRETATION: The proposed FCBI-index test might be a potent additional tool when assessing appropriateness of empiric antibiotic treatment. FUNDING: This study has been financially supported by Turku University Hospital (Turku, Finland) and The Finnish Medical Foundation.

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

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

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.

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

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.

C6 peptide enzyme immunoassay in Lyme borreliosis serology.

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.

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

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.

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

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.

18F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

BACKGROUND: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection. METHODS AND RESULTS: Thirty patients with suspected CIED infection underwent 18F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18F-FDG-PET/CT. 18F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18F-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. 18F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUVmax 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 18F-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: 18F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.