SignalP: The Evolution of a Web Server.

SignalP ( https://services.healthtech.dtu.dk/services/SignalP-6.0/ ) is a very popular prediction method for signal peptides, the intrinsic signals that make proteins secretory. The SignalP web server has existed since 1995 and is now in its sixth major version. In this historical account, we (three authors who have taken part in the entire journey plus the first author of the latest version) describe the differences between the versions and discuss the various decisions taken along the way.

COVID-19 vaccination and involuntary movements: A longitudinal panel study.

OBJECTIVE: Despite high COVID-19 vaccination rates in many populations, concerns persist about potential adverse events, including concerns about involuntary movements. While case studies have shown occurrences of involuntary movements following COVID-19 vaccination, no systematic studies have explored this association. Our study aims to investigate the relationship between COVID-19 vaccination and involuntary movements. METHODS: This study employs a longitudinal panel design. The study population consists of 165,834 responses from a total of 97,537 unique individuals sourced from the BiCoVac cohort, which is a randomly sampled cohort of Danish individuals aged 16 to 65. Data were collected through a combination of questionnaires and national registers, and analyses were conducted using mixed effects logistic regression. RESULTS: Vaccinated individuals had lower odds of reporting involuntary movements compared to non-vaccinated individuals. Although adjustments attenuated the results, a consistent pattern of lower odds was observed among the vaccinated individuals. The strongest association for the first dose was observed in individuals who received the vaccine within the last 4 weeks before reporting symptoms (OR = 0.72 (0.60; 0.85)). For the second dose, the strongest association was found in individuals who received the second vaccine dose more than 4 weeks before reporting symptoms (OR = 0.77 (0.65; 0.91)). CONCLUSION: The results of the study do not indicate involuntary movements as an adverse reaction to the COVID-19 vaccine. These findings support the safety profile of the COVID-19 vaccine concerning involuntary movements and contribute to enhancing public trust in vaccination programs.

"I think we should wait and see": A qualitative study of call-takers' decision-making in consultations with patients suffering unrecognized myocardial infarction.

OBJECTIVES: Call-takers face a complex situation when assessing medical problems in emergency medical services calls. Patients with myocardial infarction experiencing atypical symptoms risk misinterpretation. We examined development in call-takers' decision-making process in telephone consultations with patients having imminent myocardial infarction. METHODS: Recording of 38 calls among 19 patients (two per patient) who contacted Copenhagen Emergency Medical Services (Denmark) at least twice within one week before myocardial infarction diagnosis. The penultimate and last call were compared using qualitative content analysis. RESULTS: Call-takers' assessment of the condition changed from unclear symptom picture and dismissal of heart disease in penultimate call to severe condition, not heart-related, and possible heart disease in last call. Call-takers recommended watchful waiting in the penultimate call. Both calls involved response negotiation, while caution regarding misinterpretation was only seen in the penultimate call. CONCLUSION: Call-takers used different decision-making approaches when the caller's symptom descriptions appeared unclear and not corresponding with the medical understanding of severe conditions. Call-takers did not negotiate the condition's assessment but engaged in discussions about the response choice. PRACTICE IMPLICATIONS: A protocol to negotiate response choice with callers having unclear clinical conditions should be developed. Clarifying watchful waiting as a recommendation may assist call-takers' decision-making.

Diagnostic accuracy of dipsticks for urinary tract infections in acutely hospitalised patients: a prospective population-based observational cohort study.

