Development of anti-MDA5 autoantibody-positive dermatomyositis following the use of etanercept biosimilar in rheumatoid arthritis.

The induction of autoimmune diseases during tumor necrosis factor-alpha inhibitor (TNFi) usage has been described. Herein, we report a rare case of a 49-year-old woman with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM), which developed five weeks after the introduction of an etanercept biosimilar to rheumatoid arthritis (RA). Four of the five known cases, including ours, of anti-MDA5Ab positive DM complicated with RA revealed anti-MDA5Ab positive DM following TNFi usage. When patients with RA are diagnosed with interstitial lung disease during TNFi usage, anti-MDA5 Ab-positive DM could be a differential diagnosis.

Novel subtype of coxitis knee associated with acetabular dysplasia of the hip: a case series.

BACKGROUND: Multiple joint arthritis patterns require a comprehensive understanding to optimize patient management. This study aimed to present a patient cohort that deviated from known definitions of coxitis knee (CK), identifying and characterizing this atypical group. METHODS: Patients undergoing both total hip arthroplasty and total knee arthroplasty between January 2008 and December 2018 were retrospectively reviewed. The patients were classified into a typical coxitis knee group (classic, long leg arthropathy, and windswept deformity) and an atypical coxitis knee group. Leg-length discrepancy, body mass index (BMI), and radiographic parameters of the groups were compared and analyzed. RESULTS: A total of 31 patients were allocated to the typical coxitis knee group (n = 10), and atypical coxitis knee group (n = 21). In the atypical group, 27 hips were involved, of which 21 had acetabular dysplasia, 5 exhibited subchondral insufficiency fracture-like changes, and only 1 had classic osteoarthritis. Among the 27 knees undergoing total knee arthroplasty, 26 showed varus alignment, 1 was within the normal range, and none was valgus. Acetabular dysplasia involved ipsilateral (n = 1), contralateral (n = 14), and bilateral (n = 6) hips, showing atypical coxitis knee. Patients with acetabular dysplasia were more likely to exhibit atypical CK. CONCLUSION: Most patients in the cohort displayed acetabular dysplasia and contralateral varus knees, constituting a pattern referred to as acetabular dysplasia-associated gonarthritis. Identifying this novel subtype may have important clinical implications for regions with high risk factors, where acetabular dysplasia and constitutional genu varum are prevalent.

Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Successful management of interstitial lung disease in dermatomyositis complicated by malignancy: a case-based review.

Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM-ILD-malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM-ILD-malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM-ILD-malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature.

Aberrant DNA methylation-mediated NF-κB/fatty acid-binding protein 5 (FABP5) feed-forward loop promotes malignancy of colorectal cancer cells.

Fatty acid-binding proteins (FABPs) are intracellular lipid-binding proteins that play roles in fatty acid transport and the regulation of gene expression. Dysregulated FABP expression and/or activity have been associated with cancer pathogenesis; in particular, epidermal-type FABP (FABP5) is upregulated in many types of cancer. However, the mechanisms regulating FABP5 expression and its involvement in cancer remain largely unknown. Here, we examined the regulation of FABP5 gene expression in non-metastatic and metastatic human colorectal cancer (CRC) cells. We found that FABP5 expression was upregulated in metastatic compared with non-metastatic CRC cells as well as in human CRC tissues compared with adjacent normal tissue. Analysis of the DNA methylation status of the FABP5 promoter showed that hypomethylation correlated with the malignant potential of the CRC cell lines. Moreover, FABP5 promoter hypomethylation also correlated with the expression pattern of splice variants of the DNA methyltransferase DNMT3B. ChIP assays and luciferase reporter assays demonstrated that the transcription factor nuclear factor-kappa B (NF-κB) was involved in regulating FABP5 expression. FABP5 expression could be upregulated in metastatic CRC cells by sequential promotion of DNA demethylation followed by activation of NF-κB. We also found that upregulated FABP5 in turn controlled NF-κB activity through IL-8 production. Collectively, these findings suggest the existence of a DNA methylation-dependent NF-κB /FABP5 positive feed-forward loop that may lead to constitutive activation of NF-κB signaling pathway and play a crucial role in CRC progression.

