Menopausal Hormone Therapy and Osteoarthritis Risk: Retrospective Population-Based Study in South Korea.

OBJECTIVES: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). METHODS: This population-based retrospective cohort study used a database of Korean health insurance claims (2007-2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. RESULTS: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non-MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117-1.193) for knee (HR, 1.148; 95% CI, 1.102-1.195) and other arthritis (HR, 1.205; 95% CI, 1.151-1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161-1.263), estrogen-progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148-1.329) were associated with a higher risk of osteoarthritis compared to non-MHT users. CONCLUSIONS: MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis.

Impact of perioperative COVID-19 infection on postoperative complication in cesarean section using Korean National Health insurance data.

The vulnerability during pregnancy has raised concerns about the potential impact of COVID-19 on obstetric anesthesia, an essential aspect of maternal care during cesarean section procedures. To evaluate the influence of COVID-19 infection on obstetric anesthesia during cesarean section, we analyzed the data from Korean National Health Insurance System (NHIS). This retrospective study utilized data from Korean NHIS. We included patients admitted with operation codes specific to cesarean section between January 1, 2020, and December 31, 2021. We classified patients into a COVID (+) group with a diagnosis code (U071) 30 days around surgery and a COVID (-) group without the code in the same period. The primary outcome was 30-day mortality that was defined as death within 30 days of admission due to any causes. Secondary outcomes were pulmonary complications (pneumonia, acute respiratory distress syndrome [ARDS], pulmonary thromboembolism [PTE], or unexpected postoperative mechanical ventilation), ICU admission, cardiac arrest, myocardial infarction [MI], other thromboembolic events, surgical site infection, sepsis, acute renal failure [ARF], and hepatic failure. Among 75,268 patients who underwent cesarean section, 107 had a COVID-19 diagnosis code, while 75,161 did not. After 1:4 propensity score matching (PSM), 535 patients were included in each group. 30-day mortality showed no significant differences between the two groups both before and after PSM. The COVID (+) group demonstrated significantly elevated rates of pneumonia, ARDS, PTE, and surgical site infection both before and after PSM. Hospital length of stay and admission costs were also significantly longer and higher, respectively, in the COVID (+) group before and after PSM. In subgroup analysis, no differences were observed in mortality and postoperative complications based on the anesthesia method after matching. COVID-19 infection is associated with increased rates of postoperative complications, including pneumonia, ARDS, PTE, surgical site infection, longer hospital stays, and increased admission costs, in patients who underwent cesarean section.

Relationship between menopausal hormone therapy and colorectal cancer: a cohort study utilizing the health insurance database in South Korea (HISK)-II.

OBJECTIVE: Many studies have demonstrated that menopausal hormone therapy is associated with a reduced risk for colorectal cancer. This study investigated the relationship between specific hormone therapy regimens and colorectal cancer risk in postmenopausal women in South Korea using national insurance claims data. METHODS: This population-based, retrospective cohort study used insurance data provided by the Health Insurance Review and Assessment Service between 2007 and 2020. The hormone therapy group comprised women ≥40 years of age who underwent hormone therapy for the first time between 2011 and 2014. The control group included women ≥40 years of age who visited medical institutions for menopause-related issues during the same period but did not undergo hormone therapy. RESULTS: After 1:1 propensity score matching, 153,736 women were grouped into either the hormone therapy or nonhormone therapy groups. The incidence of colorectal cancer was 46 and 53 per 100,000 person-years in the nonhormone therapy and hormone therapy groups, respectively. Hormone therapy was associated with an increased risk for colorectal cancer (hazard ratio 1.124 [95% confidence interval 1.002-1.261]). Subgroup analysis, according to hormone therapy type, revealed no significant differences in the risk of colorectal cancer for estrogen plus progestogen or estrogen therapy alone; however, tibolone was associated with an increased risk of colorectal cancer compared to nonhormone therapy (hazard ratio, 1.178 [95% confidence interval, 1.021-1.359]). CONCLUSIONS: This study found an increased risk of colorectal cancer in women receiving hormone therapy, and tibolone was significantly associated with an increased risk of colorectal cancer. However, the magnitude of the increase was small and unlikely to be of clinical significance.

Enhanced Luminance of CdSe/ZnS Quantum Dots Light-Emitting Diodes Using ZnO-Oleic Acid/ZnO Quantum Dots Double Electron Transport Layer.

