Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer.

PURPOSE: Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. METHODS: PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. RESULTS: In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. CONCLUSION: Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

Urolithiasis in Kidney Transplant Patients: A Multicenter KSER Research Series.

Background and Objectives: Urolithiasis occurrence is uncommon in kidney transplantation patients, though it has serious implications, including acute kidney injury in the transplanted kidney. This study investigates the leading causes of urolithiasis in kidney transplantation patients, the diagnostic process, and the outcomes of multimodal management. Materials and Methods: Data collection spanned from January 1997 to December 2021, involving kidney transplantation patients with urolithiasis from the database of the Korean Society of Endourology and Robotics (KSER) research committee. Analysis encompassed factors triggering urolithiasis, the diagnostic process, stone attributes, treatment methods, and outcomes. Results: Our analysis included 58 kidney transplantation patients with urolithiasis from eight medical centers. Of these patients, 37 were male and 4 had previous urolithiasis diagnoses. The mean age was 59.09 ± 10.70 years, with a mean duration from kidney transplantation to diagnosis of 76.26 ± 183.14 months. The most frequent method of stone detection was through asymptomatic routine check-ups (54.7%). Among the 58 patients, 51 underwent stone treatment. Notably, 95.3% of patients with ureter stones received treatment, a significantly higher rate than the 66.7% of patients with renal stones (p = 0.010). Success rates showed no significant differences between renal (70%) and ureter stone (78.0%) groups (p = 0.881). Conclusions: Urolithiasis in transplanted kidneys constitutes an acute condition requiring emergency intervention. Endo-urological interventions are effective for kidney transplantation patients with urolithiasis. To ensure prevention and early detection, diligent follow-up and routine imaging tests are necessary.

Sialylated IVIg binding to DC-SIGN+ Hofbauer cells induces immune tolerance through the caveolin-1/NF-kB pathway and IL-10 secretion.

Although the use of IVIg has increased in various immune-driven diseases and even in pregnancy, the exact action mechanisms of IVIg are not fully understood. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) is a known receptor for α-2,6-sialylated IgG (sIVIg), which is responsible for the anti-inflammatory effect of IVIg. DC-SIGN is expressed on Hofbauer cells (HBCs) of the fetal villi of the placenta which act as an innate immune modulator at the maternal-fetal interface. Preeclampsia is a major complication in pregnancy and is related to IL-10, a cytokine with an important role in immune tolerance. DC-SIGN interaction with sIVIg in HBCs promoted IL-10 secretion through the activation of the caveolin-1/NF-κB pathway, especially in plasma lipid rafts. Consistent results were obtained for HBCs from patients with preeclampsia. Collectively, the stimulation of DC-SIGN+ HBCs with sIVIg enhanced immune tolerance in the feto-maternal environment, suggesting the therapeutic application of sIVIg to prevent preeclampsia.

The increased risk of colorectal cancer in the women who underwent hysterectomy from the South Korean National Health Insurance Database.

BACKGROUND: Several population-based studies and observational studies have shown that oophorectomy is associated with an increased risk of colorectal cancer (CRC), and hormone replacement therapy has been associated with a reduction in the risk of colorectal cancer. This study was carried out to investigate whether hysterectomy, which may affect the levels of female hormones, is associated with a risk of cancer of the specific gastrointestinal tract. METHODS: This population-based retrospective cohort study was conducted using insurance data provided by the Health Insurance Review and Assessment Service (HIRA) from January 1, 2007, to December 31, 2020. The hysterectomy group included 40- to 59-year-old women who underwent hysterectomy with uterine leiomyoma or uterine endometriosis from January 1, 2011, to December 31, 2014. The control group included women aged 40 to 59 years who visited medical institutions for medical examination from January 1, 2011 to December 31, 2014. RESULTS: The hysterectomy and non-hysterectomhy groups comprised 66,204 and 89,768 subjects, respectively. The median ages in the non-hysterectomy group and hysterectomy group were 48 (range: 43-53) and 46 (range: 44-49) years, respectively. In the unadjusted results of the analysis, all colorectal cancer (CRC) increased in the hysterectomy alone group (HR 1.222, 95% confidence interval (CI) 1.016-1.47, p = 0.033), sigmoid colon cancer increased in the hysterectomy alone group (HR 1.71, 95% CI 1.073-2.724, p = 0.024), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.924, 95% CI 1.073-2.724, p = 0.002). The adjusted results showed that all CRC increased in the hysterectomy alone group (HR 1.406, 95% CI 1.057-1.871, p = 0.019), colon cancer increased in the hysterectomy alone group (HR 1.523, 95% CI 1.068-2.17, p = 0.02), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.933, 95% CI 1.131-3.302, p = 0.016). The all-cause mortality of GI cancer increased in the hysterectomy alone group (HR 3.495, 95% CI 1.347-9.07, p = 0.001). CONCLUSIONS: This study showed that the risk of all CRC increased in women who underwent hysterectomy compared with women who did not. In particular, the risk of rectal cancer was significantly higher in the women who underwent hysterectomy with adnexal surgery than in the controls. There was no association between hysterectomy and other GI cancers.