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study.

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study. Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels. Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63-77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5-59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation. Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels.

Intensive induction therapy combining tofacitinib, rituximab and plasma exchange in severe anti-melanoma differentiation-associatedprotein-5 antibody-positive dermatomyositis.

OBJECTIVES: Anti-melanoma differentiation-associated protein-5 (MDA5) autoantibodies (Abs) are associated with rapidly progressive interstitial lung disease (RP-ILD) in dermatomyositis (DM). Because the addition of plasma exchange (PE) and rituximab (RTX) to triple therapy is inadequate in severe cases, we treat such cases with intensive induction therapy (IIT) combining all these options with tofacitinib (TOF). In this study, we investigated the poor prognostic factors and the efficacy and safety of IIT. METHODS: Thirty-three patients diagnosed with anti-MDA5 Ab-positive DM in our institution between 2014 and 2021 were included. The clinical characteristics of poor prognosis were retrospectively analysed using principal component analysis (PCA), and the outcomes of IIT were analysed in terms of survival, assessed using the Kaplan-Meier test, and adverse events. RESULTS: Although triple therapy with RTX, PE, or intravenous immunoglobulin was administered before the introduction of IIT, eight of 12 RP-ILD cases with a ferritin level >400 ng/mL (mean, 2,342) died within a median of 2.5 months. PCA revealed distinct clusters for prognosis, and age and serum ferritin were leading predictors of the prognosis. IIT, consisting of combinations of triple therapy with higher doses of methylprednisolone, PE, RTX, and TOF, was applied to eight patients (mean ferritin, 3,558). Although two patients died even with these regimens, a significant improvement in survival was documented. Several IIT-related adverse events were observed, including viral and fungal infections and cytopenia. CONCLUSIONS: IIT significantly improved the survival of patients with severe anti-MDA5 Ab-positive RP-ILD. Although infections are noted, their benefits outweigh the risks in younger patients with high serum ferritin levels.

"Coexistence of IgA nephropathy and renal artery stenosis in Takayasu arteritis: case report and literature review".

Although Takayasu arteritis (TAK) is a form of large vessel vasculitis, complications of glomerulonephritis have occasionally been observed, with mesangial proliferative glomerulonephritis as the most common. The aim of this work was to present a case-based review regarding the association of glomerulonephritis and IgA nephropathy (IgAN) with TAK. A literature search was carried out using the PubMed and Scopus databases for articles published in English, and the Ichu-shi Web for Japanese. A 34-year-old Japanese man was evaluated for proteinuria, and IgAN was diagnosed by renal biopsy. Simultaneously, aortic wall thickening and right renal artery stenosis confirmed a coexisting TAK. Prednisolone and methotrexate improved both diseases, and percutaneous transluminal renal angioplasty resulted in right renal artery reopening. Our case and literature review revealed that membranous proliferative glomerulonephritis and IgAN are common in eastern Asia, while focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis are common in other regions. The incidence of IgAN is higher in TAK cases and is mostly reported in Asia. Abdominal aortic involvement and renal artery stenosis are common in cases with preceding TAK. IgAN could be related to the cytokine network involving interleukin-6, suggesting the usefulness of tocilizumab in patients with TAK accompanied by IgAN. The type of glomerulonephritis complicated with TAK differs among regions, and patients with TAK are more likely to experience IgAN than the healthy population.

Novel Diagnostic Autoantibodies Against Endothelial Protein C Receptor in Patients With Ulcerative Colitis.

