Analysis of the therapeutic effect and side effects of drug treatment for granulomatous lobular mastitis

Analysis of the therapeutic effect and side effects of drug treatment for granulomatous lobular mastitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analysis of the therapeutic effect and side effects of drug treatment for granulomatous lobular mastitis Boyu Shang, Tianyi Zhang, Chang Liu, Zonglin Yuan, Yao Wang, Jing Feng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6759384/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objectives: To explore the risk factors that are associated to the recurrence of granulomatous lobular mastitis (GLM) after treatment and to develop a nomogram model that can predict the risk of recurrence. Methods: Medical records and follow-up data from GLM patients treated at our facility were retrospectively analyzed. In order to identify independent risk factors for GLM recurrence, the patients were split into groups with and without recurrence using univariate and multivariate logistic regression analyses. A predictive nomogram model was built using these variables, and its performance was evaluated by plotting the calibration curve, receiver operating characteristic (ROC), area under the curve (AUC), and decision curve analysis (DCA) curves. Results: We evaluated the data of 287 GLM patients, of which 36 patients (12.5%) experienced recurrence, while the remaining 251 patients (87.5%) were included in the non-recurrence group. The affected side's nipple discharge was detected using multivariate logistic regression, nipple inversion on the affected side, surgical treatment, and younger age as the independent risk factors for recurrence ( P < 0.05). The model had an AUC of 0.805 (95% CI: 0.737–0.872), 81.7% sensitivity, and 66.7% specificity. The calibration curve was consistent with the ideal curve, and the DCA indicated good clinical utility of the model. Conclusion: Independent risk factors for GLM recurrence include younger age, surgical treatment, nipple discharge on the affected side, and nipple inversion on the affected side. The nomogram based on these factors demonstrated good predictive value for GLM recurrence. Granulomatous lobular mastitis Recurrence risk factors Prediction model ROC curve Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Women in their reproductive years are frequently affected by granulomatous lobular mastitis (GLM), a rare benign breast inflammatory disease. Though the exact cause is not fully understood, possible contributors include infection, autoimmunity, and hormonal imbalances. 1 However, the clinical and imaging presentations of GLM are variable and non-specific, and no standard treatment protocol has been devised so far. Standard treatment approaches for GLM involve surgical procedures, corticosteroid administration, anti-tuberculosis therapy, the use of immunosuppressive drugs, traditional Chinese medicine, and conservative management through observation. The options for surgical treatment are incision and drainage of the abscess, quadrant resection, subcutaneous gland excision, and total mastectomy combined with I/II-stage breast prosthesis or autologous tissue reconstruction. 2 , 3 However, surgery may damage the appearance and shape of the affected breast, causing significant physiological and psychological trauma to the patients. Thus, the primary challenge of surgical intervention is maintaining a balance between therapeutic efficacy and postoperative esthetic outcomes. On the other hand, long-term treatment with corticosteroids can lead to weight gain and Cushing’s syndrome 4 . At the same time, immunosuppressants like methotrexate may cause serious adverse reactions, such as bone marrow suppression, interstitial pneumonia, and folate deficiency. 5 Following Taylor et al.'s initial discovery of Corynebacteria in GLM lesions in 2003, various research groups have verified the presence of Corynebacteria in GLM-affected areas. 6 , 7 Accordingly, the triple anti-tuberculosis regimen consisting of rifampicin, isoniazid, and ethambutol has emerged as a novel treatment option for GLM, and the results have been promising. 8 , 9 The lipid-rich cell wall of Corynebacteria renders it susceptible to the lipophilic antibiotic rifampicin, which may underlie the effectiveness of the triple anti-tuberculosis regimen. 9 In individuals with refractory and severe GLM, previous studies have demonstrated that surgical intervention in combination with corticosteroid treatment can reduce recurrence rates. 10 , 11 These reports led us to treat certain GLM patients at our centre with a triple anti-tuberculosis drug regimen in addition to surgery. The current study's objectives were to construct a nomogram model for predicting recurrence risk and identify risk factors for GLM recurrence by examining clinical data from a large cohort. Materials and Methods Participants The First Affiliated Hospital of Harbin Medical University's Department of Breast Surgery gathered and examined follow-up, treatment, demographic, and clinical data for 316 GLM patients who were clinically cured between January 2019 and June 2023. The patients were grouped according to whether or not they had experienced a recurrence. The following inclusion criteria were: (1) GLM was confirmed histopathologically; (2) liver and kidney function were normal. The following were the exclusion criteria: (1) pregnant or nursing women; (2) those with rifampicin, isoniazid, or ethambutol allergies; (3) the existence of cancerous breast tumors; (4) serious underlying medical conditions; and (5) refusal to take part in the study. The full eradication of breast lesions following treatment, as confirmed by imaging and clinical examinations, was defined as the disease cure. The term "recurrence" was defined as the recurrence of redness, swelling, pain, or any other symptom in the same location of the affected breast after a clinical cure or the appearance of a new lesion on ultrasound that was confirmed as GLM on pathological examination. This study was approved by the First Affiliated Hospital's Ethics Committee at Harbin Medical University (No. 2024182). Treatment The patients opted surgery, triple anti-tuberculosis drugs, or combination treatment, depending on the severity of the disease, the size of the GLM mass, the GLM mass ratio to breast tissue, and their own preferences. 1) Surgical treatment: Both the inflamed breast tissue and some of the normal tissue around it were removed entirely. Additionally, any damaged skin was removed. In addition, if the lesion invaded the main milk duct, the nipple-areola duct system was also excised. Hydrogen peroxide, iodine solution, and saline were used to repeatedly irrigate the wound during the procedure. After that, the incision was closed, and a negative pressure drainage tube was inserted. If postoperative incisions showed evidence of inflammatory infiltration or purulence, they were not immediately sutured. Instead, wounds were managed with open care until local inflammation subsided, followed by secondary suturing. 2) Triple anti-tuberculosis drug therapy: All patients received a standard anti-tubercular regimen consisting of oral rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day). The course of treatment lasted between 6 and 9 months, and it was terminated when the sonographic results and clinical symptoms had subsided for more than one month. Monthly liver function tests were conducted during the treatment to monitor for adverse reactions. Patients who developed abscesses during treatment underwent incision and drainage or ultrasound-guided aspiration. 3) Combination treatment: Patients initially underwent surgical intervention as previously described, followed by 1 to 3 months, oral triple anti tuberculosis therapy. The duration of pharmacologic treatment was determined by the severity of the preoperative disease and the postoperative wound healing status. Liver function tests were conducted monthly during the treatment period. Observation indicators Information regarding demographics, clinical presentation, and treatment outcomes was retrospectively gathered through a review of medical records, outpatient follow-up assessments, and structured telephone interviews. All patients were followed up until July 2024. The observation indicators included age, past medical history, and body mass index (BMI), including reproductive, obstetric, and breastfeeding history, recent breast trauma history, smoking history, lactational mastitis history, autoimmune disease history, and exposure to or history of tuberculosis, history of psychiatric disorders, history of oral contraceptive use, diameter of the target lesion, affected side, location of the lesion, menopause, the affected side's nipple discharge, the affected side's nipple inversion, treatment method, local manifestations, and systemic manifestations. Statistical analysis SPSS version 27.0 was used for the statistical analysis. Fisher's exact or Pearson's chi-squared test were used for intergroup comparisons, while numbers and percentages were used to present categorical data. Groups were compared using the independent two-sample t-test or Mann-Whitney U test, and continuous data was presented as median (range) or mean ± standard deviation (mean ± SD). The normality of the data distribution was evaluated using the Kolmogorov–Smirnov test. Multivariate analysis was conducted through logistic regression. A risk prediction nomogram was constructed using the rms package in R Studio version 4.2.2. Bootstrap resampling (1,000 iterations) was performed for internal validation. ROC curves, calibration plots, and decision curve analysis were used to assess the model's clinical utility and predictive performance. P value < 0.05 qualified as statistically significant. Results Clinical data of patients From January 2019 to June 2023, 316 patients who were cured of GLM were enrolled in the study. Of the initial study population, 29 patients were lost to follow-up, resulting in a final cohort of 287 patients for analysis. From 13.27 to 67.9 months, the median follow-up was 35.63 months. Recurrence accounted for 36 patients (12.5%) and non-recurrence for 251 (87.5%). Among the study population, six patients presented with psychiatric comorbidities. A history of tuberculosis or documented exposure was noted in three patients. Autoimmune conditions were reported in six patients, of whom five had rheumatic diseases, and one had ankylosing spondylitis. Surgical treatment was given to 102 patients, triple anti-tuberculosis drug therapy to 100, and combined treatment to 85. No severe adverse reactions were observed during the treatment process. Identification of risk factors for GLM recurrence In the univariate regression analysis, factors significantly linked to GLM recurrence (P < 0.05) included nipple discharge on the affected side (1 = yes, 0 = no), nipple inversion on the affected side (1 = yes, 0 = no), treatment approach (1 = surgical treatment, 2 = triple anti-tuberculosis drug therapy, 3 = combined treatment), and age. There were no differences between the recurrence and non-recurrence groups for the other variables (P > 0.05). (Tabel 1). The multivariate logistic regression analysis includes the factors that showed statistical significance in the univariate analysis. Table 2 presents the multivariate analysis results, indicating that nipple discharge, nipple inversion (both on the affected side), surgical intervention, and younger patient age were significantly associated with an increased risk of GLM recurrence (P < 0.05). Establishment of a risk prediction model for GLM recurrence Using the independent risk factors identified through multivariate analysis, a predictive nomogram was constructed to estimate the risk of GLM recurrence in individual patients (Fig. 1). The calibration curve and the ideal reference line showed strong concordance when the model was internally validated using bootstrap resampling. The Hosmer–Lemeshow goodness-of-fit test yielded no statistical significance ( P > 0.05), indicating adequate model calibration (Fig. 2). The area under the ROC curve for GLM recurrence was 0.805 (95% CI: 0.737–0.872), with a cutoff value of 0.171, sensitivity of 81.7%, and specificity of 66.7%, indicating good discrimination ability of the model (Fig. 3). The decision curve analysis (DCA) indicated that the nomogram provides a net clinical benefit across a range of threshold probabilities, supporting its potential utility in clinical decision-making (Fig. 4). Discussion The mechanisms underlying GLM recurrence are currently unclear, and little is known regarding the risk factors. Consistent with this, no standardized approach has been established for managing recurrent GLM. Since 2019, our center has implemented a treatment protocol combining surgical intervention with a triple anti-tuberculosis drug regimen for patients diagnosed with GLM. Using a single-center patient cohort, we looked at the risk factors for GLM recurrence in this study to identify patients who were at high risk of relapsing after being cured and to develop early intervention and prevention strategies. Nipple inversion refers to the inability of the nipple to protrude normally beyond the plane of the areola, resulting in inward retraction. It can impair duct morphology and prevent the expulsion of breast tissue secretions and metabolic products from the ducts, resulting in blockage of the milk ducts. The metabolic byproducts invade the duct walls and leak into the interstitial tissue of the lobules, eventually triggering T-cell-mediated immune responses and granuloma formation, which result in chronic sterile inflammation. 12 Additionally, nipple inversion makes it difficult to maintain local hygiene, allowing oils, dirt, and secretions to collect and serve as a favorable medium for bacterial growth, which can easily lead to infections. Hua et al. 13 identified nipple inversion as an independent risk factor for GLM recurrence. Additionally, our study found that patients with nipple inversion had a 2.357-fold increased risk of GLM recurrence compared to those without. Even after clinical cure, inversion-induced ductal obstruction increased the risk of recurrence or the development of new lesions. Therefore, nipple inversion traction should be performed during the surgical intervention for GLM to minimize the risk of postoperative recurrence. Nipple discharge can increase the risk of retrograde bacterial infection by exposing the milk ducts to the external environment. In our study, 16.4% of the patients (47 out of 287) showed nipple discharge. Yuan et al. considered bacterial infection as a possible etiological factor for GLM. 2 In addition, Tian et al. 14 reported that patients with purulent nipple discharge had a 3.356-fold higher risk of GLM recurrence compared to those with normal nipples. Although we did not detect any association between BMI and GLM recurrence, Huang et al. 15 suggested that obese or overweight women may be at a higher risk of GLM recurrence. This is not surprising given that the adipose tissue plays a crucial role in endocrine function, and adipokines influence local estrogen receptors. An increase in adipokines may lead to elevated estrogen levels in the breast tissue, thereby promoting secretion and dilation of the milk ducts and triggering local inflammatory responses. 16 , 17 Furthermore, several studies 18 , 19 have suggested a potential association between hyperprolactinemia and the development of GLM. Therefore, it is essential to closely monitor prolactin levels in patients with nipple discharge. In addition, hyperprolactinemia can be managed with drugs such as bromocriptine. For patients with nipple discharge, if the diseased tissue invades the main duct during surgery, the ductal system behind the areola should be excised simultaneously to reduce the risk of recurrence. Despite the availability of various treatment options for GLM, a universally accepted standardized treatment protocol has yet to be established. Previous studies 14 , 20 have indicated a correlation between treatment methods and GLM recurrence, which is also consistent with our findings. Surgical intervention was associated with the highest recurrence risk among the three treatment methods discussed herein. Surgical treatment is currently the most widely adopted approach, providing rapid symptom relief. The chance of recurrence following surgery can be as high as 50%, 21, 22 , most likely because it is difficult to accurately delineate the lesions visually during surgery. Asoglu et al. 23 reported that complete excision of GLM lesions could significantly reduce postoperative recurrence rates. For lesions occupying a large volume of breast tissue, extensive excision is often necessary to ensure treatment efficacy and prevent recurrence, which, however, can significantly affect breast appearance and cause substantial physical and psychological trauma to the patient. 24 The occurrence of GLM is associated with Corynebacteria , particularly C. kroppenstedtii . 6 , 25 , 26 Co et al. 27 successfully isolated C. kroppenstedtii from the lesions of patients with recurrent GLM and identified it as an independent risk factor for recurrence. Although we did not compare the status of Corynebacteria between the patient groups, triple anti-tuberculosis therapy with or without surgical intervention lowered the risk of recurrence, which can be attributed to the anti-bacterial effects of the drugs. Interestingly, we found no discernible difference between patients receiving combination therapy and those receiving anti-tuberculosis drugs alone. This may be due to the longer duration of the drug therapy alone (6–9 months) compared to that of the combined treatment (1–3 months). Zhou et al. 9 also reported that triple anti-tuberculosis therapy resulted in a 78.51% cure rate for GLM, with a recurrence rate of under 10%. Therefore, choosing the appropriate treatment plan is crucial for preventing GLM recurrence. For patients undergoing surgery to achieve prompt symptom relief, a postoperative regimen of sequential triple anti-tuberculosis therapy could prove effective. The impact of age on GLM recurrence has been analyzed in numerous studies. Consistent with our findings, Li et al. 28 identified age as a risk factor for GLM recurrence that is independent and found that younger patients had a relatively higher risk of relapse. While the reason for increased recurrence in younger GLM patients remains uncertain, Huang et al. 15 observed that an elevated follicle-stimulating