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.

Glioma grade and post-neurosurgical meningitis risk.

BACKGROUND: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. METHODS: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). RESULTS: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. CONCLUSIONS: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.

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.

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.

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.

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.

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.

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.

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

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.

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

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

18F-FDG positron emission tomography/computed tomography in infective endocarditis.

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-[18F]fluoro-2-deoxy-D-glucose (18F-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 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference. RESULTS: There was strong, focal 18F-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, SUVmax 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 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE. CONCLUSIONS: 18F-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.

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

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.

Relapsing fever.

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.

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

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.

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

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.

[Cerebral nocardiosis as surprising cause of a convulsive seizure]. / Aivonokardioosi kouristuskohtauksen yllättävänä aiheuttajana.

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.

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

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.

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.

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.