Combination therapy with tamsulosin and traditional herbal medicine for lower urinary tract symptoms due to benign prostatic hyperplasia: A double-blinded, randomized, pilot clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.

Is PSA density of the peripheral zone as a useful predictor for prostate cancer in patients with gray zone PSA levels?

BACKGROUND: Serum prostate-specific antigen (PSA) is widely used in screening tests for prostate cancer. As the low specificity of PSA results in unnecessary and invasive prostate biopsies, we evaluated the clinical significance of various PSAs and PSA density (PSAD) related to peripheral zones in patients with gray zone PSA level (4-10 ng/mL). METHODS: A total of 1300 patients underwent transrectal ultrasonography-guided prostate biopsy from 2014 to 2019. Among them, 545 patients in the gray zone were divided into the prostate cancer diagnosis group and the non-prostate cancer diagnosis group, and PSA, relative extra transitional zone PSA (RETzPSA), estimated post holmium laser enucleation of the prostate PSA (EPHPSA), PSAD, peripheral zone PSA density (PZPSAD) and extra-transitional zone density (ETzD) were compared and analyzed using receiver-operating characteristics (ROC) analysis after 1:1 matching using propensity score. RESULTS: Area under the ROC curve values of PSA, EPHPSA, RETzPSA, PSA density, ETzD, and PZPSAD were 0.553 (95% CI: 0.495-0.610), 0.611 (95% CI: 0.554-0.666), 0.673 (95% CI: 0.617-0.725), 0.745 (95% CI: 0.693-0.793), 0.731 (95% CI: 0.677-0.780) and 0.677 (95% CI: 0.611-0.719), respectively. PSAD had 67.11% sensitivity, 71.71% specificity, and 70.34% positive predictive rate at 0.18 ng/mL/cc. ETzD had 69.08% sensitivity, 64.47% specificity, and 66.04% positive predictive rate at 0.04 ng/mL/cc. When the cut-off value of PSAD was increased to 0.18 ng/mL/cc, the best results were obtained with an odds ratio of 5.171 (95% CI: 3.171-8.432), followed by ETzD with 4.054 (95% CI: 2.513-6.540). CONCLUSIONS: These results suggested that volume-adjusted parameters (ETzD and PSAD) might be more sensitive and accurate than various PSA in gray zone patients who required prostate biopsy to reduce unnecessary biopsy.

Machine learning prediction of stone-free success in patients with urinary stone after treatment of shock wave lithotripsy.

BACKGROUND: The aims of this study were to determine the predictive value of decision support analysis for the shock wave lithotripsy (SWL) success rate and to analyze the data obtained from patients who underwent SWL to assess the factors influencing the outcome by using machine learning methods. METHODS: We retrospectively reviewed the medical records of 358 patients who underwent SWL for urinary stone (kidney and upper-ureter stone) between 2015 and 2018 and evaluated the possible prognostic features, including patient population characteristics, urinary stone characteristics on a non-contrast, computed tomographic image. We performed 80% training set and 20% test set for the predictions of success and mainly used decision tree-based machine learning algorithms, such as random forest (RF), extreme gradient boosting trees (XGBoost), and light gradient boosting method (LightGBM). RESULTS: In machine learning analysis, the prediction accuracies for stone-free were 86.0, 87.5, and 87.9%, and those for one-session success were 78.0, 77.4, and 77.0% using RF, XGBoost, and LightGBM, respectively. In predictions for stone-free, LightGBM yielded the best accuracy and RF yielded the best one in those for one-session success among those methods. The sensitivity and specificity values for machine learning analytics are (0.74 to 0.78 and 0.92 to 0.93) for stone-free and (0.79 to 0.81 and 0.74 to 0.75) for one-session success, respectively. The area under curve (AUC) values for machine learning analytics are (0.84 to 0.85) for stone-free and (0.77 to 0.78) for one-session success and their 95% confidence intervals (CIs) are (0.730 to 0.933) and (0.673 to 0.866) in average of methods, respectively. CONCLUSIONS: We applied a selected machine learning analysis to predict the result after treatment of SWL for urinary stone. About 88% accurate machine learning based predictive model was evaluated. The importance of machine learning algorithm can give matched insights to domain knowledge on effective and influential factors for SWL success outcomes.