hormone (FSH) to luteinizing hormone (LH) ratio was associated with a higher probability of recurrence. Younger patients may experience perturbations in sex hormones such as FSH and LH due to more active ovarian function, which in turn can affect the breast. Therefore, greater attention should be given to younger patients with GLM. Previous studies 20 , 27 , 29 have shown that lesion size, location, quadrant of the lesion, presence of abscesses, ulceration, sinus formation, and local inflammation are not risk factors for GLM recurrence, which aligns with our study's results. Although we did not observe any association between GLM recurrence and oral contraceptive use or smoking, Tasci et al. 30 found that oral contraceptive use was more common in the group experiencing recurrence compared to the group without recurrence. In addition, Co et al. 27 identified smoking as an independent risk factor for GLM recurrence. Such inconsistencies may be due to the small sample size of the present study and will have to be addressed in future research with a larger sample size. We developed a nomogram model to predict GLM recurrence based on four independent risk factors: age, treatment method, nipple discharge on the affected side, and nipple inversion on the affected side. The model showed high discriminatory ability and clinical applicability, and the calibration curve closely aligned with the ideal curve, demonstrating a good fit between the predicted and actual outcomes. Limitations This study had a few limitations that ought to be considered. Due to the study's retrospective design and its single-center setting, we could not gather data from patients who were lost to follow-up. In addition, we did not identify Corynebacteria in the patient samples through culture. Moreover, the nomogram model only underwent internal validation and must be validated in an external cohort to improve its accuracy. Hence, future studies should prioritize multicenter, large-scale prospective randomized controlled trials to offer fresh insights into preventing GLM recurrence. Conclusions The independent risk factors for GLM recurrence are younger age, surgical treatment, nipple discharge on the affected side, and nipple inversion on the affected side. Appropriate treatment methods should be employed for GLM management, with a particular focus on correcting nipple inversion and eliminating nipple discharge. In addition, younger patients should be considered at high risk for recurrence. The nomogram model, developed using the aforementioned factors, exhibited strong accuracy and could assist in early detection of high-risk groups for GLM recurrence, enabling prompt intervention to lower recurrence risk. Abbreviations GLM Granulomatous lobular mastitis ROC Receiver operating characteristic AUC Area under the curve DCA Decision curve analysis BMI Body mass index FSH Follicle-stimulating hormone LH Luteinizing hormone Declarations Acknowledgements Not applicable. Authors' contributions Boyu Shang, Jing Feng, and Yi Zhou conceptualized and oversaw the study. Boyu Shang, Tianyi Zhang, Chang Liu, Zonglin Yuan, and Yao Wang handled data collection and organization. Jing Feng and Boyu Shang conducted statistical analysis and data interpretation. Boyu Shang wrote the initial manuscript, with revisions for key content provided by Yi Zhou and Jing Feng. Funding This research was funded by the Natural Science Foundation of Heilongjiang Province of China (YQ2020H012), the Research and Innovation Fund of the First Affiliated Hospital of Harbin Medical University (2020B12), the China Postdoctoral Science Foundation (2020M670927), and the Heilongjiang Province Postdoctoral Fund (LBH-Z19171). Ethics approval and informed consent The study was approved by the Ethics Board of the First Affiliated Hospital of Harbin Medical University (Reference No. 2024182) and complied with the Declaration of Helsinki guidelines. It was logged with the US Clinical Trial Registry (ID: NCT06565845) on August 21, 2024. Written informed consent was secured from all participants, with parental or legal guardian consent obtained for individuals under 16 years old. Competing interests The authors confirm they have no financial conflicts or personal relationships that might have influenced the conduct or results of this study. References Tan Q, Tay S, Gudi M, Nadkarni N, Lim S, Chuwa E. Granulomatous Mastitis and Factors Associated with Recurrence: An 11-Year Single-Centre Study of 113 Patients in Singapore. World journal of surgery. 2019;43(7):1737-45. Yuan Q-Q, Xiao S-Y, Farouk O, Du Y-T, Sheybani F, Tan QT, et al. 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Journal of inflammation research. 2022;15:5401-12. Tasci H, Turk E, Erinanc O, Erkan S, Gundogdu R, Karagulle E. Factors Affecting Recurrence of Idiopathic Granulomatous Mastitis. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2022;32(2):161-5. Tables Table 1. Results of univariate analysis of risk factors for GLM. Variables Recurrence ( n = 36) No recurrence ( n = 251) Test statistic P -value Age (years), (mean ± SD) 30.035±6.553 33.885±7.59 -2.796 0.005 BMI (kg/m 2 ), (mean ± SD) 24.585±5.17 25.625±4.73 -1.602 0.109 Number of pregnancies ( n ), (mean ± SD) 1.835±1.44 1.655±0.95 -0.28 0.779 Number of births ( n ), (mean ± SD) 1.085±0.60 1.175±0.48 -0.822 0.411 Diameter of the target lesion (cm), (mean ± SD) 5.135±2.38 5.365±2.65 -0.307 0.759 Follow-up time (months), median (range) 40.02 (14.96,67.83) 35.20(13.27,67.90) -1.486 0.137 Lactation n (%) 3.243 0.072 Yes 27(75.0) 217(86.5) No 9(25.0) 34(13.5) Nipple discharge on the affected side n (%) 8.267 0.004 Yes 27(75.0) 20(8.0) No 9(25.0） 231(92.0) Nipple inversion on the affected side n (%) 7.699 0.006 Yes 23(63.9) 99(39.4) No 13(36.1) 152(60.6) Reproductive history n (%) 3.155 0.076 # Yes 32(88.9） 243(96.8) No 4(11.1) 8(3.2) Recent history of breast trauma n (%) 1.213 0.271 Yes 17(47.2) 143(57) No 19(52.8) 108(43) Smoking n (%) 0.100 0.752 # Yes 2(5.6) 11(4.4) No 34(94.4) 240(95.6) History of mastitis during lactation n (%) 0.013 0.911 # Yes 1(2.8) 12(4.8) No 35(97.2) 239(95.2) History of autoimmune disease n (%) 4.623 0.139 # Yes 1(2.8) 5(2.0) No 35(97.2) 246(98.0) History of tuberculosis and exposure to tuberculosis n (%) >0.99 # Yes 0 3(1.2) No 36(100.0) 248(98.8) Mental disorders n (%) >0.99 # Yes 0 6(2.4) No 36(100.0) 245(97.6) Oral Contraceptive pills n (%) >0.99 # Yes 0 5(2.0) No 36(100.0) 246(98.0) Menopause n (%) 0.537 0.463 # Yes 0 10(4.0) No 36(100.0) 241(96.0) Side n (%) 1.809 0.405 Left 20(55.6) 118(47.0) Right 16(44.4) 125(49.8) Bilateral 0 8(3.2) Lesion location n (%) 2.413 0.801 # Upper outer quadrant 10(27.8) 55(21.9) Lower outer quadrant 3(8.3) 26(10.4) Upper inner quadrant 7(19.4) 50(19.9) Lower inner quadrant 3(8.3) 25(10.0) Multiple quadrants 8(22.2) 74(29.5) Retroareolar 5(13.9) 21(8.4) Therapeutic modality n (%) 18.635 0.999 # Yes 36(100.0) 247(98.4) No 0 4(1.6) Pain n (%) 1.123 0.289 Yes 27(75.0) 166(66.1) No 9(25.0) 85(33.9) Abscess n (%) 1.545 0.214 Yes 16(44.4) 85(33.9) No 20(55.6) 166(66.1) Ulceration n (%) 0.075 0.785 Yes 12(33.3) 78(31.1) No 24(66.7) 173(68.9) Tenderness n (%) 0.186 0.666 Yes 31(86.1) 209(83.3) No 5(13.9) 42(16.7) Sinus formation n (%) 0.368 0.544 # Yes 3(8.3) 34(13.5) No 33(91.7) 217(86.5) Inflammatory hyperemic skin n (%) 0.369 0.543 Yes 23(63.9) 147(58.6) No 13(36.1) 104(41.4) Edema n (%) 1.444 0.229 Yes 25(69.4) 148(59.0) No 11(30.6) 103(41.0) Systemic symptoms Arthralgia n (%) 1.327 0.249 # Yes 1(2.8) 26(10.4) No 35(97.2) 225(89.6) Erythema nodosum n (%) 0.999 # Yes 2(5.6) 15(6.0) No 34(94.4) 236(94.0) Fever n (%) 0.999 # Yes 3(8.3) 23(9.2) No 33(91.7) 228(90.8) # Fisher’s exact test Table 2. Results of multivariate logistic analysis of risk factors for GLM. Variables β SE Wald OR (95%CI) P-value Nipple discharge on the affected side 1.720 0.548 9.856 5.584 (1.908–16.341) 0.002 Nipple inversion on the affected side 1.027 0.408 6.320 2.792 (1.254–6.216） 0.012 Therapeutic modality Surgical treatment —— —— Reference —— —— Triple anti-tuberculosis drug therapy -2.209 0.585 14.246 0.110 (0.035–0.346) <0.001 Combination therapy -1.577 0.503 9.816 0.207 (0.077–0.554) 0.002 Age -0.096 0.030 10.295 0.908 (0.856–0.963） 0.001 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Jun, 2025 Reviews received at journal 23 Jun, 2025 Reviews received at journal 15 Jun, 2025 Reviewers agreed at journal 13 Jun, 2025 Reviewers agreed at journal 12 Jun, 2025 Reviewers invited by journal 12 Jun, 2025 Editor assigned by journal 28 May, 2025 Submission checks completed at journal 28 May, 2025 First submitted to journal 27 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6759384","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471608989,"identity":"01282472-206a-4056-9aca-e667acb43656","order_by":0,"name":"Boyu Shang","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Boyu","middleName":"","lastName":"Shang","suffix":""},{"id":471608990,"identity":"92b05823-9a35-481a-a48a-dd0ad0c838ab","order_by":1,"name":"Tianyi Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tianyi","middleName":"","lastName":"Zhang","suffix":""},{"id":471608991,"identity":"7327dfbd-3252-44b7-9cab-0f0ebeb95427","order_by":2,"name":"Chang Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chang","middleName":"","lastName":"Liu","suffix":""},{"id":471608992,"identity":"ec9baa91-c97b-422e-9ec8-62d42924de6f","order_by":3,"name":"Zonglin