Objective: In this study, we aimed to investigate the incidence and risk factors for interstitial nephritis in patients with ankylosing spondylitis (AS). Methods: We retrospectively analyzed the claims records of patients diagnosed with AS in Korea’s Health Insurance Review and Assessment Service Database between 2016 and 2019. The Assessment of Spondyloarthritis International Society nonsteroidal anti-inflammatory drugs (NSAIDs) intake score was used to calculate the NSAID dosage over 1 year after AS diagnosis. The incidence rate of interstitial kidney disease was calculated as the number of events per 1,000 person-years. The risks associated with sex, age, Charlson Comorbidity Index, comorbidities, and concomitant medications were assessed using the Cox proportional hazards model, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In total, 11,749 patients with AS were included in this study. Of these, 79 patients had interstitial nephritis, with an incidence rate of 2.50 per 1,000 person-years. In multivariable analysis, female sex (HR, 2.44; 95% CI, 1.56~3.83), hypertension (HR, 2.08; 95% CI, 1.15~3.76), and renal failure (HR, 3.70; 95% CI, 1.30~10.55) showed significant associations. However, NSAID use in the first year after AS diagnosis was not associated with interstitial nephritis occurrence. Conclusion The incidence of interstitial nephritis in patients with AS was 2.50 per 1,000 person-years, with female sex and comorbidities identified as significant risk factors. However, NSAID use during the first year after AS diagnosis was not associated with interstitial nephritis development.

Background: Farnesoid X receptor (FXR) is known to play important roles in glucose and lipid metabolism. We aimed to evaluate effects of FXR agonist on metabolic disorders in db/db mice. Seven week-old db/db mice were injected FXR agonist GW4064 (30 mg/kg/day) or carrier solution (dimethyl sulfoxide) intraperitoneally for 4 weeks. Body weight, food intake, and blood glucose levels were measured weekly. Glucose tolerance test and insulin tolerance test were performed at the end of study. Hepatic genes involed in lipogenesis and gluconeogenesis were analyzed by real time polymerase chain reaction. Endoplasmic reticulum stress markers were analyzed by western blot. Results: GW4064 treatment significantly attenuated weight gain, and improved glucose intolerance and insulin resistance in db/db mice. In addition, GW4064 treatment significantly repressed hepatic steatosis. GW4064 treatment significantly lowered hepatic gene expression of phosphoenolpyruvate carboxykinase 1, glucose 6-phosphatase, and sterol regulatory element binding protein 1c. GW4064 treatment significantly lowered the protein levels of ATF6, CHOP, Caspase3, and Cleaved Caspase3 in liver. FXR agonist GW4064 showed beneficial effects on weight gain, glucose intolerance, insulin resistance, hepatic steatosis, and hepatic ER stress. Conclusions These findings suggest that FXR agonists are promising therapeutic agents for treatment of various metabolic disorders.

Purpose: Oncologic and surgical outcomes of robot-assisted nipple-sparing mastectomy (RNSM) compared to conventional nipple-sparing mastectomy (CNSM) is under investigation. This study compared the clinical outcomes of recurrence-free survival and postoperative complication after RNSM and CNSM. Materials and Methods: We retrospectively reviewed data of 401 patients who underwent da Vinci Si/Xi/SP-assisted RNSM or CNSM with immediate reconstruction between November 2016 and November 2020 at a single institute. Oncological outcomes were collected until March 2022. Primary endpoints were long-term outcomes, such as local recurrence, distant metastasis, disease-free survival, overall survival, and postoperative complications, while secondary endpoints were pathology results, and oncological outcomes. Results: Patients underwent RNSM (n=162) or CNSM (n=239). Of RNSM cases, 9 (5.6%) were performed using the da Vinci Si System, 96 (59.3%) using the da Vinci Xi System, and 57 (35.2%) using the da Vinci SP System. No significant difference in recurrence-free survival was found between the RNSM and CNSM group, and both groups had a median follow-up of 37 months. The recurrence rate in RNSM patients after a median follow-up of 24.5 months was 3.8%, compared with 5.9% in CNSM patients after a median follow-up of 42 months. No difference in recurrence was seen among RNSM patients with respect to surgical systems (multiport vs. SP, p =0.136). In addition, grade III postoperative complication rate was lower in patients with RNSM than in those with CNSM. Transfusion was only applied in 6.2% of patients. Conclusion Robot-assisted surgical systems can be safely used to perform nipple-sparing mastectomy in patients with early breast cancer.

