Liver cyst infections often necessitate long-term hospital admission and are associated with considerable morbidity and mortality. We conducted a modified Delphi study to reach expert consensus for a clinical decision framework. The expert panel consisted of 24 medical specialists, including 12 hepatologists, from nine countries across Europe, North America, and Asia. The Delphi had three rounds. The first round (response rate 21/24 [88%]) was an online survey with questions constructed from literature review and expert opinion, in which experts were asked about their management preferences and rated possible management strategies for seven clinical scenarios. Experts also rated 14 clinical decision-making items for relevancy and defined treatment outcomes. During the second round (response rate 13/24 [54%]), items that did not reach consensus and newly suggested themes were discussed in an online panel meeting. In the third round (response rate 16/24 [67%]), experts voted on definitions and management strategies using an online survey based on previous answers. Consensus was predefined as a vote threshold of at least 75%. We identified five subclassifications of liver cyst infection according to cyst phenotypes and patient immune status and consensus on episode definitions (new, persistent, and recurrent) and criteria for treatment success or failure was reached. The experts agreed that fever and elevated C-reactive protein are pivotal decision-making items for initiating and evaluating the management of liver cyst infections. Consensus was reached on 26 management statements for patients with liver cyst infections across multiple clinical scenarios, including two treatment algorithms, which were merged into one after comments. We provide a clinical decision framework for physicians managing patients with liver cyst infections. This framework will facilitate uniformity in the management of liver cyst infections and can constitute the basis for the development of future guidelines.

Rationale: Patients with chronic intestinal failure (CIF) require a central venous access device (CVAD) to administer (home) parenteral nutrition. Central line-associated bloodstream infections (CLABSIs) are the most daunting complication associated with such CVADs. Blood cultures remain the gold standard to diagnose CLABSIs, but take 1-5 days to become positive and guide antibiotic treatment. ddPCR is a novel culture-independent molecular technique that has been developed to improve and expedite infection diagnostics, yielding results within 4 hours. Here, we compare ddPCR and blood culture characteristics of pathogen detection in whole-blood.

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Background: For surgical treatment of primary aortic infection and aor tic graft infection, in situ reconstruction with autologous vein(s) has the lowest rates of re-infection and of graft thrombosis. In this study, we have assessed the outcome after autologous femoral vein reconstruction in patients with aortic (graft) infection and we provide insights into the specific technical surgical considerations of the procedure. Methods: In this retrospective single-center study, all patients who underwent autologous femoral vein reconstruction because of primary aortic infection or aortic graft infection between January 2012 and January 2020 were included. The primary outcome parameter was 30-day mortality. Results: Twenty-nine patients with autologous femoral vein reconstruction for a primary aortic infection (n = 3) or aortic graft infection (n = 26) were included. An aorto-enteral fistula was detected in 13 patients (49%). Venous reconstruction of the aorta was performed with a single femoral vein in 17 patients (59%), and two femoral veins in 12 patients (41%). Thirty-day mortality was 17%. Relapse of infection occurred in two patients (7%) and no amputations were needed. One year after surgery, only three patients (10%) still needed stockings and after 2 years none of the patients used stockings. Conclusions: Central aortic reconstruction with femoral veins is a durable solution for primary aortic and aor toiliac graft infections with a low incidence of reinfections, amputations, and venous hypertension.

Abstract Background We evaluated the success rate of MRSA decolonization directly after treatment and after one year in patients who were treated at the outpatient MRSA clinic of a large university medical centre to identify potential contributing factors to treatment success and failure. Methods Data from November 1, 2013 to August 1, 2020 were used. Only patients who had undergone complete MRSA decolonization were included. Risk factors for MRSA treatment failure were identified using a multivariable logistic regression model. Results In total, 127 MRSA carriers were included: 7 had uncomplicated carriage, 91 had complicated carriage, and 29 patients had complicated carriage in combination with an infection. In complicated carriers and complicated carriers with an infection final treatment was successful in 75.0%. Risk factors for initial treatment failure included having one or more comorbidities and not testing the household members. Risk factors for final treatment failure were living in a refugee centre, being of younger age (0–17 years), and having one or more comorbidities. Conclusions The results of this study indicate that patients with a refugee status and children treated at the paediatric clinic have a higher risk of MRSA decolonisation treatment failure. For this reason, it might be useful to revise decolonization strategies for these subgroups and to refer these patients to specialized outpatient clinics in order to achieve higher treatment success rates.