Yuan","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zonglin","middleName":"","lastName":"Yuan","suffix":""},{"id":471608993,"identity":"1d03bd88-f512-40fc-9c7b-4c14dbd5d41a","order_by":4,"name":"Yao Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Wang","suffix":""},{"id":471608994,"identity":"990eb1d2-ce61-49b3-b922-1c8fddce790a","order_by":5,"name":"Jing Feng","email":"","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Feng","suffix":""},{"id":471608995,"identity":"115f2656-6521-4ae2-b334-eee0edb99dff","order_by":6,"name":"Yi Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACPgYeBoMPBhI8/MzMhx8QpYUNqMVwRoWNjGQ7W5oB0VqYec6k2Ric51GQIE6LRO6BAt62wzzGh4EuZKixiSZCS16CgSRQi9lh3gMPGI6l5TYQ1pJjYGAI1sKXYMDYcJhILYkghzXzGEgQr+XAmTQeA2aitfC8SzBsqLDhkTgMDOQEYvzCz557zPiPgYQ9f//hww8+1NgQ1gKyCBGDCUQoBwHmB0QqHAWjYBSMgpEKAKlIODB6ZhDjAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Harbin Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yi","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2025-05-27 12:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6759384/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6759384/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84780755,"identity":"67db6944-6fdc-4fe2-9c7c-d58c0efa11dc","added_by":"auto","created_at":"2025-06-17 09:27:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50850,"visible":true,"origin":"","legend":"\u003cp\u003eClinical model (nomogram) for predicting the risk of GLM.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6759384/v1/6c837ff928795b67b1448970.png"},{"id":84782304,"identity":"c7efc306-4662-4edf-86b2-dc551745cb6e","added_by":"auto","created_at":"2025-06-17 09:43:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":66244,"visible":true,"origin":"","legend":"\u003cp\u003eCalibration curves of the prediction model\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6759384/v1/250fa17b695a92bc2c5dcab9.png"},{"id":84781373,"identity":"5940e7c0-eaa6-4844-b80e-7e57d8b98074","added_by":"auto","created_at":"2025-06-17 09:35:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":77421,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic curve of the prediction model\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6759384/v1/e84f6e0f18e42bb70b483052.png"},{"id":84780751,"identity":"37c1f067-724f-4ac7-9517-6fa8021794cc","added_by":"auto","created_at":"2025-06-17 09:27:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":89372,"visible":true,"origin":"","legend":"\u003cp\u003eDecision curve analysis (DCA) of the prediction model\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6759384/v1/df76594ebb376c8aec780fc3.png"},{"id":84782770,"identity":"18a1c44f-08ca-4c36-94e5-8c7927fc2435","added_by":"auto","created_at":"2025-06-17 09:51:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1218830,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6759384/v1/0ad88b69-3d88-4ac9-9219-3a20789a7bb0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of the therapeutic effect and side effects of drug treatment for granulomatous lobular mastitis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWomen in their reproductive years are frequently affected by granulomatous lobular mastitis (GLM), a rare benign breast inflammatory disease. Though the exact cause is not fully understood, possible contributors include infection, autoimmunity, and hormonal imbalances.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e However, the clinical and imaging presentations of GLM are variable and non-specific, and no standard treatment protocol has been devised so far. Standard treatment approaches for GLM involve surgical procedures, corticosteroid administration, anti-tuberculosis therapy, the use of immunosuppressive drugs, traditional Chinese medicine, and conservative management through observation. The options for surgical treatment are incision and drainage of the abscess, quadrant resection, subcutaneous gland excision, and total mastectomy combined with I/II-stage breast prosthesis or autologous tissue reconstruction.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e However, surgery may damage the appearance and shape of the affected breast, causing significant physiological and psychological trauma to the patients. Thus, the primary challenge of surgical intervention is maintaining a balance between therapeutic efficacy and postoperative esthetic outcomes. On the other hand, long-term treatment with corticosteroids can lead to weight gain and Cushing\u0026rsquo;s syndrome\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. At the same time, immunosuppressants like methotrexate may cause serious adverse reactions, such as bone marrow suppression, interstitial pneumonia, and folate deficiency.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Following Taylor et al.'s initial discovery of \u003cem\u003eCorynebacteria\u003c/em\u003e in GLM lesions in 2003, various research groups have verified the presence of \u003cem\u003eCorynebacteria\u003c/em\u003e in GLM-affected areas.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Accordingly, the triple anti-tuberculosis regimen consisting of rifampicin, isoniazid, and ethambutol has emerged as a novel treatment option for GLM, and the results have been promising.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e The lipid-rich cell wall of \u003cem\u003eCorynebacteria\u003c/em\u003e renders it susceptible to the lipophilic antibiotic rifampicin, which may underlie the effectiveness of the triple anti-tuberculosis regimen.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In individuals with refractory and severe GLM, previous studies have demonstrated that surgical intervention in combination with corticosteroid treatment can reduce recurrence rates.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e These reports led us to treat certain GLM patients at our centre with a triple anti-tuberculosis drug regimen in addition to surgery. The current study's objectives were to construct a nomogram model for predicting recurrence risk and identify risk factors for GLM recurrence by examining clinical data from a large cohort.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe First Affiliated Hospital of Harbin Medical University\u0026apos;s Department of Breast Surgery gathered and examined follow-up, treatment, demographic, and clinical data for 316 GLM patients who were clinically cured between January 2019 and June 2023. The patients were grouped according to whether or not they had experienced a recurrence. The following inclusion criteria were: (1) GLM was confirmed histopathologically; (2) liver and kidney function were normal. The following were the exclusion criteria: (1) pregnant or nursing women; (2) those with rifampicin, isoniazid, or ethambutol allergies; (3) the existence of cancerous breast tumors; (4) serious underlying medical conditions; and (5) refusal to take part in the study. The full eradication of breast lesions following treatment, as confirmed by imaging and clinical examinations, was defined as the disease cure. The term \u0026quot;recurrence\u0026quot; was defined as the recurrence of redness, swelling, pain, or any other symptom in the same location of the affected breast after a clinical cure or the appearance of a new lesion on ultrasound that was confirmed as GLM on pathological examination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was approved by the First Affiliated Hospital\u0026apos;s Ethics Committee at Harbin Medical University (No. 2024182).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients opted surgery, triple anti-tuberculosis drugs, or combination treatment, depending on the severity of the disease, the size of the GLM mass, the GLM mass ratio to breast tissue, and their own preferences.