The widely used ZnO quantum dots (QDs) as an electron transport layer (ETL) in quantum dot light-emitting diodes (QLEDs) have one drawback. That the balancing of electrons and holes has not been effectively exploited due to the low hole blocking potential difference between the valence band (VB) (6.38 eV) of ZnO ETL and (6.3 eV) of CdSe/ZnS QDs. In this study, ZnO QDs chemically reacted with capping ligands of oleic acid (OA) to decrease the work function of 3.15 eV for ZnO QDs to 2.72~3.08 eV for the ZnO-OA QDs due to the charge transfer from ZnO to OA ligands and improve the efficiency for hole blocking as the VB was increased up to 7.22~7.23 eV. Compared to the QLEDs with a single ZnO QDs ETL, the ZnO-OA/ZnO QDs double ETLs optimize the energy level alignment between ZnO QDs and CdSe/ZnS QDs but also make the surface roughness of ZnO QDs smoother. The optimized glass/ITO/PEDOT:PSS/PVK//CdSe/ZnS//ZnO-OA/ZnO/Ag QLEDs enhances the maximum luminance by 5~9% and current efficiency by 16~35% over the QLEDs with a single ZnO QDs ETL, which can be explained in terms of trap-charge limited current (TCLC) and the Fowler-Nordheim (F-N) tunneling conduction mechanism.

Thin film encapsulation for quantum dot light-emitting diodes using a-SiN x :H/SiO x N y /hybrid SiO x barriers.

A facile thin film encapsulation (TFE) method having a triple-layered structure of a-SiN x :H/SiO x N y /hybrid SiO x (ASH) on QD-LEDs was performed utilizing both reproducible plasma-enhanced chemical vapor deposition (PECVD) and simple dip-coating processes without adopting atomic layer deposition (ALD). The ASH films fabricated on a polyethylene terephthalate (PET) substrate show a high average transmittance of 88.80% in the spectral range of 400-700 nm and a water vapor transmission rate (WVTR) value of 7.3 × 10-4 g per m2 per day. The measured time to reach 50% of the initial luminance (T50) at initial luminance values of 500, 1000, and 2000 cd m-2 was 711.6, 287.7, and 78.6 h, respectively, and the extrapolated T50 at 100 cd m-2 is estimated to be approximately 9804 h, which is comparable to that of the 12 112 h for glass lid-encapsulated QD-LEDs. This result demonstrates that TFE with the ASH films has the potential to overcome the conventional drawbacks of glass lid encapsulation.

Sarcopenia's Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: Although sarcopenia has been reported to predict survival in cancer patients, its impact on patients who received immune checkpoint inhibitors (ICIs) has not been thoroughly investigated. This systematic review aimed to assess the long-term oncologic impact of sarcopenia on patients who received ICIs. METHODS: A systematic review of studies indexed in the PubMed, Embase, and Cochrane databases, up to April 1, 2021, was conducted. Studies that reported hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) based on sarcopenia in patients treated with ICIs were included. The inverse variance method was used with a random-effects model for data analysis. RESULTS: A total of 1284 patients from 14 studies were included. Among the patients who received ICIs, patients with sarcopenia had a significant increase in overall mortality compared to patients without sarcopenia in univariate analyses (HR = 1.66, 95% CI = 1.20-2.29, p = 0.002) and in adjusted HRs (HR = 1.55, 95% CI = 1.15-2.10, p = 0.004). The same results were obtained for PFS by both univariate analysis (HR = 1.75, 95% CI = 1.37-2.23, p < 0.001) and adjusted HRs (HR = 1.63, 95% CI 1.28-2.09, p < 0.001). CONCLUSIONS: Sarcopenia appears to be an effective biomarker for predicting long-term oncologic outcomes in patients receiving ICI therapy and hence plays an important role when making treatment decisions. However, the fundamental role of this association with survival should be further investigated in large cohorts and clinical trials.

Cecal malakoplakia: A case report.

