Predictors of Diagnostic Contributions and Spontaneous Remission of Symptoms Associated with Positron Emission Tomography with Fluorine-18-Fluorodeoxy Glucose Combined with Computed Tomography in Classic Fever or Inflammation of Unknown Origin: a Retrospective Study.

BACKGROUND: In patients with fever or inflammation of unknown origin (fever of unknown origin [FUO] or inflammation of unknown origin [IUO], respectively), expert consensus recommends the use of positron emission tomography with fluorine-18-fluorodeoxy glucose combined with computed tomography (FDG-PET/CT) when standard work-up fails to identify diagnostic clues. However, the clinical variables associated with successful localization of the cause by FDG-PET/CT remain uncertain. Moreover, the long-term outcomes of patients with unexplained FUO or IUO after negative FDG-PET/CT results are unknown. Therefore, we assessed predictors of successful diagnosis of FUO or IUO caused by FDG-PET/CT and associations of spontaneous remission of symptoms with FDG-PET/CT results. METHODS: All patients with FUO or IUO, who underwent FDG-PET/CT from 2013 to 2019 because diagnostic work-up failed to identify a cause, were retrospectively included. We calculated the diagnostic yield and performed multivariable logistic regression to assess characteristics previously proposed to be associated with successful localization of FUO or IUO causes. We also assessed whether the FDG-PET/CT results were associated with spontaneous remissions. RESULTS: In total, 50 patients with diagnostically challenging FUO or IUO (35 with FUO and 15 with IUO) were assessed. Other than one case of infection, all the identified causes were either malignancy or non-infectious inflammatory diseases (each with 18 patients), and FDG-PET/CT correctly localized the cause in 29 patients (diagnostic yield = 58%). None of the proposed variables was associated with successful localization. All 13 patients with sustained unexplained cause remained alive (median follow-up, 190 days). Spontaneous remission was observed in 4 of 5 patients with a negative FDG-PET/CT, and 1 of 8 with a positive result (P = 0.018). CONCLUSION: In the current cohort, the proposed variables were not predictive for successful localization by FDG-PET/CT. A negative FDG-PET/CT scan may be prognostic for spontaneous remission in patients with sustained FUO or IUO.

Long-term prognosis, treatment, and outcome of patients with fever of unknown origin in whom no diagnosis was made despite extensive investigation: A questionnaire based study.

In 30-50% of patients with fever of unknown origin (IUO) no explanation for the fever can be found. Prognosis and effects of empirical treatment of these patients are largely unknown.With this retrospective, questionnaire based corort study in all unexplained FUO patients in an expert center between 2003 and 2014 we studied mortality and outcome.In 131 of 274 FUO patients, FUO remained unexplained. Ninety-nine of them responded to the long-term follow up questionnaire. Adter a median duration of follow-up of 60 months, spontaneous remission of fever occured in 47.3%. Empirical treatment was effective in 66.7% of patients. Mortality was 6.9%. The cause of death was considered not to be related to the febrile disease in five out of six patients. Ten out of 99 responders reported to have received a final explanation for FUO after evaluation in the expertise center, but this diagnosis could not be confirmed in six cases and was considered to be an unlikely explanation for FUO in four out of six cases.We conclude that mortality in unexplained FUO is low en mostly unrelated to the febrile disease. Spontaneous resolution of fever is common. Empirical treatment prescribed by an expert physician is often effective, but should be avoided untill all diagnostic possibilities have been exhaused.

Early discontinuation of empirical antibacterial therapy in febrile neutropenia: the ANTIBIOSTOP study.

INTRODUCTION: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin (FUO). OBJECTIVES: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia. METHODS: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37). RESULTS: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia. CONCLUSIONS: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.

Mortality in patients presenting with fever of unknown origin.

BACKGROUND: Few data exist on the contemporary prognosis of patients presenting with fever of unknown origin (FUO). METHODS: The data of 436 adult immunocompetent patients presenting with FUO between 2000 and 2010 and followed for at least 6 months were analyzed, with a focus on FUO-related deaths. The following variables were assessed in survivors and non-survivors: age, underlying diagnosis, and, in a nested case-control design, fever periodicity, selected laboratory parameters (including peripheral blood counts, enzymes, and inflammatory markers) and organomegaly. RESULTS: Thirty FUO-related deaths occurred (6·9%). Malignancy accounted for 11% of fevers but for 60% of deaths. Especially non-Hodgkin lymphoma carried a disproportionally high death toll. In the non-malignant categories, fatality rates were below 6%. All patients discharged without diagnosis in spite of ample investigations (n = 164) survived. Besides malignancy, age, continuous (as opposed to episodic) fever, anaemia, leucopenia, LDH levels, and hepatomegaly were associated with mortality. CONCLUSIONS: Fatality rates of FUO have continuously declined over the past decades. Malignancy, including lymphoma, remains a cardinal cause of death. Patients with FUO discharged without diagnosis survive.