Increased expression of neuregulin 1 in the urothelium of rat bladder with partial bladder outlet obstruction.

BACKGROUND: This study determined whether changes in the expression of neuregulin (NRG) 1, erbB2 tyrosine kinase (ErbB2) and the M2 muscarinic receptor in the urothelium and detrusor muscle of the rat bladder were associated with partial bladder outlet obstruction (PBOO). METHODS: Male Sprague-Dawley rats (body weight 250-300 g) were used and subdivided into control (n = 10) and PBOO groups (n = 20). PBOO was induced for 21 days, and the expression of NRG1, ErbB2 and M2 muscarinic receptor mRNA and protein was evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting, respectively. RESULTS: In the urothelium of rat bladder samples, protein expression and mRNA expression of NRG1, ErbB2 and M2 muscarinic receptor were significantly increased in the PBOO group compared to the control group (p < 0.05). Only mRNA expression levels of NRG1/ ErbB2 were higher in the detrusor muscle of the PBOO group compared to the control group (p < 0.05). CONCLUSIONS: Our study demonstrated remarkable changes in the expression of NRG1/ErbB2 receptor mRNA and protein in the urothelium and muscle layer. These results suggest that NRG1 overexpression plays some kind of role against the PBOO-induced upregulated muscarinic receptors in detrusor overactivity.

Comparison of Loop Electrosurgical Excision Procedure Using a Ring-Shaped Loop Versus a Right-Angled Triangular Loop.

OBJECTIVE: To compare the resection margin (RM) status and postoperative severe hemorrhage using different loop electrosurgical excision procedure (LEEP) techniques for cervical intraepithelial neoplasia (CIN) 2/3 treatment. STUDY DESIGN: We retrospectively reviewed 278 patients who underwent LEEPs for CIN 2/3 treatment at our institute between 2005­2014. In type A surgery (N=148), a ring-shaped loop was used. If the first pass failed to remove the entire lesion, separate loop excisions for the intracervical portion were performed. In type B surgery (N=130), a right-angled triangular loop in a single pass was used. Surgical outcomes and postoperative severe hemorrhage were compared between the two groups. Logistic regression analysis was performed to identify the independent predictors of RM status. RESULTS: The mean LEEP depth was larger after type A surgery (2.2 vs. 2.0 cm, respectively; p=0.04). Type B surgery showed lower rate of 30-day postoperative hemorrhage (13.8% vs. 26.4%, p<0.05) and higher rate of negative RM (68.9% vs. 82.3%, p<0.05). Multivariate analysis identified the surgery type (p=0.01, OR=0.45 [0.24­0.83]) and a postoperative pathological diagnosis of CIN3 (p=0.01, OR=2.53 [1.22­5.26]) as independent risk factors for positive RM. CONCLUSION: LEEPs using a right-angled triangular loop could reduce positive RMs.

Machine learning analysis with population data for prepregnancy and perinatal risk factors for the neurodevelopmental delay of offspring.

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.

Risk of Gestational Diabetes and Pregnancy-Induced Hypertension with a History of Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study.

OBJECTIVE: To evaluate the risks of developing gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) in women with polycystic ovary syndrome (PCOS) using data from Korea's National Health Insurance Service. METHOD: The PCOS group comprised women aged 20 to 49 years diagnosed with PCOS between 1 January 2012, and 31 December 2020. The control group comprised women aged 20 to 49 years who visited medical institutions for health checkups during the same period. Women with any cancer within 180 days of the inclusion day were excluded from both the PCOS and control groups, as were women without a delivery record within 180 days after the inclusion day, as well as women who visited a medical institution more than once before the inclusion day due to hypertension, diabetes mellitus (DM), hyperlipidemia, DM in pregnancy, or PIH. GDM and PIH were defined as cases with at least three visits to a medical institution with a GDM diagnostic code and a PIH diagnostic code, respectively. RESULTS: Overall, 27,687 and 45,594 women with and without a history of PCOS experienced childbirth during the study period. GDM and PIH cases were significantly higher in the PCOS group than in the control group. When adjusted for age, SES, region, CCI, parity, multiple pregnancies, adnexal surgery, uterine leiomyoma, endometriosis, PIH, and GDM, an increased risk of GDM (OR = 1.719, 95% CI = 1.616-1.828) was observed among women with a history of PCOS. There was no increase in the risk of PIH among women with a history of PCOS (OR = 1.243, 95% CI = 0.940-1.644). CONCLUSION: A history of PCOS itself might increase the risk of GDM, but its relationship with PIH remains unclear. These findings would be helpful in the prenatal counseling and management of patients with PCOS-related pregnancy outcomes.