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1) Surgical treatment:\u003c/strong\u003e Both the inflamed breast tissue and some of the normal tissue around it were removed entirely. Additionally, any damaged skin was removed. In addition, if the lesion invaded the main milk duct, the nipple-areola duct system was also excised. Hydrogen peroxide, iodine solution, and saline were used to repeatedly irrigate the wound during the procedure. After that, the incision was closed, and a negative pressure drainage tube was inserted. If postoperative incisions showed evidence of inflammatory infiltration or purulence, they were not immediately sutured. Instead, wounds were managed with open care until local inflammation subsided, followed by secondary suturing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2) Triple anti-tuberculosis drug therapy:\u003c/strong\u003e All patients received a standard anti-tubercular regimen consisting of oral rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day). The course of treatment lasted between 6 and 9 months, and it was terminated when the sonographic results and clinical symptoms had subsided for more than one month. Monthly liver function tests were conducted during the treatment to monitor for adverse reactions. Patients who developed abscesses during treatment underwent incision and drainage or ultrasound-guided aspiration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3) Combination treatment:\u003c/strong\u003e Patients initially underwent surgical intervention as previously described, followed by 1 to 3 months, oral triple anti tuberculosis therapy. The duration of pharmacologic treatment was determined by the severity of the preoperative disease and the postoperative wound healing status. Liver function tests were conducted monthly during the treatment period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObservation indicators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformation regarding demographics, clinical presentation, and treatment outcomes was retrospectively gathered through a review of medical records, outpatient follow-up assessments, and structured telephone interviews. All patients were followed up until July 2024. The observation indicators included age, past medical history, and body mass index (BMI), including reproductive, obstetric, and breastfeeding history, recent breast trauma history, smoking history, lactational mastitis history, autoimmune disease history, and exposure to or history of tuberculosis, history of psychiatric disorders, history of oral contraceptive use, diameter of the target lesion, affected side, location of the lesion, menopause, the affected side\u0026apos;s nipple discharge, the affected side\u0026apos;s nipple inversion, treatment method, local manifestations, and systemic manifestations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS version 27.0 was used for the statistical analysis. Fisher\u0026apos;s exact or Pearson\u0026apos;s chi-squared test were used for intergroup comparisons, while numbers and percentages were used to present categorical data. Groups were compared using the independent two-sample t-test or Mann-Whitney U test, and continuous data was presented as median (range) or mean \u0026plusmn; standard deviation (mean \u0026plusmn; SD). The normality of the data distribution was evaluated using the Kolmogorov\u0026ndash;Smirnov test. Multivariate analysis was conducted through logistic regression. A risk prediction nomogram was constructed using the rms package in R Studio version 4.2.2. Bootstrap resampling (1,000 iterations) was performed for internal validation. ROC curves, calibration plots, and decision curve analysis were used to assess the model\u0026apos;s clinical utility and predictive performance. P value \u0026lt; 0.05 qualified as statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical data of patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom January 2019 to June 2023, 316 patients who were cured of GLM were enrolled in the study. Of the initial study population, 29 patients were lost to follow-up, resulting in a final cohort of 287 patients for analysis. From 13.27 to 67.9 months, the median follow-up was 35.63 months. Recurrence accounted for 36 patients (12.5%) and non-recurrence for 251 (87.5%). Among the study population, six patients presented with psychiatric comorbidities. A history of tuberculosis or documented exposure was noted in three patients. Autoimmune conditions were reported in six patients, of whom five had rheumatic diseases, and one had ankylosing spondylitis. Surgical treatment was given to 102 patients, triple anti-tuberculosis drug therapy to 100, and combined treatment to 85. No severe adverse reactions were observed during the treatment process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIdentification of\u003c/strong\u003e \u003cstrong\u003erisk factors for GLM recurrence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the univariate regression analysis, factors significantly linked to GLM recurrence (P \u0026lt; 0.05) included nipple discharge on the affected side (1 = yes, 0 = no), nipple inversion on the affected side (1 = yes, 0 = no), treatment approach (1 = surgical treatment, 2 = triple anti-tuberculosis drug therapy, 3 = combined treatment), and age. There were no differences between the recurrence and non-recurrence groups for the other variables (P \u0026gt; 0.05). (Tabel 1). The multivariate logistic regression analysis includes the factors that showed statistical significance in the univariate analysis. Table 2 presents the multivariate analysis results, indicating that nipple discharge, nipple inversion (both on the affected side), surgical intervention, and younger patient age were significantly associated with an increased risk of GLM recurrence (P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEstablishment of a risk prediction model for GLM recurrence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing the independent risk factors identified through multivariate analysis, a predictive nomogram was constructed to estimate the risk of GLM recurrence in individual patients (Fig. 1). The calibration curve and the ideal reference line showed strong concordance when the model was internally validated using bootstrap resampling. The Hosmer\u0026ndash;Lemeshow goodness-of-fit test yielded no statistical significance (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05), indicating adequate model calibration (Fig. 2). The area under the ROC curve for GLM recurrence was 0.805 (95% CI: 0.737\u0026ndash;0.872), with a cutoff value of 0.171, sensitivity of 81.7%, and specificity of 66.7%, indicating good discrimination ability of the model (Fig. 3). The decision curve analysis (DCA) indicated that the nomogram provides a net clinical benefit across a range of threshold probabilities, supporting its potential utility in clinical decision-making (Fig. 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe mechanisms underlying GLM recurrence are currently unclear, and little is known regarding the risk factors. Consistent with this, no standardized approach has been established for managing recurrent GLM. Since 2019, our center has implemented a treatment protocol combining surgical intervention with a triple anti-tuberculosis drug regimen for patients diagnosed with GLM. Using a single-center patient cohort, we looked at the risk factors for GLM recurrence in this study to identify patients who were at high risk of relapsing after being cured and to develop early intervention and prevention strategies.\u003c/p\u003e \u003cp\u003eNipple inversion refers to the inability of the nipple to protrude normally beyond the plane of the areola, resulting in inward retraction. It can impair duct morphology and prevent the expulsion of breast tissue secretions and metabolic products from the ducts, resulting in blockage of the milk ducts. The metabolic byproducts invade the duct walls and leak into the interstitial tissue of the lobules, eventually triggering T-cell-mediated immune responses and granuloma formation, which result in chronic sterile inflammation.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Additionally, nipple inversion makes it difficult to maintain local hygiene, allowing oils, dirt, and secretions to collect and serve as a favorable medium for bacterial growth, which can easily lead to infections. Hua et al.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e identified nipple inversion as an independent risk factor for GLM recurrence. Additionally, our study found that patients with nipple inversion had a 2.357-fold increased risk of GLM recurrence compared to those without. Even after clinical cure, inversion-induced ductal obstruction increased the risk of recurrence or the development of new lesions. Therefore, nipple inversion traction should be performed during the surgical intervention for GLM to minimize the risk of postoperative recurrence.\u003c/p\u003e \u003cp\u003eNipple discharge can increase the risk of retrograde bacterial infection by exposing the milk ducts to the external environment. In our study, 16.4% of the patients (47 out of 287) showed nipple discharge. Yuan et al. considered bacterial infection as a possible etiological factor for GLM.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e In addition, Tian et al.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e reported that patients with purulent nipple discharge had a 3.356-fold higher risk of GLM recurrence compared to those with normal nipples. Although we did not detect any association between BMI and GLM recurrence, Huang et al.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e suggested that obese or overweight women may be at a higher risk of GLM recurrence. This is not surprising given that the adipose tissue plays a crucial role in endocrine function, and adipokines influence local estrogen receptors. An increase in adipokines may lead to elevated estrogen levels in the breast tissue, thereby promoting secretion and dilation of the milk ducts and triggering local inflammatory responses.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Furthermore, several studies\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e have suggested a potential association between hyperprolactinemia and the development of GLM. Therefore, it is essential to closely monitor prolactin levels in patients with nipple discharge. In addition, hyperprolactinemia can be managed with drugs such as bromocriptine. For patients with nipple discharge, if the diseased tissue invades the main duct during surgery, the ductal system behind the areola should be excised simultaneously to reduce the risk of recurrence.