UNASSIGNED: Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO.
UNASSIGNED: Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China.
UNASSIGNED: The causes of FUO with the highest rates from the 51 identified case series (n = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, n = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% vs. 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% vs. 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still\'s disease among autoimmune diseases (4.6% vs. 8.5%) and lung cancer among neoplastic diseases (0.6% vs. 1.6%).
UNASSIGNED: Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.

Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient\'s fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

A 48-year-old male was admitted to Peking Union Medical College Hospital presented with intermittent fever for two years. The maximum body temperature was 39 ℃, and could spontaneously relieve. The efficacy of antibacterial treatment was poor. He had no other symptoms and positive signs. He had a significant weight loss, and the serum lactate dehydrogenase increased significantly. It was highly alert to be lymphoma, but bone marrow smear and pathology, and PET-CT had not shown obvious abnormalities. Considering high inflammatory indicators, increased ferritin and large spleen, the patient had high inflammatory status, and was treated with methylprednisolone. Then the patient\'s body temperature was normal, but the platelet decreased to 33×109/L. During hospitalization, he had suddenly hemoperitoneum and hemorrhagic shock. He was found spontaneous spleen rupture without obvious triggers, and underwent emergency splenectomy. The pathological diagnosis of spleen was diffuse large B-cell lymphoma.
患者男，48岁，因间断发热2年就诊。患者间断发热，体温最高39 ℃，可自行热退，抗菌治疗疗效不佳，入院后无其他伴随症状及阳性体征，曾有体重明显下降，外周血乳酸脱氢酶明显增高，临床高度警惕淋巴瘤，但骨髓穿刺及活检、PET-CT未见明显异常。因患者高热，炎症指标高，铁蛋白增高，伴脾大，考虑高炎症状态，淋巴瘤待除外。给予甲泼尼龙24 mg，每天2次。患者体温正常，但出现血小板进行性下降至33×109/L。住院期间出现腹腔内出血、出血性休克，急诊手术发现患者为自发性脾破裂，行急诊脾切除术，脾脏病理诊断为弥漫性大B细胞淋巴瘤。.

BACKGROUND: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression.
METHODS: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient\'s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient\'s body temperature gradually returned to the normal range and her mood improved significantly.
CONCLUSIONS: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO.

OBJECTIVE: To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin.
METHODS: A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects, which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow.
RESULTS: The positive rates of hemophagocytes detected in the three lines decreased group, the two lines decreased group, the one line decreased group, normal group of the three lines and at least one of the three lines increased group were 86.4%, 62.1%, 38.3%, 34.6% and 33.3%, respectively. The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups ( P < 0.001). The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group, normal group of three lines and at least one of the three lines increased group ( P < 0.01). There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines (P >0.05). The missed rates of hemophagocytes in the five groups were 15.78%, 22.03%, 62.22%, 77.78% and 53.84%, respectively.
CONCLUSIONS: For patients with fever of unknown origin, especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells, which should pay attention to the detection of hemophagocytes in bone marrow. Meanwhile, if the number of three lines was normal even at least one of the three lines increased, the presence of hemophagocytes in the bone marrow slice should be also carefully observed.
UNASSIGNED: 骨髓中噬血细胞数量与外周血细胞数量的相关性分析.
UNASSIGNED: 研究不明原因发热患者骨髓中噬血细胞数量与外周血细胞数量的相关性。.
UNASSIGNED: 选取2019年1月至2021年12月本院收治的不明原因发热患者465例作为研究对象，回顾性分析其骨髓噬血细胞数量与外周血三系细胞数量的相关性。.
UNASSIGNED: 三系数量减少、两系数量减少、一系数量减少、三系数量正常以及三系正常至少一系升高组检出噬血细胞的阳性率分别为86.4%、62.1%、38.3%、34.6%及33.3%。其中三系数量减少组与其它4组相比，单位面积噬血细胞数明显升高（P < 0.001）；两系数量减少组单位面积噬血细胞数高于一系数量减少组、三系数量正常组、三系正常至少一系升高组（P <0.01）；一系数量减少组与三系数量正常组、三系正常至少一系升高组，三系数量正常组与三系正常至少一系升高组相比，单位面积噬血细胞数差异均无统计学意义（P >0.05）。5组的噬血细胞漏检率分别为15.78%、22.03%、62.22%、77.78%及53.84%。.
UNASSIGNED: 对于不明原因发热患者尤其是外周血三系及两系细胞数量明显减少者要格外注意骨髓中噬血细胞的检出，同时对于三系细胞数量正常甚至至少有一系升高者也应仔细观察髓片中是否有噬血细胞的存在。.