A Novel Incisionless Disposable Vaginal Device for Female Stress Urinary Incontinence: Efficacy and Quality of Life.

PURPOSE: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. METHODS: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. RESULTS: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. CONCLUSION: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration: The study was registered as a clinical trial (KCT0008369).

Risk of retinopathy in women with pregnancy-induced hypertension: a nationwide population-based cohort study of 9-year follow-up after delivery.

BACKGROUND: The retina is potentially associated with several physiological, hormonal, and metabolic changes during pregnancy. The few available epidemiologic studies of ocular changes in pregnancy have mainly concerned retinopathies. Pregnancy-induced hypertension, which leads to ocular manifestations including blurred vision, photopsia, scotoma, and diplopia, might induce reactive changes in the retinal vessels. Although several studies have suggested the existence of pregnancy-induced hypertension-related retinal ocular disease, there are few large cohort studies on this topic. OBJECTIVE: This study aimed to investigate the risk of major retinal diseases including central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy in the long-term postpartum stage according to the presence of previous pregnancy-induced hypertension in a large cohort based on the Korean National Health Insurance Database. STUDY DESIGN: On the basis of Korean health data, 909,520 patients who delivered from 2012 to 2013 were analyzed. Among them, patients who had previous ocular diseases or hypertension and multiple births were excluded. Finally, 858,057 mothers were assessed for central serous chorioretinopathy (ICD-10: H35.70), diabetic retinopathy (ICD-10: H36.0, E10.31, E10.32, E11.31, E11.32, E12.31, E13.31, E13.32, E14.31, E14.32), retinal vein occlusion (ICD-10: H34.8), retinal artery occlusion (ICD-10: H34.2), and hypertensive retinopathy (ICD-10: H35.02) for 9 years after delivery. Enrolled patients were divided into 2 groups: 10,808 patients with and 847,249 without pregnancy-induced hypertension. The primary outcomes were the incidence of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy 9 years after delivery. Clinical variables were age, parity, cesarean delivery, gestational diabetes mellitus, and postpartum hemorrhage. In addition, pregestational diabetes mellitus, kidney diseases, cerebrovascular diseases, and cardiovascular diseases were adjusted. RESULTS: Postpartum retinal disease during the 9 years after delivery and total retinal diseases showed higher rates in patients with pregnancy-induced hypertension. In detail, the rates of central serous chorioretinopathy (0.3% vs 0.1%), diabetic retinopathy (1.79% vs 0.5%), retinal vein occlusion (0.19% vs 0.1%), and hypertensive retinopathy (0.62% vs 0.05%) were higher than those found in patients without pregnancy-induced hypertension. After adjusting for confounding factors, pregnancy-induced hypertension was associated with development of postpartum retinopathy, with a >2-fold increase (hazard ratio, 2.845; 95% confidence interval, 2.54-3.188). Furthermore, pregnancy-induced hypertension affected the development of central serous chorioretinopathy (hazard ratio, 3.681; 95% confidence interval, 2.667-5.082), diabetic retinopathy (hazard ratio, 2.326; 95% confidence interval, 2.013-2.688), retinal vein occlusion (hazard ratio, 2.241; 95% confidence interval, 1.491-3.368), and hypertensive retinopathy (hazard ratio, 11.392; 95% confidence interval, 8.771-14.796) after delivery. CONCLUSION: A history of pregnancy-induced hypertension increases the risk of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and hypertensive retinopathy according to 9-year long-term ophthalmologic follow-up.

Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women.