\u003c/p\u003e \u003cp\u003eDespite the availability of various treatment options for GLM, a universally accepted standardized treatment protocol has yet to be established. Previous studies\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e have indicated a correlation between treatment methods and GLM recurrence, which is also consistent with our findings. Surgical intervention was associated with the highest recurrence risk among the three treatment methods discussed herein. Surgical treatment is currently the most widely adopted approach, providing rapid symptom relief. The chance of recurrence following surgery can be as high as 50%,\u003csup\u003e21, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, most likely because it is difficult to accurately delineate the lesions visually during surgery. Asoglu et al.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e reported that complete excision of GLM lesions could significantly reduce postoperative recurrence rates. For lesions occupying a large volume of breast tissue, extensive excision is often necessary to ensure treatment efficacy and prevent recurrence, which, however, can significantly affect breast appearance and cause substantial physical and psychological trauma to the patient.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe occurrence of GLM is associated with \u003cem\u003eCorynebacteria\u003c/em\u003e, particularly \u003cem\u003eC. kroppenstedtii\u003c/em\u003e.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Co et al.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e successfully isolated \u003cem\u003eC. kroppenstedtii\u003c/em\u003e from the lesions of patients with recurrent GLM and identified it as an independent risk factor for recurrence. Although we did not compare the status of \u003cem\u003eCorynebacteria\u003c/em\u003e between the patient groups, triple anti-tuberculosis therapy with or without surgical intervention lowered the risk of recurrence, which can be attributed to the anti-bacterial effects of the drugs. Interestingly, we found no discernible difference between patients receiving combination therapy and those receiving anti-tuberculosis drugs alone. This may be due to the longer duration of the drug therapy alone (6\u0026ndash;9 months) compared to that of the combined treatment (1\u0026ndash;3 months). Zhou et al.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e also reported that triple anti-tuberculosis therapy resulted in a 78.51% cure rate for GLM, with a recurrence rate of under 10%. Therefore, choosing the appropriate treatment plan is crucial for preventing GLM recurrence. For patients undergoing surgery to achieve prompt symptom relief, a postoperative regimen of sequential triple anti-tuberculosis therapy could prove effective.\u003c/p\u003e \u003cp\u003eThe impact of age on GLM recurrence has been analyzed in numerous studies. Consistent with our findings, Li et al.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e identified age as a risk factor for GLM recurrence that is independent and found that younger patients had a relatively higher risk of relapse. While the reason for increased recurrence in younger GLM patients remains uncertain, Huang et al. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e observed that an elevated follicle-stimulating hormone (FSH) to luteinizing hormone (LH) ratio was associated with a higher probability of recurrence. Younger patients may experience perturbations in sex hormones such as FSH and LH due to more active ovarian function, which in turn can affect the breast. Therefore, greater attention should be given to younger patients with GLM.\u003c/p\u003e \u003cp\u003ePrevious studies\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e have shown that lesion size, location, quadrant of the lesion, presence of abscesses, ulceration, sinus formation, and local inflammation are not risk factors for GLM recurrence, which aligns with our study's results. Although we did not observe any association between GLM recurrence and oral contraceptive use or smoking, Tasci et al.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e found that oral contraceptive use was more common in the group experiencing recurrence compared to the group without recurrence. In addition, Co et al.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e identified smoking as an independent risk factor for GLM recurrence. Such inconsistencies may be due to the small sample size of the present study and will have to be addressed in future research with a larger sample size.\u003c/p\u003e \u003cp\u003eWe developed a nomogram model to predict GLM recurrence based on four independent risk factors: age, treatment method, nipple discharge on the affected side, and nipple inversion on the affected side. The model showed high discriminatory ability and clinical applicability, and the calibration curve closely aligned with the ideal curve, demonstrating a good fit between the predicted and actual outcomes.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study had a few limitations that ought to be considered. Due to the study's retrospective design and its single-center setting, we could not gather data from patients who were lost to follow-up. In addition, we did not identify \u003cem\u003eCorynebacteria\u003c/em\u003e in the patient samples through culture. Moreover, the nomogram model only underwent internal validation and must be validated in an external cohort to improve its accuracy. Hence, future studies should prioritize multicenter, large-scale prospective randomized controlled trials to offer fresh insights into preventing GLM recurrence.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe independent risk factors for GLM recurrence are younger age, surgical treatment, nipple discharge on the affected side, and nipple inversion on the affected side. Appropriate treatment methods should be employed for GLM management, with a particular focus on correcting nipple inversion and eliminating nipple discharge. In addition, younger patients should be considered at high risk for recurrence. The nomogram model, developed using the aforementioned factors, exhibited strong accuracy and could assist in early detection of high-risk groups for GLM recurrence, enabling prompt intervention to lower recurrence risk.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGLM Granulomatous lobular mastitis\u003c/p\u003e\n\u003cp\u003eROC Receiver operating characteristic\u003c/p\u003e\n\u003cp\u003eAUC Area under the curve\u003c/p\u003e\n\u003cp\u003eDCA Decision curve analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI Body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFSH Follicle-stimulating hormone\u003c/p\u003e\n\u003cp\u003eLH Luteinizing hormone\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoyu Shang, Jing Feng, and Yi Zhou conceptualized and oversaw the study. Boyu Shang, Tianyi Zhang, Chang Liu,\u0026nbsp;Zonglin Yuan, and\u0026nbsp;Yao\u0026nbsp;Wang\u0026nbsp;handled data collection and organization. Jing Feng and Boyu Shang conducted statistical analysis and data interpretation. Boyu Shang wrote the initial manuscript, with revisions for key content provided by Yi Zhou and Jing Feng.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Natural Science Foundation of Heilongjiang Province of China (YQ2020H012), the Research and Innovation Fund of the First Affiliated Hospital of Harbin Medical University (2020B12), the China Postdoctoral Science Foundation (2020M670927), \u0026nbsp;and the Heilongjiang Province Postdoctoral Fund (LBH-Z19171).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and informed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Board of the First Affiliated Hospital of Harbin Medical University (Reference No. 2024182) and complied with the Declaration of Helsinki guidelines. It was logged with the US Clinical Trial Registry (ID: NCT06565845) on August 21, 2024. Written informed consent was secured from all participants, with parental or legal guardian consent obtained for individuals under 16 years old.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm they have no financial conflicts or personal relationships that might have influenced the conduct or results of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eTan Q, Tay S, Gudi M, Nadkarni N, Lim S, Chuwa E. Granulomatous Mastitis and Factors Associated with Recurrence: An 11-Year Single-Centre Study of 113 Patients in Singapore. World journal of surgery. 2019;43(7):1737-45.\u003c/li\u003e\n \u003cli\u003eYuan Q-Q, Xiao S-Y, Farouk O, Du Y-T, Sheybani F, Tan QT, et al. Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition). 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Journal of Inflammation Research. 2023;Volume 16:4347-61.\u003c/li\u003e\n \u003cli\u003eSaraiya N, Corpuz M. Corynebacterium kroppenstedtii: a challenging culprit in breast abscesses and granulomatous mastitis. Current opinion in obstetrics \u0026amp; gynecology. 2019;31(5):325-32.\u003c/li\u003e\n \u003cli\u003eWilliams M, McClintock A, Bourassa L, Laya M. Treatment of Granulomatous Mastitis: Is There a Role for Antibiotics? European journal of breast health. 