Malakoplakia is a rare chronic granulomatous disease found in the genitourinary tract, mainly. It is considered to be related to immunosuppression and/or infectious processes. We would like to present an operative case of cecal malakoplakia in a patient with a history of surgical resection and chemotherapy for cervical cancer. A 74-year-old female patient visited our hospital for 1-year follow-up after operation and chemo-radiotherapy for cervical cancer. An infiltrative mass of 6 cm, between the cecal base and the right psoas muscle, was observed on computed tomography. An ileocectomy was performed for diagnosis. Histopathologic examination revealed cecal malakoplakia. After surgery, based on previous reports, antibiotics therapy was added. Then the patient was discharged and treated in the outpatient clinic. To our knowledge, a rare case has been described of cecal malakoplakia during observation after surgery and chemo-radiotherapy for cervical cancer. Malakoplakia is known to be related to immunosuppressive condition. Therefore, our case suggests that close observation should be made in patients on immunosuppressive condition, such as chemotherapy.

Older menarche age and short reproductive period linked to chronic kidney disease risk.

This study aimed to investigate the association between reproductive period and menarche age and chronic kidney disease (CKD) in South Korean postmenopausal women.This was a cross-sectional study of the data for 8510 postmenopausal women using the results of Korean National Health and Nutrition Examination Surveys over the past 6 years.Of the total 8510 postmenopausal women, 790 (10.23%) were CKD patients. The menarche age in the CKD group was 16.2 ±â€Š1.9 years old, which was higher than that in the non-CKD group (P < .001). The reproductive period of the CKD group was 32.4 ±â€Š5.7 years, which was shorter than 33.3 ±â€Š5.4 years in the non-CKD group (P < .001). The prevalence of CKD was 4.7% at a menarche age of 11 years or younger, which increased with increasing of menarche age, reaching 9.9% at menarche age of 16 years or older. According to the length of the reproductive period, the prevalence of CKD was 13.9% for the group less than 20 years of period and decreased significantly with increasing length of reproductive period. The prevalence of proteinuria was 7.2% in women with reproductive period of less than 20 years and significantly less in women with a reproductive period longer than 45 years (2.3%). The prevalence of CKD and proteinuria increased with increasing of menarche age, and the prevalence of CKD and proteinuria decreased with increasing of reproductive period.The results suggest that CKD was associated with older menarche age and a short reproductive period. Management of life patterns and medical problems in women with old age at menarche and a short reproductive period should be considered.

Prognostic factors after hepatic resection for the single hepatocellular carcinoma larger than 5 cm.

PURPOSE: This study aimed to determine which factors affect the prognosis of hepatectomy for hepatocellular carcinoma (HCC) larger than 5 cm, including the prognostic difference between tumor sizes from 5-10 cm and larger than 10 cm. METHODS: The medical records of 114 patients who underwent hepatectomy for single HCC larger than 5 cm were reviewed and analyzed retrospectively. RESULTS: In the analysis of the entire cohort of 114 patients, the 5-year overall and diseases-free survival rates were 50% and 29%, respectively. In a comparison of survival rates between groups, tumor sizes of 5 to 10 cm and larger than 10 cm, the overall and disease-free survival rates were not significantly different, respectively (54% vs. 41%, P = 0.433 and 33% vs. 23%, P = 0.083). On multivariate analysis, positive hepatitis B, high prothrombin induced by vitamin K absence or antagonist-II levels over 200 mIU/mL, and vascular invasion (micro- and macrovascular invasion) were independent prognostic factors for recurrence after hepatic resection. However, tumor size larger than 10 cm was not significant for recurrence after resection. CONCLUSION: This study shows that surgical resection of solitary HCC larger than 5 cm showed favorable overall survival. And there is no survival difference with tumors between 5-10 cm and larger than 10 cm.

Aerobic Oxidative Conversion of Aromatic Aldehydes to Nitriles Using a Nitroxyl/NOx Catalyst System.

The first transition-metal-free aerobic oxidative conversion of aldehyde catalyzed by a nitroxyl radical/NOx system is presented for the synthesis of nitrile. In the presence of a catalytic amount of 4-AcNH-TEMPO (4-acetamido-2,2,6,6-tetramethylpiperidine-N-oxyl), NaNO2, and HNO3, benzaldehydes bearing a variety of functional groups underwent condensation with NH4OAc and following aerobic oxidation to produce nitriles selectively under an O2 balloon. Aerobic oxidative conversion of a primary alcohol instead of aldehyde is also achieved by a one-pot sequential strategy.

Leiomyomatosis peritonealis disseminata associated with appendiceal endometriosis: a case report.

