BACKGROUND: Suspected infection or inflammation of unknown origin in in-patients remains challenging. Literature on [18F]FDG-PET/CT is abundant in classic fever of unknown origin (FUO), but evidence is complex and may not always reflect clinical reality. This study explores the application of [18F]FDG-PET/CT in a diverse clinical population of in-patients with suspected infection not defined by stringent FUO-criteria.
METHODS: Retrospective chart review of consecutive in-patients who underwent [18F]FDG-PET/CT in the workup of suspected infection or inflammation from 1 July 2022 to 31 December 2022 was conducted. We evaluated indications, diagnostic yield, and clinical impact of [18F]FDG-PET/CT, and compared the findings of [18F]FDG-PET/CT and stand-alone CT. Univariate logistic regression assessed associations between [18F]FDG-PET/CT outcome and clinical parameters. Receiver operating characteristic curve (ROC) analysis evaluated diagnostic performance.
RESULTS: 77 patients met the inclusion criteria. [18F]FDG-PET/CT established a diagnosis in 35% of cases, ruled out focal infection in 26%, and thus was helpful in 61% of patients. It prompted 72 additional examinations resulting in seven incidental diagnoses, including two cancers. Antibiotic treatment was changed in 26% of cases. Regression analysis found white blood cell counts (WBC) associated with true positive outcomes. [18F]FDG-PET/CT was compared to stand-alone CT findings, and was concordant in 69% of cases.
CONCLUSIONS: Results were comparable to findings in more classic FUO. [18F]FDG-PET/CT was clinically helpful in 61% of cases but also prompted many additional examinations with relatively few clinically important findings. WBC count was a predictor of true positive outcome. CT and [18F]FDG-PET/CT were discordant in 31%, of cases, especially in cases of endocarditis and spondylodiscitis.

BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center.
METHODS: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described.
RESULTS: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin\'s lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still\'s disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis.
CONCLUSIONS: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

UNASSIGNED: FDG PET/CT is a well-documented imaging investigation to evaluate fever of unknown origin (FUO). Brucellosis is one of the causes of FUO, which can be missed as it requires a longer incubation period for growth on culture media. Rarely, it can involve the prostate. Here, we present a case of FUO with initial negative blood and urine cultures and no localizing signs or symptoms. 18F-FDG PET/CT revealed hypermetabolism in the prostate and seminal vesicles. A repeat blood and urine culture showed the growth of Brucella species after 5 days of incubation, and the patient responded to Brucella-directed antibiotic therapy.

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.

Still\'s disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.
METHODS: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient\'s condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.
CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

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BACKGROUND: Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources.
OBJECTIVE: To identify the probable etiology of AUF through inflammatory markers.
OBJECTIVE: To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF.
METHODS: This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21.
RESULTS: The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes.
CONCLUSIONS: Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.

Melioidosis, an emerging infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is massively underdiagnosed in many low- and middle-income countries. The disease is clinically extremely variable, has a high case fatality rate, and is assumed to be highly endemic in South Asian countries, including Nepal. The reasons for underdiagnosis include the lack of awareness among clinicians and laboratory staff and limited microbiological capacities. Because costly laboratory equipment and consumables are likely to remain a significant challenge in many melioidosis-endemic countries in the near future, it will be necessary to make optimum use of available tools and promote their stringent implementation. Therefore, we suggest that health facilities in resource-poor countries, such as Nepal, introduce a simple and low-cost diagnostic laboratory algorithm for the identification of B. pseudomallei cultures. This screening algorithm should be applied specifically to samples from patients with fever of unknown origin and risk factors for melioidosis, such as diabetes. In addition, there could also be a role of low-cost, novel, promising serological point-of-care tests, which are currently under research and development.

OBJECTIVE: This study aimed to evaluate the potential role of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in providing a targeted approach for diagnosing the etiology of Pyrexia of Unknown Origin (PUO).
METHODS: A total of 573 PUO patients were included in this ambispective study, with a mean age of 39.40 ± 4.6 years. Patients underwent FDG PET/CT scans using dedicated hybrid scanners. PET/CT data were interpreted by experienced nuclear medicine physicians. The study analyzed the guidance provided by FDG PET/CT for appropriate biopsy sites and assessed concordance between PET/CT findings and histopathological examination.
RESULTS: Out of the 573 patients, a final diagnosis was reached for 219 patients, including malignancy, infectious causes, noninfectious inflammatory causes (NIID), and precancerous conditions. FDG PET/CT played a crucial role in guiding clinicians to appropriate biopsy sites, contributing to a higher diagnostic yield. Concordance between PET/CT findings and histopathological examination emphasized the noninvasive diagnostic potential of PET/CT in identifying underlying causes of PUO. Overall, FDG PET/CT contributed to guiding the appropriate site of biopsy or concordance of the first differential diagnosis with the final diagnosis in 50.05% of cases.
CONCLUSIONS: This study highlights the valuable role of FDG PET/CT in providing a targeted approach for diagnosing PUO, showcasing its potential in guiding clinicians towards appropriate biopsy sites and improving the diagnostic yield. The findings underscore the importance of integrating FDG PET/CT into the diagnostic pathway for PUO, ultimately enhancing patient management and outcomes. Further prospective studies are necessary to validate these results and refine the integration of FDG PET/CT in the diagnosis of PUO.