OBJECTIVE: To determine the added diagnostic value of dipsticks for urinary tract infections (UTI) in acutely hospitalised individuals. DESIGN: Prospective population-based cohort study. SETTING: North Denmark. PARTICIPANTS: All adults (≥18 years) examined with dipsticks at emergency departments in North Denmark Region from September 20 through 23 October 2021. MAIN OUTCOME MEASURES: UTI was defined as ≥1 symptom of new-onset frequency, dysuria or suprapubic tenderness combined with a positive urine culture. Positive dipsticks were defined as any reaction for leucocyte esterase and/or nitrite. RESULTS: Dipsticks were used in 1052/2495 (42%) of acutely hospitalised patients with a median age of 73 years (IQR 57-82) and 540 (51%) were female. Overall, 89/1052 (8%) fulfilled the UTI criteria and urine cultures were done in 607/1052 (58%) patients. Among patients examined with both dipstick and urine culture, sensitivity and specificity for UTI were 87% (95% CI 78% to 93%) and 45% (95% CI 41% to 50%). Positive and negative predictive values were 21% (95% CI 17% to 26%) and 95% (95% CI 92% to 98%), whereas positive and negative likelihood ratios were 1.58 (95% CI 1.41 to 1.77) and 0.30 (95% CI 0.18 to 0.51). Pretest probabilities of UTI ranged from 29% to 60% in participants with specific UTI symptoms with corresponding post-test probabilities of 35-69% if dipsticks were positive and 12-27% if dipsticks were negative. Results remained comparable if final clinical diagnosis was used as outcome among all patients examined with dipsticks. Modified Poisson regression yielded an adjusted relative risk of 4.41 (95% CI 2.40 to 8.11) for empirical antibiotics for UTI in participants without specific UTI symptoms and a positive dipstick. CONCLUSIONS: Dipsticks yielded limited clinical decision support compared with a symptom-driven approach in this study and were independently associated with excess antibiotics for UTI.

The rRNA epitranscriptome and myonuclear SNORD landscape in skeletal muscle fibers contributes to ribosome heterogeneity and is altered by hypertrophic stimulus.

In cell biology, ribosomal RNA (rRNA) 2'O-methyl (2'-O-Me) is the most prevalent post-transcriptional chemical modification contributing to ribosome heterogeneity. The modification involves a family of small nucleolar RNAs (snoRNAs) and is specified by box C/D snoRNAs (SNORDs). Given the importance of ribosome biogenesis for skeletal muscle growth, we asked if rRNA 2'-O-Me in nascent ribosomes synthesized in response to a growth stimulus is an unrecognized mode of ribosome heterogeneity in muscle. To determine the pattern and dynamics of 2'-O-Me rRNA, we used a sequencing-based profiling method called RiboMeth-seq. We applied this method to tissue-derived rRNA of skeletal muscle and rRNA specifically from the muscle fiber using an inducible myofiber-specific RiboTag mouse in sedentary and mechanically overloaded conditions. These analyses were complemented by myonuclear-specific small RNA sequencing to profile SNORDs and link the rRNA epitranscriptome to known regulatory elements generated within the muscle fiber. We demonstrate for the first time that mechanical overload of skeletal muscle 1) induces decreased 2'-O-Me at a subset of skeletal muscle rRNAand 2) alters the SNORD profile in isolated myonuclei. These findings point to a transient diversification of the ribosome pool via 2'-O-Me during growth and adaptation in skeletal muscle. These findings suggest changes in ribosome heterogeneity at the 2'-O-Me level during muscle hypertrophy and lay the foundation for studies investigating the functional implications of these newly identified "growth-induced" ribosomes.

Prevalence and Risk Factors of Multitype Post-COVID Pain in a Cohort of Previously Hospitalized COVID-19 Survivors: A Danish Cross-Sectional Survey.