INTRODUCTION: Leiomyomatosis peritonealis disseminata is a very rare benign condition of the peritoneal cavity that may mimic peritoneal carcinomatosis or metastatic leiomyosarcomas. It mainly develops in association with pregnancy, but is also rarely associated with endometriosis. CASE PRESENTATION: A 31-year-old Asian woman presented to our hospital with abdominal pain in the right lower quadrant. Her abdominopelvic computed tomography scan showed a 1.2cm-sized nodule at the appendiceal tip, but no other abnormal findings. We suspected acute appendicitis and performed an exploratory laparoscopy. Her appendix was enlarged at the tip portion. Also noted were blood-colored fluid collections in her pelvic cavity and bilateral ovarian cysts. Additionally, several small whitish firm solid nodules, ranging from 0.5 to 1.0cm in size, were present on her pelvic peritoneum. Her histological examination confirmed that the endometriosis of her appendix coexisted with leiomyomatosis peritonealis disseminata. CONCLUSIONS: We report a case involving a 31-year-old woman with acute symptoms of endometriosis of the appendix associated with leiomyomatosis peritonealis disseminata. Appendiceal endometriosis with leiomyomatosis peritonealis disseminata presenting as acute appendicitis is extremely rare. To the best of our knowledge, this is the first such case reported in the literature.

Mesenteric desmoid-type fibromatosis causing secondary hypertension in a young woman.

This report describes an 18-year-old woman presenting with abdominal distension, left flank pain, and hypertension. She had a huge abdominal mass, diagnosed as a mesenteric desmoid-type fibromatosis, causing compression of the left external iliac vessels and ureter, as well as elevated renin concentration and hypertension. After surgical removal of the mass, all signs improved including hypertension.

Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors.

Extracellular ATP has recently been identified as an important regulator of cell death in response to pathological insults. When SN4741 cells, which are dopaminergic neurons derived from the substantia nigra of transgenic mouse embryos, are exposed to ATP, cell death occurs. This cell death is associated with prominent cell swelling, loss of ER integrity, the formation of many large cytoplasmic vacuoles, and subsequent cytolysis and DNA release. In addition, the cleavage of caspase-3, a hallmark of apoptosis, is induced by ATP treatment. However, caspase inhibitors do not overcome ATP-induced cell death, indicating that both necrosis and apoptosis are associated with ATP-induced cell death and suggesting that a necrotic event might override the apoptotic process. In this study we also found that P2X(7) receptors (P2X(7)Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X(7)Rs antagonist, KN62, or by knock-down of P2X(7)Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X(7)Rs.

Marked prevention of ischemic brain injury by Neu2000, an NMDA antagonist and antioxidant derived from aspirin and sulfasalazine.

Excitotoxicity and oxidative stress mediate neuronal death after hypoxic-ischemic brain injury. We examined the possibility that targeting both N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity and oxidative stress would result in enhanced neuroprotection against hypoxic-ischemia. 2-Hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000) was derived from aspirin and sulfasalazine to prevent both NMDA neurotoxicity and oxidative stress. In cortical cell cultures, Neu2000 was shown to be an uncompetitive NMDA receptor antagonist and completely blocked free radical toxicity at doses as low as 0.3 micromol/L. Neu2000 showed marked neuroprotection in a masked fashion using histology and behavioral testing in two rodent models of focal cerebral ischemia without causing neurotoxic side effects. Neu2000 protected against the effects of middle cerebral artery occlusion, even when delivered 8 h after reperfusion. Single bolus administration of the drug prevented gray and white matter degeneration and spared neurologic function for over 28 days after MACO. Neu2000 may be a novel therapy for combating both NMDA receptor-mediated excitotoxicity and oxidative stress, the two major routes of neuronal death in ischemia, offering profound neuroprotection and an extended therapeutic window.

The effect of Vero cell coculture on the development of mouse embryos exposed to monoclonal antibodies specific for mammalian heat shock protein 60.

Heat shock proteins (HSP) have been identified as an important factor of a very complex and highly conserved cellular defense mechanism to preserve cell survival under adverse environmental conditions. HSP 60 are immunodominant antigens of microbe such as Chlamydia trachomatis and have a potentiality to become a target antigen due to antigenic similarity between chlamydial and human HSP. This study was conducted to investigate the effects of Vero cell coculture to anti-HSP 60 on the early mouse embryo development in vitro. The 2-cell mouse embryos (ICR) were cultured and mouse embryo development was observed every 24 hr for 3 days. 45% and 22.1% of the embryos cultured in Ham's F-10 plus anti HSP 60 with Vero cells developed to the 4- to 8- cell stage (day 1) and morular stage (day 2) as compared with 29.2% and 2.7% of those cultured without Vero cells respectively. But at day 3, the beneficial effect of Vero cells was not noted. These findings suggest that Vero cells have some roles to overcome the detrimental effect of anti-HSP 60 to some degree. These results suggest that Vero cells coculture will promote reproductive outcome in patient previously sensitized to microbial (e.g. Chlamydia trachomatis) HSP 60.