2021;17(3):239-46.\u003c/li\u003e\n \u003cli\u003eCo M, Cheng V, Wei J, Wong S, Chan S, Shek T, et al. Idiopathic granulomatous mastitis: a 10-year study from a multicentre clinical database. Pathology. 2018;50(7):742-7.\u003c/li\u003e\n \u003cli\u003eLi Q, Wan J, Feng Z, Shi J, Wei W. Predictive Significance of the Preoperative Neutrophil-lymphocyte Ratio for Recurrence in Idiopathic Granulomatous Mastitis Patients. The American surgeon. 2023;89(12):5577-83.\u003c/li\u003e\n \u003cli\u003eCiftci A, B\u0026uuml;k \u0026Ouml;, Yemez K, Polat S, Yazıcıoğlu İ. Risk Factors and the Role of the Albumin-to-Globulin Ratio in Predicting Recurrence Among Patients with Idiopathic Granulomatous Mastitis. Journal of inflammation research. 2022;15:5401-12.\u003c/li\u003e\n \u003cli\u003eTasci H, Turk E, Erinanc O, Erkan S, Gundogdu R, Karagulle E. Factors Affecting Recurrence of Idiopathic Granulomatous Mastitis. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2022;32(2):161-5.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Results of univariate analysis of risk factors for GLM.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eRecurrence (\u003cem\u003en\u003c/em\u003e = 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eNo recurrence (\u003cem\u003en\u003c/em\u003e = 251)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eTest statistic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eAge (years), (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e30.035\u0026plusmn;6.553\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e33.885\u0026plusmn;7.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-2.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e), (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e24.585\u0026plusmn;5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e25.625\u0026plusmn;4.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-1.602\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNumber of pregnancies (\u003cem\u003en\u003c/em\u003e), (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e1.835\u0026plusmn;1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e1.655\u0026plusmn;0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.779\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNumber of births (\u003cem\u003en\u003c/em\u003e), (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e1.085\u0026plusmn;0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e1.175\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eDiameter of the target lesion (cm), (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5.135\u0026plusmn;2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e5.365\u0026plusmn;2.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eFollow-up time (months), median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e40.02\u003c/p\u003e\n \u003cp\u003e(14.96,67.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e35.20(13.27,67.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-1.486\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eLactation \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e3.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e27(75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e217(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e9(25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e34(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNipple discharge on the affected side \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e8.267\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e27(75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e20(8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e9(25.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e231(92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNipple inversion on the affected side \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e7.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e23(63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e99(39.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e13(36.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e152(60.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eReproductive history \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e3.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.076\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e32(88.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e243(96.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e4(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e8(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eRecent history of breast trauma \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.271\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e17(47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e143(57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e19(52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e108(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eSmoking \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.752\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e2(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e11(4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e34(94.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e240(95.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eHistory of mastitis during lactation \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.911\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e1(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e12(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e35(97.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e239(95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eHistory of autoimmune disease \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e4.623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.139\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e1(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e5(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e35(97.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e246(98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eHistory of tuberculosis and exposure to tuberculosis \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e3(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e36(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e248(98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eMental disorders \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e6(2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e36(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e245(97.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eOral Contraceptive pills \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e5(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e36(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e246(98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eMenopause \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.463\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e10(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e36(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e241(96.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eSide \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e20(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e118(47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e16(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e125(49.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eBilateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e8(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLesion location \u003cem\u003en\u003c/em\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.801\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eUpper outer quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e10(27.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e55(21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eLower outer quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e3(8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e26(10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eUpper inner quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e7(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e50(19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eLower inner quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e3(8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e25(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eMultiple quadrants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e8(22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e74(29.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eRetroareolar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5(13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e21(8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapeutic modality \u003cem\u003en\u003c/em\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e18.635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eSurgical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e24(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e78(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eTriple anti-tuberculosis drug therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e4(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e96(38.