There have been many reports on serologic autoantibodies in inflammatory bowel diseases (IBD),1 consisting of ulcerative colitis (UC) and Crohn's disease (CD), and recently Kuwada et al2 reported a new autoantibody against integrin αvß6 with high sensitivity and specificity for UC. Concurrently, we had discovered autoantibodies against endothelial protein C receptor (EPCR) in Takayasu arteritis (TAK), which is sometimes complicated by UC.3 Interestingly, this autoantibody was found in most patients with TAK associated with UC, and we found that the positivity rate in patients with UC without TAK was also high, suggesting that anti-EPCR antibody is a candidate autoantibody useful for the diagnosis of UC.4 To clarify the diagnostic usefulness of anti-EPCR antibodies in patients with IBD and their relationship to several disease subphenotypes and their disease activities, we analyzed the serum samples from patients with IBD and non-IBD control subjects in Japan and the United States.

Granulomatosis with polyangiitis following Pfizer-BioNTech COVID-19 vaccination.

We report the first case of proteinase 3-antineutrophil cytoplasmic antibody-positive granulomatosis with polyangiitis (GPA) with predominant ears, nose, and throat manifestations following coronavirus disease 2019 (COVID-19) vaccination. A 63-year-old woman presented with aural fullness 3 days after vaccination. She presented with progressive rhinosinusitis and otitis media leading to profound hearing loss within 3 weeks. Clinical imaging revealed soft-tissue shadows in the paranasal sinuses with multiple pulmonary nodules, and histopathology was consistent with a diagnosis of GPA. It is crucial to be wary of the possibility of GPA in patients who received COVID-19 vaccines due to its rapid disease progression.

Myeloid immune checkpoint ILT3/LILRB4/gp49B can co-tether fibronectin with integrin on macrophages.

LILRB4 (B4, also known as ILT3/CD85k) is an immune checkpoint of myeloid lineage cells, albeit its mode of function remains obscure. Our recent identification of a common ligand for both human B4 and its murine ortholog gp49B as the fibronectin (FN) N-terminal 30 kDa domain poses the question of how B4/gp49B regulate cellular activity upon recognition of FN in the plasma and/or the extracellular matrix. Since FN in the extracellular matrix is tethered by FN-binding integrins, we hypothesized that B4/gp49B would tether FN in cooperation with integrins on the cell surface, thus they should be in close vicinity to integrins spatially. This scenario suggests a mode of function of B4/gp49B by which the FN-induced signal is regulated. The FN pull-down complex was found to contain gp49B and integrin ß 1 in bone marrow-derived macrophages. The confocal fluorescent signals of the three molecules on the intrinsically FN-tethering macrophages were correlated to each other. When FN-poor macrophages adhered to culture plates, the gp49-integrin ß 1 signal correlation increased at the focal adhesion, supporting the notion that gp49B and integrin ß 1 become spatially closer to each other there. Adherence of RAW264.7 and THP-1 cells to immobilized FN induced phosphorylation of spleen tyrosine kinase, whose level was augmented under B4/gp49B deficiency. Thus, we concluded that B4/gp49B can co-tether FN in cooperation with integrin in the cis configuration on the same cell, forming a B4/gp49B-FN-integrin triplet as a regulatory unit of a focal adhesion-dependent pro-inflammatory signal in macrophages.

Hypertrophic Pachymeningitis Development in Eosinophilic Granulomatosis with Polyangiitis at Relapse of Disease: A Case-Based Review.

Hypertrophic pachymeningitis (HP) presents with thickening of the dura mater in the cerebrum and spine, and its symptoms vary depending on the affected location. The association of HP with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recognized, and most cases are complicated by granulomatosis with polyangiitis. We report the case of a 47-year-old man who presented with HP upon relapse of eosinophilic granulomatosis with polyangiitis (EGPA), with literature review. He presented with disturbance of consciousness, and magnetic resonance imaging (MRI) revealed thickening of the dura mater around the left parietal lobe. Although myeloperoxidase (MPO)-ANCA was positive on EGPA diagnosis, the elevation of MPO-ANCA was not documented at the onset of HP. Brain perfusion scintigraphy showed an increase in blood flow in the left parietal lobe and temporal lobe, and electroencephalogram (EEG) revealed slow waves in the left parietal lobe. He was treated with a high dose of corticosteroid and rituximab, and the slow waves on EEG and brain perfusion were normalized. Although the most frequent symptom of HP is headache, disturbance of consciousness can be the manifestation of HP, and inflammation of HP could affect the cerebral parenchyma, which can be documented as abnormal EEG and perfusion scintigraphy. Literature review revealed that most of the HP in EGPA developed when EGPA relapsed, and was observed in patients with MPO-ANCA positivity. HP develops without evidence of other clinical features of EGPA; therefore, adequate imaging, including contrast-enhanced MRI, is necessary. Rituximab may be effective for treating HP complicated with EGPA.