Objective: Detection of the intracellular bacterium Coxiella burnetii, causative agent of chronic Q fever, is notoriously difficult. Diagnosis of and duration of antibiotic treatment for chronic Q fever is partly determined by detection of the bacterium with polymerase chain reaction (PCR). Fluorescence in situ hybridization (FISH) might be a promising technique for detecting C. burnetii in tissue samples from chronic Q fever patients, but its value in comparison with PCR is uncertain. We aim to assess the value of FISH for detecting C. burnetii in tissue of chronic Q fever patients. Methods: FISH and PCR were performed on tissue samples from Dutch chronic Q fever patients collected during surgery or autopsy. Sensitivity, specificity, and overall diagnostic accuracy were calculated. Additionally, data on patient and disease characteristics were collected from electronic medical records. Results: In total, 49 tissue samples from mainly vascular walls, heart valves, or placentas, obtained from 39 chronic Q fever patients, were examined by FISH and PCR. The sensitivity and specificity of FISH compared to PCR for detecting C. burnetii in tissue samples from chronic Q fever patients was 45.2% (95% confidence interval (CI), 27.3% - 64.0%) and 84.6% (95% CI, 54.6% - 98.1%), respectively. The overall diagnostic accuracy was 56.8% (95% CI, 42.2% - 72.3%). Two C. burnetii PCR negative placentas were FISH positive. Four FISH results (8.2%) were deemed inconclusive because of autofluorescence. Conclusion: With an overall diagnostic accuracy of 57.8%, we conclude that FISH has limited value in the routine diagnostics of chronic Q fever. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

Background and aims: Patients with intestinal failure receiving home parenteral nutrition (HPN) are susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to decide on the safest and most accurate CLABSI management in patients receiving HPN. Methods: A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010-2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and empiric antimicrobial treatment (beta-lactam antibiotics) in our center, with a low prevalence of methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed to identify risk factors for recurrent CLABSI. Results: 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%). Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage. According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35-0.72, P < 0.001). Conclusions: CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment regimen will increase the likelihood of adequate empiric coverage. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

Background Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19. Methods In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged >= 60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. Results The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. Conclusions BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection. BCG vaccination did not protect older adults in a Western European country against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other respiratory tract infections. However, those subsequently infected with SARS-CoV-2 displayed higher antibody responses against SARS-CoV-2 than nonvaccinated individuals.

Background:Chronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue.Methods:Multiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune systems.Results:Q fever AAAs and atherosclerotic AAAs contained similar numbers of CD68+ macrophages and CD3+ T cells. However, in Q fever AAAs, the number of CD68+CD206+ M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8+ cytotoxic T cells and CD3+CD8-FoxP3+ regulatory T cells. Finally, Q fever AAAs did not contain any well-defined granulomas.Conclusions:These findings demonstrate that despite the presence of pro-inflammatory effector cells, persistent local infection with C. burnetii is associated with an immune-suppressed microenvironment.Funding:This work was supported by SCAN consortium: European Research Area - CardioVascualar Diseases (ERA-CVD) grant [JTC2017-044] and TTW-NWO open technology grant [STW-14716].

Background: the geographical similarities of the Dutch 2007–2010 Q fever outbreak and the start of the 2020 coronavirus disease 19 (COVID-19) outbreak in the Netherlands raised questions and provided a unique opportunity to study an association between Coxiella burnetii infection and the outcome following SARS-CoV-2 infection. Methods: We performed a retrospective cohort study in two Dutch hospitals. We assessed evidence of previous C. burnetii infection in COVID-19 patients diagnosed at the ED during the first COVID-19 wave and compared a combined outcome of in-hospital mortality and intensive care unit (ICU) admission using adjusted odds ratios (OR). Results: In total, 629 patients were included with a mean age of 68.0 years. Evidence of previous C. burnetii infection was found in 117 patients (18.6%). The combined primary outcome occurred in 40.2% and 40.4% of patients with and without evidence of previous C. burnetii infection respectively (adjusted OR of 0.926 (95% CI 0.605–1.416)). The adjusted OR of the secondary outcomes in-hospital mortality, ICU-admission and regular ward admission did not show an association either. Conclusion: no influence of previous C. burnetii infection on the risk of ICU admission and/or mortality for patients with COVID-19 presenting at the ED was observed.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