Effectiveness of a Protective Environment implementation for cancer patients with chemotherapy-induced neutropenia on fever and mortality incidence.

In a quasiexperimental study conducted to evaluate the impact of a Protective Environment implementation, febrile neutropenia (P = .009), overall mortality (P = .001), and 30-day adjusted mortality (P = .02) were reduced in cancer patients with chemotherapy-induced neutropenia. Our study highlights the potential success of a set of prevention measures mainly designed to reduce invasive environmental fungal infections in allogeneic hematopoietic stem cell transplant patients, in reducing fever and mortality among neutropenic cancer patients.

Fever with rash in a child in India.

Fever with rash is common among children and are seen by both dermatologists and pediatricians. Most of them are benign viral exanthems without much clinical significance. This article gives an overview of the infectious and noninfectious causes of fever with rash in children and how to diagnose them, with special emphasis on the Indian scenario as well. It also differentiates them from fever with rash caused by drugs. This review emphasizes that although benign in many cases, it is necessary to identify the signs of serious illnesses to prevent mortality or sequelae.

Old and new biomarkers for predicting high and low risk microbial infection in critically ill patients with new onset fever: a case for procalcitonin.

OBJECTIVES: Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever. METHODS: We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses. RESULTS: All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor. CONCLUSIONS: In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL.

Comparison of mortality between nosocomial and community-acquired febrile neutropenia patients treated initially with cefazolin plus tobramycin: retrospective chart review.

Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002-2004 to 13% in 2008-2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.

Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study.

Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram-negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non-susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis.

Is cefepime safe for clinical use? A Bayesian viewpoint.

Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338-48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08-1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that 'data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.' However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections.

Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP).

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 µg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

Neutrophil CD64: diagnostic accuracy and prognostic value in patients presenting to the emergency department.

The purpose of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil CD64 expression for bacterial infection in febrile adult patients presenting to our hospital emergency department. We prospectively included 132 patients with fever ≥ 38ºC (≥ 100.4ºF) during the last 24 hours and we measured CD64 expression on neutrophils the day after admission at the emergency department. We followed the patients until full recovery or death. There were 115 (87%) patients with bacterial infection and 108 (94%) of them survived. There were 17 (13%) patients without bacterial infection and 12 (71%) of them survived. Patients with bacterial infection and patients who survived showed a CD64 index higher when compared with patients without bacterial infection and patients who died, respectively (3.7 ± 3.2 vs. 2.5 ± 2.3; p = 0.03; and 3.7 ± 3.1 vs. 1.7 ± 0.6; p = 0.002; Mann-Whitney U test). The receiver operating characteristic (ROC) curve analysis for detecting bacterial infection and predicting survival with the CD64 index showed an area under curve (AUC) of 0.66 (95% CI, 0.52-0.8; p = 0.03) and 0.71 (95% CI, 0.57-0.85; p = 0.01), respectively. Diagnostic accuracy and prognostic value of CD64 expression was good in adult patients with fever.

Systematic review and mixed treatment comparison of randomized evidence for empirical, pre-emptive and directed treatment strategies for invasive mould disease.

Randomized controlled trials (RCTs) provide the most reliable estimates of the effects of treatments. However, not all treatments are compared in available RCTs, making comparison of treatments problematic. Mixed treatment comparisons (MTCs) can provide estimates of the comparative effects of treatments across a range of available therapeutic options. MTCs use networks of available direct comparisons to estimate differences in treatments that have not been estimated in trials via a common comparator. We conducted a systematic review and MTCs of comparative RCTs in haematological patients of anti-mould active agents used for the empirical treatment of febrile neutropenia (Analysis 1), and pre-emptive therapy (Analysis 2) of invasive mould diseases. In addition, we summarized the evidence available associated with the use of directed treatment strategies (Analysis 3). For empirical therapy, caspofungin proved superior to amphotericin B, liposomal amphotericin B, amphotericin B lipid complex and voriconazole in the outcome of survival, but no agents showed superiority for treatment response. There was no evidence of a difference between pre-emptive and empirical strategies on mortality outcomes. For directed therapy, voriconazole was superior to amphotericin B for overall survival, and both voriconazole and liposomal amphotericin B were superior to amphotericin B and amphotericin B colloidal dispersion on the outcome of response. While limited to some degree by the availability of RCTs, the MTCs reported here provide the best available evidence of relative therapeutic success for different available treatment strategies.

Meta-analysis of a possible signal of increased mortality associated with cefepime use.

BACKGROUND: On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials. METHODS: We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method. RESULTS: The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21). CONCLUSIONS: In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials.

Inflammation of unknown origin versus fever of unknown origin: two of a kind.