This population-based study investigated the prevalence of de novo, multitype, post-coronavirus disease (COVID) pain and its associated risk factors in previously hospitalized coronavirus disease 2019 (COVID-19) survivors. The nationwide, cross-sectional study included a cohort of Danish residents previously hospitalized due to severe acute respiratory syndrome coronavirus-2 infection between March 2020 and December 2021. Demographic data, preexisting medical comorbidities, previous pain-related symptoms, medication use for pain management, pain intensity (4-point scale), and development of de novo, multitype, post-COVID pain were collected by a self-reported survey distributed via e-Boks (a secured national digital mail system used in Denmark to provide public information to residents). The sample comprised 4,712 previously hospitalized COVID-19 survivors (48.6% women, mean age: 60.1 ± 15.6 years). At the time of the study (21 ± 6 months after hospitalization), 18.0% (847) reported the presence of de novo, multitype, post-COVID pain, and 38.6% of any pain. A multivariate analysis revealed that female sex (Odds Ratio (OR) 1.711, 95% Confidence Interval (CI) 1.444-2.023), higher body mass index (OR 1.032, 95% CI 1.019-1.045), intensive care unit admission (OR 1.597, 95% CI 1.324-1.926), previous history of whiplash (OR 2.471, 95% CI 1.004-6.081), anxiety (OR 3.626, 95% CI 1.335-9.708), and younger age (OR .982, 95% CI .976-.987) were factors associated with development of de novo, multitype, post-COVID pain. High income (OR .635, 95% CI .494-.817) and high educational level (OR .774, 95% CI .609-.984) were protective factors. In conclusion, multitype pain as a de novo post-COVID symptom was present in 18.0% of previously hospitalized COVID-19 survivors more than 1 year after hospital discharge and as such can be considered as adding to the global burden of chronic pain. PERSPECTIVE: The study investigates the prevalence of de novo, multitype, post-COVID pain in previously hospitalized COVID-19 survivors. This article presents potential risk factors associated with developing new pain symptoms. The results will contribute to understanding the possibility of predicting postinfectious pain from COVID-19 for future analysis.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

OBJECTIVES: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. METHODS: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. RESULTS: A total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. CONCLUSION: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

Validation of a risk score to differentiate autoimmune and viral encephalitis: a Nationwide Cohort Study in Denmark.

BACKGROUND: A score to differentiate autoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to evaluate the performance of the score in a larger and more diagnostically diverse patient cohort. METHODS: We conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015-2022) or autoimmune aetiology (2009-2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC). RESULTS: A total of 496 patients with encephalitis [AE n = 90, VE n = 287 and presumed infectious encephalitis (PIE) n = 119] were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92-0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84-0.93). CONCLUSION: The excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.

Lessons learnt on patient safety in dentistry through a 5-year nationwide database study on iatrogenic harm.

Safe delivery of care is a priority in dentistry, while basic epidemiological knowledge of patient safety incidents is still lacking. The objectives of this study were to (1) classify patient safety incidents related to primary dental care in Denmark in the period 2016-2020 and study the distribution of different types of dental treatment categories where harm occurred, (2) clarify treatment categories leading to "nerve injury" and "tooth loss" and (3) assess the financial cost of patient-harm claims. Data from the Danish Dental Compensation Act (DDCA) database was retrieved from all filed cases from 1st January 2016 until 31st December 2020 pertaining to: (1) The reason why the patient applied for treatment-related harm compensation, (2) the event that led to the alleged harm (treatment category), (3) the type of patient-harm, and (4) the financial cost of all harm compensations. A total of 9069 claims were retrieved, of which 5079 (56%) were found eligible for compensation. The three most frequent categories leading to compensation were "Root canal treatment and post preparation"(n = 2461, 48% of all approved claims), "lack of timely diagnosis and initiation of treatment" (n = 905, 18%) and "surgery" (n = 878, 17%). Damage to the root of the tooth accounted for more than half of all approved claims (54.36%), which was most frequently a result of either parietal perforation during endodontic treatment (18.54%) or instrument fracture (18.89%). Nerve injury accounted for 16.81% of the approved claims. Total cost of all compensation payments was €16,309,310, 41.1% of which was related to surgery (€6,707,430) and 20.4% (€3,322,927) to endodontic treatment. This comprehensive analysis documents that harm permeates all aspects of dentistry, especially in endodontics and surgery. Neglect or diagnostic delays contribute to 18% of claims, indicating that harm does not solely result from direct treatment. Treatment harm inflicts considerable societal costs.

DeepLoc 2.1: multi-label membrane protein type prediction using protein language models.