Development of severe colitis in Takayasu arteritis treated with tocilizumab.

Relapse of Takayasu arteritis (TAK) is frequent, and the use of biologics is required in refractory cases. Tocilizumab (TCZ), a biological agent used in TAK, is known to increase the incidence of diverticulitis in patients with rheumatoid arthritis. Adverse events of TCZ in TAK have been poorly recognised. This study aimed to investigate the occurrence of severe colitis among patients with TAK receiving TCZ. We enrolled 116 patients with TAK who met the criteria of the American College of Rheumatology and visited our department between 2018 and 2020. The occurrence of severe colitis and its clinical characteristics were retrospectively evaluated. TCZ was introduced in 34 of 116 patients (29.3%). Severe colitis that required hospitalisation was observed in three of the 34 patients receiving TCZ (8.8%). All patients were female and had Numano type V artery lesions, and the ascending colon was commonly affected. Wide lesions that reached the sigmoid colon, colonic perforation, bacteraemia, or positive stool cultures were observed in some patients. All patients received antibiotics and intestinal rest, and TCZ was resumed in one patient. IL-6 plays a physiological role in the intestine, including recovery from ischaemic damage. In addition to infectious aetiology, blocking the physiological roles of IL-6 by TCZ is considered important for the development of colitis in TAK. Severe colitis is an important adverse event in patients with TAK who receive TCZ. The risk of bloodstream infection associated with colitis should be recognised, especially in patients who have undergone vascular surgery. Key Points • Severe colitis was observed in 8.8% of patients with TAK receiving tocilizumab • Patients had type V artery lesions and ascending colon involvement and were under long-term use of corticosteroids • Inhibition of the physiological roles of IL-6 in the intestinal tract might also be involved.

Predictive factors for retention of golimumab over a median 4-year duration in Japanese patients with rheumatoid arthritis in a real-world setting: A retrospective study and literature review.

OBJECTIVES: To investigate 6-year drug survival (median: 48.5 months) of golimumab and predictors for lack of efficacy leading to golimumab discontinuation in Japanese patients with rheumatoid arthritis (RA) in routine practice. METHODS: This retrospective single-center study included 60 patients with RA treated with golimumab from November 2011 to August 2020. Patients were divided into 2 groups (retention, n = 28; withdrawal due to lack of efficacy, n = 24). The retention rate was assessed using the Kaplan-Meier method, and variables associated with golimumab discontinuation were identified using the Cox proportional hazard model. RESULTS: The prevalence of concomitant methotrexate and no biologics use was significantly higher in the retention than in the withdrawal group. Overall drug survival of golimumab was 66.3%, 48.3%, and 24.5% at 12, 36, and 72 months, respectively. There were statistical differences in retention rates among groups stratified by initiation dose, methotrexate, and biologics use. Multivariate analysis revealed the factor associated with golimumab discontinuation as history of 1 (hazards ratio: 4.42, 95% CI: 1.35-19.93, P = .012) and ≥2 biologics use (7.49, 1.97-36.27, P = .003). CONCLUSIONS: Prior exposure of increasing number of biologics was identified as the most important factor negatively affecting long-term golimumab retention in Japanese patients with RA.