Objectives: . Differentiated thyroid cancer (DTC) has a favorable prognosis. However, indeterminate lymph nodes (LNs) are common, making it challenging to distinguish recurrent from persistent DTC. Previous studies have not specifically compared the prognosis between recurrent and persistent DTC. Therefore, we aimed to compare prognosis and oncologic characteristics between these two groups. Methods: . This retrospective cohort study was conducted at a single tertiary care institution and included 265 patients with DTC (recurrent, 109; persistent, 156) who underwent reoperation between November 1, 1999, and August 31, 2018, for structural disease. Patients with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncological characteristics, patterns of LN metastasis, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. For DFS, time zero was defined as the date of the second operation. Results: . Recurrent DTC had a higher incidence of central LN metastasis (P=0.003), infield recurrence (P<0.001), and distant metastasis (P<0.001). In contrast, persistent DTC more frequently exhibited lateral LN metastasis (P=0.003) and outfield recurrence (P<0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) in recurrent DTC and ipsilateral level IV (43.0%) in persistent DTC. Ten-year DFS was significantly lower in recurrent DTC than in persistent DTC (41.0% vs. 67.9%; P<0.001). Recurrent DTC, older age, a higher number of metastatic LNs at the second operation (first reoperation), and R1/R2 resection at the second operation were associated with decreased DFS. OS did not significantly differ between recurrent and persistent DTC (P=0.160). Conclusion . Recurrent DTC is associated with poorer DFS than persistent DTC, although OS does not significantly differ between the two groups.

Background: Preclinical studies have reported anticancer properties of sodium-glucose cotransporter 2 inhibitors (SGLT2is). We aimed to elucidate the association between the use of SGLT2is and the risk of prostate cancer among male patients with type 2 diabetes mellitus (T2DM). Methods: An active-comparator, new-user cohort design using a nationwide database between September 2014 and June 2020 was conducted on 45,601 new SGLT2i users and 205,395 new users of other glucose-lowering medications (oGLMs). In the following 1:1 propensity score matched (PSM) analysis, 35,371 SGLT2i users matched with an equivalent number of oGLM users were assessed. The hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer were calculated. Results: Among the cohort, prostate cancer was diagnosed in 210 out of 45,601 SGLT2i users, corresponding to a cumulative incidence of 1.0%, in contrast to 1,880 cases among 205,395 users of oGLMs, with a cumulative incidence of 1.5%. The use of SGLT2is was significantly correlated with a reduced risk of prostate cancer based on a multivariable-adjusted HR of 0.83 (95% CI, 0.71 to 0.98). PSM analysis affirmed 18% reduction in prostate cancer risk associated with SGLT2i use (HR, 0.82; 95% CI, 0.67 to 0.99). Subgroup analyses revealed that body mass index (BMI) significantly influenced the effect of SGLT2i on prostate cancer risk, with a more pronounced reduction in the subgroup with a BMI <25 kg/m2 (P=0.037). Conclusion The use of SGLT2is in Korean male patients with T2DM is associated with a lower risk of prostate cancer.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Objective: Using a nationally representative cohort of medical claims data in Korea, this study aimed to analyze the association between the use of various anti-rheumatic agents and the risk of acute myocardial infarction (AMI) in patients with rheumatoid arthritis (RA). Methods: This nested case-control study used the Korean Health Insurance Review and Assessment data of 35,133 patients newly diagnosed with RA between 2011 and 2020. Incident AMI patients were identified and matched at a 1:4 ratio with randomly selected controls. The usage of anti-rheumatic agents was measured from the date of RA diagnosis to the index date and stratified based on exposure time and duration. The risk of AMI associated with each anti-rheumatic agent was estimated using conditional logistic regression, adjusted for comorbidities and concomitant drug use. Results: Of the 35,133 patients with RA, 484 were diagnosed with AMI. In total, 484 AMI patients and 1,924 controls with newly diagnosed RA were included in the analysis. Current exposure and long-term exposure to glucocorticoids (adjusted odds ratio [aOR]: 2.301, 95% confidence interval [CI]: 1.741~3.041; aOR: 1.792, 95% CI: 1.378~2.330) and leflunomide (aOR: 1.525, 95% CI: 1.196~1.944; aOR: 1.740, 95% CI: 1.372~2.207) were associated with an increased risk of AMI. Conclusion The study demonstrates a significant association between the current and long-term use of glucocorticoids and leflunomide and an increased risk of AMI in patients with RA. These findings underscore the importance of careful consideration of cardiovascular risks when selecting anti-rheumatic agents for RA treatment.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Background/Aims: We investigated the incidences of overall and site-specific malignancies and chemopreventive effects of statin, metformin, and aspirin in patients with ulcerative colitis. Methods: We collected data using the Health Insurance Review and Assessment claims database from January 2007 to April 2020. Results: The overall malignancy risk among the 35,189 ulcerative colitis patients was similar to that of the general population (standardized incidence ratio, 0.94; 95% confidence interval, 0.88–1.00). In male patients, standardized incidence ratios were high for thyroid cancer and low for stomach cancer, colorectal cancer, liver cancer, and lung cancer. Concurrently, standard incidence ratios were high for liver cancer and central nervous system cancer in female patients. While 122 cases of colorectal cancer occurred in the study patients, the standardized incidence ratio was 0.83 (95% confidence interval, 0.69–0.99). Treatment for ulcerative colitis was not associated with an increased adjusted hazard ratio, while comorbidities increased it for all malignancies. Treatment for ulcerative colitis was associated with an increased adjusted hazard ratio, while comorbidities did not increase it for colorectal cancer. After adjusting for age, sex, comorbidities, and ulcerative colitis treatment, statins showed a dose-dependent chemopreventive effect for all malignancies (P=0.002), while metformin and aspirin did not show any. Conclusions In ulcerative colitis patients, standardized incidence ratios for all malignancies and colorectal cancer did not increase. Adjusted hazard ratios for all malignancies increased with comorbidities and those for colorectal cancer with ulcerative colitis treatment. Statins have a dose-dependent chemopreventive effect for all malignancies.