No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population.

BACKGROUND: The aetiological factors of endometriosis still remain poorly understood. While there is growing evidence that genetic and immunological factors play important roles in the pathogenesis of the disease, HLA-DRB1 alleles have been reported to be associated with the risk of endometriosis in Japanese populations. This study was performed to determine whether susceptibility to advanced endometriosis is also associated with HLA-DRB1 alleles in a Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 100 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. HLA-DRB1 genotyping was carried out in two steps. Low to intermediate resolution typing was performed by PCR sequence-specific oligonucleotide hybridization method, followed by high resolution typing utilizing group-specific amplification and PCR-single strand conformation polymorphism method. Distribution of HLA-DRB1 alleles was compared with that of 800 unrelated ethnically matched individuals as well as 108 healthy female subjects. RESULTS: Genotyping revealed that the distribution of HLA-DRB1 alleles in patients with advanced endometriosis was not different from that in the two control groups. CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population.

Underlying mechanism for NMDA receptor antagonism by the anti-inflammatory drug, sulfasalazine, in mouse cortical neurons.

Sulfasalazine (SULFA), of anti-inflammatory drugs, shows a protective action against NMDA-induced neuronal toxicity. Here, we used an electrophysiological study of the pharmacological effects of SULFA on NMDA receptors to examine the molecular mechanisms underlying the neuroprotective role of SULFA. The drug acted as a typical noncompetitive inhibitor with neither agonist- nor use-dependency, and antagonized NMDA-evoked responses in a voltage-independent manner, suggesting that SULFA is not an open channel blocker. Noise and single channel analyses showed that SULFA-blocked NMDA responses by reducing the number of NMDA channels available for activation, and also reduced the channel open probability without changing single channel conductance. Moreover, SULFA accelerated NMDA desensitization without affecting the affinity of the receptor for NMDA or glutamate. Taken together, these data indicate that SULFA blocks the NMDA response by reducing the number of NMDA channels available for activation. This appears to occur via a SULFA-induced decrease in the channel open probability, and a concomitant acceleration of the desensitization response, which is likely associated with a reduced affinity for glycine. SULFA indeed decreased the glycine-potentiated NMDA response without binding directly to the glycine site. Our results suggest that SULFA acts as a noncompetitive NMDA receptor antagonist with an allosteric glycine modulation.

Zinc reduces low-threshold Ca2+ currents of rat thalamic relay neurons.

Whole-cell voltage-clamping of thalamic relay neurons was used to examine the possibility of a Zn(2+)-mediated reduction of the low-threshold transient Ca(2+) current (I(T)) of a central element in thalamocortical oscillations. We found that Zn(2+) reversibly decreased I(T) in a concentration-dependent manner (IC(50)=55 microM), mainly by reducing the number of I(T) channels available for activation. Zn(2+) did not affect the reaction kinetics, but did affect the voltage-dependence of I(T) channel gating. However, the apparent alterations in gating properties were not enough to account for the huge I(T) reduction.

The novel neuroprotective action of sulfasalazine through blockade of NMDA receptors.

Sulfasalazine is widely used to treat inflammatory diseases. Besides anti-inflammatory actions such as blockade of nuclear factor-kappaB and cyclooxygenases, we found that 30 to 1000 micro M sulfasalazine dose dependently blocked N-methyl-D-aspartate receptor-mediated excitotoxicity without intervening kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid neurotoxicity. The neuroprotective effects of sulfasalazine were attributable to prevention of Ca(2+) influx and accumulation through N-methyl-D-aspartate receptors as a low-affinity antagonist. The systemic administration of sulfasalazine reduced neuronal death following transient cerebral and retinal ischemia in adult rat. The present findings suggest that the neuroprotective action of sulfasalazine can be therapeutically applied to halt devastating neuronal death following hypoxic ischemia, trauma, and neurodegenerative diseases.