UNASSIGNED: Clinicians often face the challenge of differentially diagnosing febrile patients who are suspected of infectious diseases, since the clinical manifestations of infection and cancer may overlap. A single test that can detect both pathogens and tumor could provide timely and accurate diagnostic clues to aid the treatment and management of these patients.
UNASSIGNED: We enrolled eight patients to evaluate the utility of metagenomic Next-Generation Sequencing for simultaneously detecting pathogens and neoplasms using body fluids and tissue samples. Patients were selected by the following criteria: 1) Tumor was not considered upon hospitalization, but mNGS testing indicated neoplasm; 2) Tumor was not excluded, but microbial infection was primarily suspected according to initial clinical assessment.
UNASSIGNED: We detected potential pathogens in five patients, three of whom had progressed into critical infections. Moreover, abnormal chromosomal copy numbers were identified in all patients that indicated presence of neoplasms, which were pathologically confirmed.
UNASSIGNED: Although copy number variations do not render a definitive cancer diagnosis, it can prompt clinicians to conduct more focused diagnostic testing for cancer, potentially saving time and cost. As a result, integrating copy number analysis with pathogen detection in mNGS may help establish rapid and accurate diagnosis for febrile patients.

BACKGROUND: Fever of unknown origin (FUO) poses a diagnostic challenge, often requiring a systematic evaluation to uncover its elusive cause. This case study delves into the presentation of a 42-year-old Chinese male with persistent fever, muscle pain, and a perplexing rash.
METHODS: The patient\'s symptoms included a prolonged fever, chills, muscle pain, and throat discomfort, with a history of pulmonary tuberculosis. Initial diagnoses of upper respiratory infection and unspecified infection were followed by antibiotic treatments, yet the fever persisted, accompanied by an exacerbating rash.
METHODS: Extensive diagnostic investigations, including laboratory tests, imaging studies, and skin dermoscopy, provided valuable insights. The patient exhibited elevated inflammatory markers, hepatosplenomegaly, lymphadenopathy, and lung nodules. Differential diagnoses included adult-onset Still disease and drug-induced hypersensitivity syndrome.
METHODS: The patient received a series of antibiotic treatments, which initially had limited success. Upon considering an autoimmune etiology, corticosteroids were introduced, followed by cyclosporine. The patient exhibited a positive response to this immunosuppressive therapy.
RESULTS: Treatment adjustments were made, and the patient responded positively to a combination of corticosteroids and cyclosporine. His fever subsided, and laboratory markers normalized. One month after discharge, the patient showed continued improvement.
CONCLUSIONS: FUO cases often demand a multidisciplinary approach, considering rare and uncommon diseases. This case underscores the importance of thorough evaluation, collaboration between specialties, and vigilant monitoring of treatment responses. The patient\'s unique presentation emphasizes the need to consider drug-induced reactions, even when symptoms deviate from typical disease patterns, highlighting the complexities in diagnosing and managing FUO.

BACKGROUND: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT.
METHODS: This was a retrospective study conducted in a tertiary children\'s hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia.
RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia.
CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

UNASSIGNED: A 68-year-old man with intermittent fever of unknown origin for 5 months underwent 18F-FDG PET/CT to detect causative lesion. An 18F-FDG-avid lesion was revealed in the left pelvic iliac vessel region and was highly suggestive of malignancy. One and a half months later, a giant left internal iliac artery aneurysm was identified by CT angiography, corresponding to the 18F-FDG-avid lesion. Combined with elevated inflammatory markers, he was finally diagnosed as having inflammatory internal iliac artery aneurysm. An abdominal aortic aneurysm with low 18F-FDG uptake was also identified.