Background and Objectives The pathophysiology of chronic fatigue syndrome (CFS) and Q fever fatigue syndrome (QFS) remains elusive. Recent data suggest a role for neuroinflammation as defined by increased expression of translocator protein (TSPO). In the present study, we investigated whether there are signs of neuroinflammation in female patients with CFS and QFS compared with healthy women, using PET with the TSPO ligand 11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox-amide ([11C]-PK11195). Methods The study population consisted of patients with CFS (n = 9), patients with QFS (n = 10), and healthy subjects (HSs) (n = 9). All subjects were women, matched for age (±5 years) and neighborhood, aged between 18 and 59 years, who did not use any medication other than paracetamol or oral contraceptives, and were not vaccinated in the last 6 months. None of the subjects reported substance abuse in the past 3 months or reported signs of underlying psychiatric disease on the Mini-International Neuropsychiatric Interview. All subjects underwent a [11C]-PK11195 PET scan, and the [11C]-PK11195 binding potential (BPND) was calculated. Results No statistically significant differences in BPND were found for patients with CFS or patients with QFS compared with HSs. BPND of [11C]-PK11195 correlated with symptom severity scores in patients with QFS, but a negative correlation was found in patients with CFS. Discussion In contrast to what was previously reported for CFS, we found no significant difference in BPND of [11C]-PK11195 when comparing patients with CFS or QFS with healthy neighborhood controls. In this small series, we were unable to find signs of neuroinflammation in patients with CFS and QFS. Trial Registration Information EudraCT number 2014-004448-37.

Prolonged fever of 38.3 degrees C or higher for at least 3 weeks' duration has been termed fever of unknown origin if unexplained after preliminary investigations. Initially codified in 1961, classification with subgroups was revised in 1991. Additional changes to the definition were proposed in 1997, recommending a set of standardized initial investigations. Advances in diagnosis and management and diagnostic testing over the last 3 decades have prompted a needed update to the definition and approaches. While a 3-week fever duration remains part of the criteria, a lower temperature threshold of 38 degrees C and revised minimum testing criteria will assist clinicians and their patients, setting a solid foundation for future research. (c) 2021 Elsevier Inc. All rights reserved. center dot The American Journal of Medicine (2022) 135:173-178

Background: A causative role of Coxiella burnetii (the causative agent of Q fever) in the pathogenesis of B-cell non-Hodgkin lymphoma (NHL) has been suggested, although supporting studies show conflicting evidence. We assessed whether this association is present by performing a detailed analysis on the risk of mature B-cell NHL after Q fever during and after the largest Q fever outbreak reported worldwide in the entire Dutch population over a 16-year period. Methods: We performed an ecological analysis. The incidence of mature B-cell NHL in the entire Dutch population from 2002 until 2017 was studied and modelled with reported acute Q fever cases as the determinant. The adjusted relative risk of NHL after acute Q fever as the primary outcome measure was calculated using a Poisson regression. Results: Between January 2002 and December 2017, 266 050 745 person-years were observed, with 61 424 diagnosed with mature B-cell NHL. In total, 4310 persons were diagnosed with acute Q fever, with the highest incidence in 2009. The adjusted relative risk of NHL after acute Q fever was 1.02 (95% CI 0.97-1.06, P = 0.49) and 0.98 (95% CI 0.89-1.07, P = 0.60), 0.99 (95% CI 0.87-1.12, P = 0.85) and 0.98 (95% 0.88-1.08, P = 0.67) for subgroups of diffuse large B-cell lymphoma, follicular lymphoma or B-cell chronic lymphocytic leukaemia, respectively. Modelling with lag times (1-4 years) did not change interpretation. Conclusion: We found no evidence for an association between C. burnetii and NHL after studying the risk of mature B-cell NHL after a large Q fever outbreak in Netherlands.

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.

SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.