This follow-up study explores the different clinical characteristics of patients undergoing orthopedic surgery who suffered from acute perioperative gout attacks and identifies the risk factors for gout recurrence. In the normal uric acid level group, the UA level fluctuation was greater than in the hyperuricemia group and the inflammatory reaction was stronger than in the hyperuricemia group when the acute gout attack occurred during the perioperative period. The patients in the hyperuricemia group had a higher mean acute gout recurrence rate during the follow-up period. Presenting tophi was the independent predictor of gout recurrence within the first year after orthopedic surgery. Moreover, it may be safe for a patient to have a preoperative serum UA level below 300 µmol/L.
During acute gout attacks, the serum UA levels for patients in both groups decreased to varying degrees compared with the UA level at the time of admission; the serum UA levels decreased by 42.12% in the normal uric acid group and by 22.65% in the hyperuricemia group. However, there was more fluctuation in the UA levels in the normal UA level group than in the hyperuricemia group. This study showed that blood levels of inflammatory markers (WBC and CRP levels) were higher in the normal UA group patients than in hyperuricemia group patients during the perioperative acute gout attack. Li et al. followed the UA levels in patients for 8 years and found that patients with more obvious fluctuations in UA levels demonstrated higher risks of all-cause mortality and cardiovascular disease, potentially related to the high inflammatory response induced by UA level fluctuations . However, the relationship between inflammation and UA levels is clinically controversial. Viveros-Paredes et al.  reported that inflammatory factors released into the blood circulation from tissues during acute gout attacks are positively correlated with changes in blood cortisol levels. Severe inflammatory responses stimulate cortisol secretion, thereby stimulating UA excretion. A decrease in serum UA levels can also activate the release of a series of inflammatory cytokines. Furthermore, UA level fluctuations can cause partial dissolution of preexisting tophi, activating a series of pro-inflammatory cytokines, which ultimately leads to acute gout attacks . Hyperuricemia may induce the expression of hepatic inflammatory molecules by activating the pro-inflammatory NF-κB signaling cascade . However, after multivariate analysis, serum cortisol levels in patients with essential hypertension were negatively correlated with eGFRcr-cys; however, serum cortisol levels in patients with essential hypertension were not negatively correlated with uric acid .
During the follow-up of the patients in this study, the gout recurrence rate in the hyperuricemia group was 44.7% within the first postoperative year, which was significantly higher than that in the normal UA level group. Spiga et al.  showed that persistent hyperuricemia leads to acute gout attacks by stimulating the production of inflammatory factors, such as interleukin-6 and tumor necrosis factor-α, or by inducing a systemic inflammatory response through the nuclear factor-kappa B signaling pathway. This also partly explains the high recurrence rate of gout in the hyperuricemia group 1 year after surgery in this study.
Obesity is the most important risk factor for developing gout . The potential causal relationship between obesity, serum UA levels, and gout risk is plausible , and weight loss interventions can effectively reduce gout attacks. At the population level, a large number of prospective cohort studies related to BMI have shown that lowering a patient’s BMI has an important effect on reducing the risk of gout [20, 21]. In the present study, BMI was associated with gout recurrence in the univariate analysis. However, BMI was not an independent factor influencing gout recurrence after adjusted covariables.
Tophi are the result of long-term uncontrolled uric acid. Serum urate (sUA) concentrations above the solubility limit can lead to crystal deposits . Over time, patients with gout who maintain an sUA below 6 mg/dL (360 μmol/L) can expect to remain gout-free [23, 24], but higher sUA levels can cause gout stone formation and an increased risk of gout recurrence [25, 26]. The formation of gout stones is evidence of poor control of uric acid levels over a long period of time, and elevated uric acid levels are a major risk factor for gout attacks ; therefore, gout stone formation indirectly causes an increased risk of recurrent gout in patients. Consistent with previous studies, the present results of this study showed that Tophi was an independent risk factor for gout recurrence within 1 year.
In our study, all patients experienced some degree of joint swelling and pain, and 34.4% (22/68) of patients had a fever. After treatment measures, including the administration of NSAIDs, drinking > 2000 mL/day of water, and glucocorticoid administration (metoprolol 4 mg), the symptoms were relieved after 4–5 days. However, when the gout attack site is the surgical site, especially in a joint that has been replaced [28, 29], the most important differential diagnosis is periprosthetic infection. Both diseases can manifest as joint redness, swelling, heat, pain, dysfunction, and the presence of elevated inflammatory marker levels. The main indicators of gout are (1) medical history, focusing on previous gout attacks; (2) detailed physical examinations to determine whether there is pain in other parts of the body, such as joints that are prone to gout (first metatarsophalangeal joint and metacarpophalangeal joint); (3) accurate tests (e.g., local musculoskeletal ultrasound, dual-energy computed tomography, joint cavity punctures, joint fluid leukocyte counts, classification, bacterial cultures, and urate crystal observations); and (4) the results of attempts to diagnose and treat (if the symptoms are significantly relieved following the administration of NSAIDs, colchicine, or other drugs, a diagnosis of gout is likely).
Antibiotics are not recommended as a treatment course until a definitive diagnosis is made, as they can affect the overall management of periprosthetic infections. An involved joint may demonstrate both gout and infection. Although rare and mostly reported in individual cases , a previous study  reported 30 cases of infected joints, wherein the local deposition of urate crystals was observed while culturing the pathogenic bacteria. Therefore, detailed medical history inquiries and careful physical and related examinations can reduce misdiagnoses.
This study has some limitations. First, the serum UA measurements during the perioperative period were not made under standard conditions. In clinical workups, blood can generally be drawn from patients on an empty stomach, without special concerns about whether the patient has had a high-purine diet. The diet has a certain degree of influence, resulting in index deviation. Second, normal patients under stress conditions, such as trauma and surgery, exhibit inflammatory markers (WBC, CRP, ESR, and others) that peak within 24–72 h after the stress incident. At this time, the measured inflammatory indicators may not accurately reflect the acute gout attack. The results of this study need to be verified in future studies with larger sample sizes.