Importance: Women who undergo surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron levels than those who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) at ages younger than usually seen. Examining this issue may provide important implications for women's cardiovascular health to both physicians and patients. Objective: To evaluate the association of hysterectomy with the risk of incident CVD among women before age 50 years. Design, Setting, and Participants: In this Korean population-based cohort study, 135 575 women aged 40 to 49 years were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching in covariates including age, socioeconomic status, region, Charlson Comorbidity Index, hypertension, diabetes, dyslipidemia, menopause, menopausal hormone therapy, and adnexal surgery before inclusion, 55 539 pairs were included in the hysterectomy and nonhysterectomy groups. Participants were followed up until December 31, 2020. Data analysis was conducted from December 20, 2021, to February 17, 2022. Main Outcomes and Measures: The primary outcome was an incidental CVD, a composite of myocardial infarction, coronary artery revascularization, and stroke. The individual components of the primary outcome were also evaluated. Results: A total of 55 539 pairs were included; median age in the combined groups was 45 (IQR, 42-47) years. During median follow-up periods in the hysterectomy group of 7.9 (IQR, 6.8-8.9) years and nonhysterectomy group of 7.9 (IQR, 6.8-8.8) years, the incidence of CVD was 115 per 100 000 person-years for the hysterectomy group and 96 per 100 000 person-years for the nonhysterectomy group. After adjusting for confounding factors, the hysterectomy group had an increased risk of CVD compared with the nonhysterectomy group (hazard ratio [HR], 1.25; 95% CI, 1.09-1.44). The incidences of myocardial infarction and coronary artery revascularization were comparable between the groups, whereas the risk of stroke was significantly higher in the hysterectomy group (HR, 1.31; 95% CI, 1.12-1.53). Even after excluding women who underwent oophorectomy, the hysterectomy group had higher risks of CVD (HR, 1.24; 95% CI, 1.06-1.44). Conclusions and Relevance: The findings of this cohort study suggest early menopause owing to hysterectomy was associated with increased risks for a composite of CVD, particularly stroke.

Case Report: Upper limb superficial venous thrombosis associated with oral contraceptives mimicking soft tissue mass.

Background: Venous thrombosis associated with the use of oral contraceptives (OCs) occurs mostly in the deep veins of the lower extremity. A lesion of the upper extremity is rare, and the majority of thrombotic events that occur in the superficial vein of the upper extremity are caused by intravenous catheters. We present a rare case of superficial venous thrombus on the upper extremity in a woman with a history of long-term OC use. Case presentation: A 35-year-old woman, with an 8-year history of OC use, presented with a 2-year history of painfully palpable masses on her left forearm. The lesion mimicking soft tissue mass was confirmed to be superficial venous thrombi through ultrasound and magnetic resonance imaging. Conservative treatment including non-steroidal anti-inflammatory drugs, vasoprotective agents, and aspirin was prescribed. Through consultation with the Department of Obstetrics and Gynecology, it was confirmed that the current OCs could be discontinued, and the pain was almost relieved after conservative treatment. Conclusions: If thrombotic events occur in the superficial vein of the upper extremity without intravenous catheters, detailed medical history taking and the possibility of OCs should be considered.

Association between breast diseases and symptomatic uterine fibroids by using South Korean National Health Insurance database.

Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299-1.372), 1.796 (95% CI 1.542-2.092), and 1.3 (95% CI 1.198-1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36-0.734) and living in rural areas (HR 0.889, 95% CI 0.822-0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs.

Rupture-mediated large uterine defect at 30th gestational week with protruded amniotic sac and fetal head without fetal compromise after laparoscopic electromyolysis: Case report and literature review.

BACKGROUND: We describe a case of a rupture-mediated large uterine defect, which occurred on the 30th gestation week presenting a protruding amniotic sac sac without fetal compromise after a laparoscopic electromyolysis. CASE PRESENTATION: A 28-year-old woman in her 30th week of gestation (gravida 2, para 0) presented with whole abdominal and right lower quadrant pain at Sanggye Paik Hospital. Ultrasound examination showed normal amniotic fluid and placentation but with breech presentation. She had undergone laparoscopic right ovarian cystectomy due to endometriosis 5 years earlier. Cardiotocography revealed an intermittent variable deceleration and no uterine contraction. Magnetic resonance imaging ruled out acute appendicitis. Four hours later, we observed a protrusion of the amniotic sac with the fetal head through a large uterine defect on magnetic resonance imaging, and performed emergency cesarean section. A boy was delivered without fetal compromise. During the cesarean section, multiple myometric wall defects and thinning were identified. After reconstruction of the uterine wall, the flaccid uterus bled persistently; thus, a cesarean hysterectomy was performed. Packed red cells and frozen plasma were transfused. The mother and neonate had uneventful puerperal and neonatal courses, respectively. After cesarean hysterectomy, we were informed that the mother had undergone a combined laparoscopic electromyolysis during the laparoscopic right ovarian cystectomy. Three years later, the child showed normal neural development. CONCLUSIONS: Before myomectomy or electromyolysis, patients should be informed of the possibility of uterine rupture during subsequent pregnancies. If a pregnant woman has abdominal pain, clinicians should take a detailed history of uterine surgery and consider uterine rupture. Although, fortunately, the outcomes in this case were uneventful, urgent delivery is required when uterine rupture is diagnosed.

Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia.

Castration-resistant prostate cancer (CRPC) is still a major concern in men's health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.