OBJECTIVES: A vast literature exists on fever of unknown origin (FUO), characterized by prolonged and perplexing fevers >38.3 degrees C. In contrast, no studies are available to guide the approach to inflammation of unknown origin (IUO), defined as prolonged and perplexing inflammation with temperatures <38.3 degrees C. We aimed to determine the diagnostic yield, the case-mix, and the outcome of patients with IUO, relative to patients with FUO. METHODS: We matched 57 patients with IUO to 57 patients with FUO of the same gender (54% male) and a similar age (median: 67 years). RESULTS: A diagnosis was established in 35 patients with IUO (61%) and in 33 patients with FUO (58%) (p=.70). The case-mix did not differ significantly (p=.43). Non-infectious inflammatory disorders were the dominant diagnostic category in the IUO group (16 patients), while in the FUO group, similar numbers of malignancies [10], infections [9], and non-infectious inflammatory diseases [9] were diagnosed. (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan contributed comparably to the diagnosis in both groups (in 18 of 50, 36%, patients with IUO and in 13 of 40, 33%, patients with FUO) (p=.83). In both groups, 7 patients (12%) died during an average follow-up of 1 year. CONCLUSION: Diagnostic yield, case-mix, contribution of FDG-PET scan and vital outcome were similar in patients with IUO and FUO. These data suggest that the 38.3 degrees C boundary may be arbitrary and that the diagnostic approaches used in FUO can be applied to IUO.

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland.

BACKGROUND: Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic. METHODS: Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods. RESULTS: 7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis. CONCLUSION: Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

Diagnostic splenectomy in patients with fever of unknown origin and splenomegaly.

OBJECTIVE: To review the diagnostic significance, safety and possible risk factors of splenectomy in fever of unknown origin (FUO) with splenomegaly. METHODS: The records of 54 patients with FUO and splenomegaly who underwent splenectomy in our hospital in the past 20 years were reviewed retrospectively. Pathologic findings, morbidity, mortality and possible risk factors were analyzed. RESULTS: Histologic findings included 29 cases of non-Hodgkin lymphoma, 4 cases of spleen tuberculosis, 3 cases of Hodgkin lymphoma, 1 case of Castleman disease and 2 cases of hemophagocytic syndrome. An etiologic diagnosis was made in 72.2% of the patients undergoing splenectomy. Surgical complications occurred in 25.9% of the patients and 1-month operative mortality was 16.7%. The mortality rate 1 month after surgery was significantly associated with serous cavity effusion (46.2 vs. 7.5%, p = 0.006) and spleen weight >1,500 g (50.0 vs. 9.1%, p = 0.007). There was no significant difference in the mortality rate of the patients with or without jaundice, pancytopenia, elevated serum alanine aminotransferase (ALT) or elevated LDH (p > 0.5). Multivariate analysis revealed serous cavity effusion (odds ratio 21.0; 95% confidence interval 2.2-212.8; p = 0.01) and spleen weight >1,500 g (odds ratio 18.0; 95% confidence interval 1.9-173.8; p = 0.01) as independent risk factors. CONCLUSION: Splenectomy is an effective diagnostic modality for FUO presenting with splenomegaly. The presence of serous cavity effusions and spleen weight >1,500 g identifies patients with the greatest operative risk.

A retrospective review of 226 hospitalized patients with fever.

OBJECTIVE: To describe characteristics and outcomes for patients hospitalized with fever, not only patients with fever of unknown origin (FUO). METHODS: Medical records were reviewed for 226 consecutive patients hospitalized in a Japanese referral hospital with fever as one of the clinical problems. RESULTS: Although the majority of illnesses involved some sort of infection (54%), noninfectious inflammatory diseases, particularly adult Still's disease (n=6) and primary vasculitis syndromes (n=5) including 3 cases of Behçet's disease, represented the leading cause in patients who met the definition of FUO [16/51(31%)]. Tuberculosis (n=6) and psychological disorders (n=6) were associated with late diagnosis. However, there was only one patient meeting the definition of FUO among those with a psychological disorder. Among the patients with prolonged fever who did not strictly meet the definition of FUO, there was a considerable number of patients with critical illnesses, such as intra-abdominal abscess, polymyalgia rheumatica, sarcoidosis, ulcerative colitis, Castleman's disease, hematological and solid malignancies, and panhypopituitarism. Drug-induced fever, systemic viral infection and unspecified vasculitis were difficult to definitively diagnose, although these pathologies were suspected as causes of fever. Follow-up of patients without definitive diagnosis at discharge confirmed that the fever subsided spontaneously or the cause of fever was properly treated after diagnosis in every patient and that none died of the underlying febrile illness. CONCLUSIONS: The present findings, from all patients displaying fever at hospitalization, are in agreement with findings from prior FUO series. Strict use of the definition of FUO is thus unwarranted when managing patients with prolonged fever.