Abstract

Background: The etiology of fever of unknown origin (FUO) is complex and remains a major challenge for clinicians. This study aims to investigate the distribution of the etiology of classic FUO and the differences in clinical indicators in patients with different etiologies of classic FUO and to establish a machine learning (ML) model based on clinical data.Methods: The clinical data and final diagnosis results of 527 patients with classic FUO admitted to 7 medical institutions in Chongqing from January 2012 to August 2021 and who met the classic FUO diagnostic criteria were collected. Three hundred seventy-three patients with final diagnosis were divided into 4 groups according to 4 different etiological types of classical FUO, and statistical analysis was carried out to screen out the indicators with statistical differences under different etiological types. On the basis of these indicators, five kinds of ML models, i.e., random forest (RF), support vector machine (SVM), Light Gradient Boosting Machine (LightGBM), artificial neural network (ANN), and naive Bayes (NB) models, were used to evaluate all datasets using 5-fold cross-validation, and the performance of the models were evaluated using micro-F1 scores.Results: The 373 patients were divided into the infectious disease group (n = 277), non-infectious inflammatory disease group (n = 51), neoplastic disease group (n = 31), and other diseases group (n = 14) according to 4 different etiological types. Another 154 patients were classified as undetermined group because the cause of fever was still unclear at discharge. There were significant differences in gender, age, and 18 other indicators among the four groups of patients with classic FUO with different etiological types (P < 0.05). The micro-F1 score for LightGBM was 75.8%, which was higher than that for the other four ML models, and the LightGBM prediction model had the best performance.Conclusions: Infectious diseases are still the main etiological type of classic FUO. Based on 18 statistically significant clinical indicators such as gender and age, we constructed and evaluated five ML models. LightGBM model has a good effect on predicting the etiological type of classic FUO, which will play a good auxiliary decision-making function.

Highlights

  • Fever of unknown origin (FUO) is a difficult and active medical topic in the diagnosis and treatment of difficult and complicated diseases in internal medicine, and it is a challenging problem for physicians [1, 2]

  • Male patients with FUO were common in the infectious and neoplastic disease groups, whereas female patients with FUO were common in the non-infectious inflammatory disease (NIID) and other diseases groups

  • Neoplastic diseases accounted for 5.9% of classic FUO, which was significantly lower than 15%, as reported in the literature [1], which may be due to PET-CT and serum tumor markers that have been widely used in recent years [29, 30]

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Summary

Introduction

Fever of unknown origin (FUO) is a difficult and active medical topic in the diagnosis and treatment of difficult and complicated diseases in internal medicine, and it is a challenging problem for physicians [1, 2]. Because of its complex etiology, lack of characteristic clinical signs, and inadequate laboratory tests, the diagnosis is very difficult [8]. The etiological categories of classic FUO are infectious disease, non-infectious inflammatory disease (NIID), neoplastic disease, and others, and the treatment methods vary greatly, including anti-infective drugs, hormones, and chemotherapy [9,10,11]. The etiology of fever of unknown origin (FUO) is complex and remains a major challenge for clinicians. This study aims to investigate the distribution of the etiology of classic FUO and the differences in clinical indicators in patients with different etiologies of classic FUO and to establish a machine learning (ML) model based on clinical data

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