Multi-targeted therapy for refractory eosinophilic granulomatosis with polyangiitis characterized by intracerebral hemorrhage and cardiomyopathy: a case-based review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disorder classified under anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, predominantly affecting small- to medium-sized vessels, characterized by asthma, eosinophilia, and necrotizing granulomatous inflammation. Most patients with EGPA experience peripheral neuropathy, whereas intracerebral hemorrhage is rare as EGPA-related presentation in central nervous system involvement, causing severe morbidity and mortality. Here, we present a 45-year-old man with refractory EGPA who developed intracerebral hemorrhage as the first manifestation, followed by cardiac involvement. This patient with a history of bronchial asthma developed a right putaminal hemorrhage caused by EGPA. Although intravenous cyclophosphamide (IVCY) and mepolizumab (MPZ) induced remission, relapse was frequently observed. Subsequently, he developed cardiomyopathy despite administration of rituximab (RTX) substituted from IVCY and MPZ. Combined immunosuppressive therapy, including IVCY, MPZ, and RTX was required to inhibit vascular inflammation, leading to sustained remission. We review previously published literature while focusing on the clinical features of patients with intracerebral hemorrhage caused by EGPA and describe clinical characteristics for detecting EGPA in patients with intracerebral hemorrhage, emphasizing rapid evaluation and recognition of EGPA and adequate intervention in the early vasculitic phase of this disease. We also refer to the immunological aspects of this case. It is important to consider "multi-targeted therapy" through interleukin-5 suppression and B cell depletion in the management of refractory EGPA.

Association of various myositis-specific autoantibodies with dermatomyositis and polymyositis triggered by pregnancy.

Although pregnancy is an important risk factor for autoimmune rheumatic diseases, little is known regarding the association between pregnancy and dermatomyositis (DM) or polymyositis (PM). Herein, we present two patients with DM that developed during the perinatal period. The first patient was positive for anti-aminoacyl synthetase (ARS) antibody and developed DM in the 14th week of pregnancy. Despite treatment, her foetus died of intrauterine growth restriction in the 27th week. The second patient was positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody and developed DM 1 week after miscarriage at 9 weeks of gestation. The patient developed severe interstitial pneumonia, and intensive therapy including tofacitinib and rituximab administration was required. Our cases and a literature review revealed that various myositis-specific autoantibodies, including anti-ARS, anti-Mi-2, anti-TIF-1γ, and anti-MDA-5, are associated with DM and PM triggered by pregnancy. We also found that delay in commencing treatment in case of active disease including myositis and interstitial pneumonia, and poor response to corticosteroids were related to poor foetal outcomes in DM and PM. Although rare in pregnant women, it is critical to consider the possibility of DM and PM in patients presenting with rash, fever, weakness, and cough, and testing for myositis-specific autoantibodies is recommended.

Significant reduction of patellar height affected lower clinical outcomes and knee flexion over five-year follow-up after total knee arthroplasty.

AIMS: This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA). METHODS: We retrospectively evaluated knee radiographs of 165 knees, which underwent fixed-bearing PS-TKA with patella resurfacing. The incidence of patella baja and changes in patellar height over a minimum of five years of follow-up were determined using Insall-Salvati ratio (ISR) measurement. We examined whether patella baja (ISR < 0.8) at final follow-up affected clinical outcomes, knee joint range of motion (ROM), and Knee Society Score (KSS). We also assessed inter- and intrarater reliability of ISR measurements and focused on the relationship between patellar height reduction beyond measurement error and clinical outcomes. RESULTS: The ISR gradually decreased over five years after TKA, and finally 33 patients (20.0%) had patella baja. Patella baja at the final follow-up was not related to passive knee ROM or KSS. Interestingly, when we divided into two groups - patella baja and patella normal-alta (ISR ≥ 0.8) - the patella baja group already had a lower patellar height before surgery, compared with the patella normal-alta group. The ISR measurement error in this study was 0.17. Both passive knee flexion and KSS were significantly decreased in the group with a decrease in ISR of ≥ 0.17 at final follow-up. CONCLUSION: Patellar height gradually decreased over five years of follow-up after TKA. The reduction in patellar height beyond measurement error following TKA was associated with lower clinical outcomes. Cite this article: Bone Jt Open 2021;2(12):1075-1081.