UNASSIGNED: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients.
UNASSIGNED: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies.
UNASSIGNED: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO.
UNASSIGNED: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

OBJECTIVE: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [18F]FDG-PET/CT in FUO and IUO based on current evidence.
METHODS: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with \"patients with FUO/IUO\" as population, \"[18F]FDG-PET/CT\" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness.
RESULTS: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations.
CONCLUSIONS: FUO and IUO remains a clinical challenge and [18F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections.
CONCLUSIONS: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment.
BACKGROUND: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice.
BACKGROUND: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections.

With a growing emphasis on value-based reimbursement, developing quality indicators for infectious diseases has gained attention. Quality indicators for fever of unknown origin and inflammation of unknown origin are lacking. An assembled group of international experts developed 12 quality measures for these conditions, which could be validated with additional study.

BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described.
METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children\'s Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations.
RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed.
CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.

Fever without a source (FWS) in children poses a diagnostic challenge. To distinguish a self-limiting infection from a serious infection, multiple guidelines have been developed to aid physicians in the management of FWS. Currently, there is no comparison of existing FWS guidelines.
This comparative review describes consistencies and differences in guideline definitions and diagnostic and therapeutic recommendations. A literature search was performed to include secondary care FWS guidelines of high-income countries, composed by national or regional pediatric or emergency care associations, available in English or Dutch.
Ten guidelines of five high-income countries were included, with varying age ranges of children with FWS. In children younger than one month with FWS, the majority of the guidelines recommended laboratory testing, blood and urine culturing and antibiotic treatment irrespective of the clinical condition of the patient. Recommendations for blood culture and antibiotic treatment varied for children aged 1-3 months. In children aged above three months, urine culture recommendations were inconsistent, while all guidelines consistently recommended cerebral spinal fluid testing and antibiotic treatment exclusively for children with a high risk of serious infection.
We found these guidelines broadly consistent, especially for children with FWS younger than one month. Guideline variation was seen most in the targeted age ranges and in recommendations for children aged 1-3 months and above three months of age. The findings of the current study can assist in harmonizing guideline development and future research for the management of children with FWS.

The Dutch fever without an apparent source (FWS) guidelines were published to timely recognize and treat serious infections. We determined the adherence to the Dutch FWS guidelines and the percentage of serious infections in infants younger than 3 months of age. Second, we identified which clinical criteria, diagnostic tests, and management were associated with nonadherence to the guidelines.
A retrospective cohort study was performed in 2 Dutch teaching hospitals. We assessed the charts of all infants with FWS who presented at the emergency departments from September 30, 2017, to October 1, 2019. Diagnostic and therapeutic decisions were compared with the recommendations, as published in the Dutch guidelines. Infants were categorized into the nonadherence group in case 1 or more recommendations were not adhered to.
Data on 231 infants were studied; 51.5% of the cases adhered to the Dutch guidelines and 16.0% suffered from a serious infection. The percentage of infants with a serious infection was higher in the adherence compared with the nonadherence group. We observed no relevant differences in clinical outcomes. Univariate regression analysis showed that an abnormal white blood cell count was associated with nonadherence (OR 0.4, P = 0.049). Not obtaining a urine and blood culture and not starting intravenous antibiotic treatment were the most frequent reasons for nonadherence to the guidelines.
Our study indicates that there was nonadherence in a large proportion of FWS cases. The guidelines may need to be adjusted to increase adherence.

Whole-body MRI is an imaging method that uses advanced modern MRI equipment to provide high-resolution images of the entire body. The goal of these guidelines is to specify the indications for which whole-body MRI can be recommended in children and adolescents and to describe the necessary technical requirements. CITATION FORMAT: · Schaefer JF, Berthold LD, Hahn G et al. Whole-Body MRI in Children and Adolescents - S1 Guidelines. Fortschr Röntgenstr 2019; 191: 618 - 625.
Die Ganzkörper-Magnetresonanztomografie (GK-MRT) ist eine bildgebende Methode, welche unter Nutzung fortgeschrittener Verfahren moderner MRT-Geräte eine hochaufgelöste Darstellung des gesamten Körpers ermöglicht. Ziel dieser Leitlinie ist es, Indikationen zu benennen, bei denen die GK-MRT im Kindes- und Jugendalter empfohlen werden kann, und dafür notwendige, technische Voraussetzungen zu beschreiben. ZITIERWEISE: · Schaefer JF, Berthold LD, Hahn G et al. Whole-Body MRI in Children and Adolescents – S1 Guidelines. Fortschr Röntgenstr 2019; 191: 618 – 625.

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.

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