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eCombination therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e8(22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e77(30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocal manifestations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eMass \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.999\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e36(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e247(98.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e4(1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003ePain \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e27(75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e166(66.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e9(25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e85(33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eAbscess \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.545\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.214\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e16(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e85(33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e20(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e166(66.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eUlceration \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e12(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e78(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e24(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e173(68.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eTenderness \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e31(86.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e209(83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e5(13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e42(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eSinus formation \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.544\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e3(8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e34(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e33(91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e217(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eInflammatory hyperemic skin \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.543\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e23(63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e147(58.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e13(36.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e104(41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eEdema \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.229\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e25(69.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e148(59.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e11(30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e103(41.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSystemic symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eArthralgia \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e1.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.249\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e1(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e26(10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e35(97.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e225(89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eErythema nodosum \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.999\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e2(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e15(6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e34(94.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e236(94.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eFever \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026gt;0.999\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e3(8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e23(9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e33(91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e228(90.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eTable 2. Results of multivariate logistic analysis of risk factors for GLM.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"71%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003eWald\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eNipple discharge on the affected side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e1.720\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e9.856\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e5.584 (1.908\u0026ndash;16.341)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eNipple inversion on the affected side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e1.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e6.320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e2.792 (1.254\u0026ndash;6.216）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapeutic modality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eSurgical treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eTriple anti-tuberculosis drug therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-2.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e14.246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.110 (0.035\u0026ndash;0.346)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eCombination therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-1.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e9.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.207 (0.077\u0026ndash;0.554)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e10.295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.908 (0.856\u0026ndash;0.963）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Granulomatous lobular mastitis, Recurrence risk factors, Prediction model, ROC curve","lastPublishedDoi":"10.21203/rs.3.rs-6759384/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6759384/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e To explore the risk factors that are associated to the recurrence of granulomatous lobular mastitis (GLM) after treatment and to develop a nomogram model that can predict the risk of recurrence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Medical records and follow-up data from GLM patients treated at our facility were retrospectively analyzed. In order to identify independent risk factors for GLM recurrence, the patients were split into groups with and without recurrence using univariate and multivariate logistic regression analyses. A predictive nomogram model was built using these variables, and its performance was evaluated by plotting the calibration curve, receiver operating characteristic (ROC), area under the curve (AUC), and decision curve analysis (DCA) curves.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We evaluated the data of 287 GLM patients, of which 36 patients (12.5%) experienced recurrence, while the remaining 251 patients (87.5%) were included in the non-recurrence group. The affected side's nipple discharge was detected using multivariate logistic regression, nipple inversion on the affected side, surgical treatment, and younger age as the independent risk factors for recurrence (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). The model had an AUC of 0.805 (95% CI: 0.737–0.872), 81.7% sensitivity, and 66.7% specificity. The calibration curve was consistent with the ideal curve, and the DCA indicated good clinical utility of the model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Independent risk factors for GLM recurrence include younger age, surgical treatment, nipple discharge on the affected side, and nipple inversion on the affected side. The nomogram based on these factors demonstrated good predictive value for GLM recurrence.\u003c/p\u003e","manuscriptTitle":"Analysis of the therapeutic effect and side effects of drug treatment for granulomatous lobular mastitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 09:27:42","doi":"10.21203/rs.3.rs-6759384/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-26T08:57:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T08:30:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-16T00:16:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2902121560217246248436974259692606297","date":"2025-06-13T09:27:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258110750159306195253944644040710374648","date":"2025-06-13T02:35:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-13T02:27:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-28T05:51:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-28T05:47:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-05-27T12:12:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4dfe8116-066f-4f38-81af-69f08a448803","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T07:39:00+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 09:27:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6759384","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6759384","identity":"rs-6759384","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}