Background: In Korea, the patterns of prevalence of gynecological cancers have shifted due to rising obesity-related cancer cases. We evaluated the associations of body mass index (BMI) and waist circumference (WC) with the risk of gynecological malignancy in Korean women. Methods: Using National Health Insurance Service cohort data, we analyzed 365,581 participants among the 1,999,980 women aged ≥ 19 years who underwent health check-ups at the baseline year 2009–2010, excluding those who died, those with prior cancer diagnoses, underwent hysterectomy and/or salpingo-oophorectomy before the index date (January 1st, 2011), or missing/outliers BMI and WC values. Follow-up extended to December 31st, 2021, evaluating the incidences of endometrial, ovarian, and cervical cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) for each gynecological malignancy according to BMI and WC were calculated using Cox proportional hazard regression. Results: Among the 365,581 participants, 898, 1,268, and 873 cases of endometrial, ovarian, and cervical cancer occurred, respectively. HRs (95% CIs) for endometrial cancer were 1.37 (1.15–1.63), 1.63 (1.38–1.94), and 3.64 (2.81–4.70) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend < 0.001). HRs (95% CIs) for ovarian cancer were 1.16 (1.00–1.33), 1.19 (1.03–1.37), and 1.49 (1.12–1.98) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend = 0.002). No significant association was found between BMI and the risk for cervical cancer (P for trend = 0.266). HRs (95% CIs) for endometrial cancer were 1.35 (1.09–1.66), 1.41 (1.14–1.74), and 1.90 (1.55–2.34) for the 2nd, 3rd, and 4th quartiles of WCs compared to the 1st quartile (P for trend <0.001). Ovarian cancer tended to increase and cervical cancer tended to decrease as WC increased (P for trend = 0.035 for ovarian cancer, P for trend = 0.034 for cervical cancer). Conclusion In Korean women, the risks of endometrial and ovarian cancers increased significantly from the pre-obese level as BMI and WC increased, while cervical cancer risk tended to increase as WC decreased. Management of obesity should be reinforced for the prevention of obesity-related gynecological cancers, considering the increasing incidence of these cancers among Korean women.