DeepLoc 2.0 is a popular web server for the prediction of protein subcellular localization and sorting signals. Here, we introduce DeepLoc 2.1, which additionally classifies the input proteins into the membrane protein types Transmembrane, Peripheral, Lipid-anchored and Soluble. Leveraging pre-trained transformer-based protein language models, the server utilizes a three-stage architecture for sequence-based, multi-label predictions. Comparative evaluations with other established tools on a test set of 4933 eukaryotic protein sequences, constructed following stringent homology partitioning, demonstrate state-of-the-art performance. Notably, DeepLoc 2.1 outperforms existing models, with the larger ProtT5 model exhibiting a marginal advantage over the ESM-1B model. The web server is available at https://services.healthtech.dtu.dk/services/DeepLoc-2.1.

Longitudinal evaluation of SARS-CoV-2 T cell immunity over 2 years following vaccination and infection.

BACKGROUND: Within a year of the SARS-CoV-2 pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine induced immunity led to implementation of additional vaccine boosters. METHODS: This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2 vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 Spike-specific T cells were determined after each vaccine dose using the Activation Induced Markers (AIM) assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay. RESULTS: We found a significant increase in SARS-CoV-2 Spike-specific CD4+ and CD8+ T cell responses following the third dose of a SARS-CoV-2 mRNA vaccine as well as enhanced CD8+ T cell responses after the fourth dose. Further, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone. CONCLUSION: Our findings highlight the boosting effect on T cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T cell immunity although with reduced levels in the elderly.

Fecal microbiota is associated with extraintestinal manifestations in inflammatory bowel disease.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitney's test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p < .05) and included important health-associated bacteria, such as Agathobacter and Faecalibacterium. CONCLUSIONS: The fecal microbiota in IBD patients with EIMs is distinct from that in IBD patients without EIM and could be important for EIM pathogenesis.

Multi-strain probiotics during pregnancy in women with obesity influence infant gut microbiome development: results from a randomized, double-blind placebo-controlled study.

Probiotics have been described to influence host health and prevent the risk of obesity by gut microbiome (GM) modulation. In a randomized double-blinded placebo-controlled feasibility study, we investigated whether Vivomixx® multi-strain probiotics administered to 50 women with obesity during pregnancy altered the GM composition and perinatal health outcomes of their infants up to 9 months after birth. The mothers and infants were followed up with four visits after birth: at 3 d, and at 3, 6, and 9 months after delivery. The infants were monitored by anthropometric measurements, fecal sample analysis, and questionnaires regarding health and diet.The study setup after birth was feasible, and the women and infants were willing to participate in additional study visits and collection of fecal samples during the 9-month follow-up. In total, 47 newborns were included for microbiome analysis.Maternal prenatal Vivomixx® administration did not alter infant GM diversity nor differential abundance, and the probiotic strains were not vertically transferred. However, the infant GM exhibited a decreased prevalence of the obesity-associated genera, Collinsella, in the probiotic group and of the metabolic health-associated Akkermansia in the placebo group, indicating that indirect community-scale effects of Vivomixx® on the GM of the mothers could be transferred to the infant.Moreover, 3 d after birth, the GM of the infant was influenced by mode of delivery and antibiotics administered during birth. Vaginally delivered infants had increased diversity and relative abundance of the metabolic health-associated Bifidobacterium and Bacteroides while having a decreased relative abundance of Enterococcus compared with infants delivered by cesarean section. Maternal antibiotic administration during birth resulted in a decreased relative abundance of Bifidobacteriumin the GM of the infants. In conclusion, this study observed potential effects on obesity-associated infant GM after maternal probiotic supplementation.

Update and approach to patients with brain abscess.

PURPOSE OF REVIEW: The epidemiology of brain abscess has changed in recent decades. Moreover, acute and long-term management remains challenging with high risks of mortality and neurological sequelae. This review describes recent advances in epidemiology, diagnosis, and treatment of brain abscess. RECENT FINDINGS: The incidence of brain abscess is increasing, especially among elderly individuals. Important predisposing conditions include dental and ear-nose-throat infections, immuno-compromise, and previous neurosurgery. Molecular-based diagnostics have improved our understanding of the involved microorganisms and oral cavity bacteria including anaerobes are the predominant pathogens. The diagnosis relies upon a combination of magnetic resonance imaging, neurosurgical aspiration or excision, and careful microbiological examinations. Local source control by aspiration or excision of brain abscess combined with long-term antimicrobials are cornerstones of treatment. Long-term management remains important and should address neurological deficits including epilepsy, timely diagnosis and management of comorbidities, and potential affective disorders. SUMMARY: A multidisciplinary approach to acute and long-term management of brain abscess remains crucial and source control of brain abscess by neurosurgery should be pursued whenever possible. Numerous aspects regarding diagnosis and treatment need clarification. Nonetheless, our understanding of this complicated infection is rapidly evolving.

RoBétArmé Project: Human-robot collaborative construction system for shotcrete digitization and automation through advanced perception, cognition, mobility and additive manufacturing skills.

The importance of construction automation has grown worldwide, aiming to deliver new machineries for the automation of roads, tunnels, bridges, buildings and earth-work construction. This need is mainly driven by (i) the shortage and rising costs of skilled workers, (ii) the tremendous increased needs for new infrastructures to serve the daily activities and (iii) the immense demand for maintenance of ageing infrastructure. Shotcrete (sprayed concrete) is increasingly becoming popular technology among contractors and builders, as its application is extremely economical and flexible as the growth in construction repairs in developed countries demand excessive automation of concrete placement. Even if shotcrete technology is heavily mechanized, the actual application is still performed manually at a large extend. RoBétArméEuropean project targets the Construction 4.0 transformation of the construction with shotcrete with the adoption of breakthrough technologies such as sensors, augmented reality systems, high-performance computing, additive manufacturing, advanced materials, autonomous robots and simulation systems, technologies that have already been studied and applied so far in Industry 4.0. The paper at hand showcases the development of a novel robotic system with advanced perception, cognition and digitization capabilities for the automation of all phases of shotcrete application. In particular, the challenges and barriers in shotcrete automation are presented and the RoBétArmésuggested solutions are outlined. We introduce a basic conceptual architecture of the system to be developed and we demonstrate the four application scenarios on which the system is designated to operate.

The RoBétArmé European project targets the Construction 4.0 transformation of the construction with shotcrete with the adoption of breakthrough technologies such as sensors, augmented reality systems, high-performance computing, additive manufacturing, advanced materials, autonomous robots and simulation systems, technologies that have already been studied and applied so far in Industry 4.0. This paper showcases a case study on which novel robotic systems will be developed for the automation of shotecrete application. The outcomes of this research can be widely used in other application technologies related to the construction domain.

JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms.

BACKGROUND: Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady-state hematopoiesis. METHODS: We analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next-generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre-MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub-diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub-diagnoses and MPN mutation. RESULTS: MPN patients had a higher observed richness (median, 245 [range, 49-659]) compared with HCs (191.5 [range, 111-300; p = .003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p < .001). The microbiota of CALR-positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F-positive patients, only minor differences in the gut microbiota were observed between MPN sub-diagnoses, illustrating the importance of this mutation. CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

Brain Abscess Caused by Oral Cavity Bacteria: A Nationwide, Population-based Cohort Study.

BACKGROUND: Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce. METHODS: We performed a nationwide, population-based study comprising all adults (aged ≥18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1-4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Among 287 identified patients, the median age was 58 years (interquartile range, 47-66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear-nose-throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53-7.04), rupture (RR, 1.89; 95% CI, 1.34-2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29-2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36-.93). CONCLUSIONS: Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.

Pulmonary arteriovenous malformations in patients with previous brain abscess: a cross-sectional population-based study.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. METHODS: This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). RESULTS: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. CONCLUSIONS: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.

Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.