Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Background/Aims: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. Methods: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. Results: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of “PPI and H2RA” (HR, 1.58; p = 0.010) as well as “PPI, H2RA, and MPA” (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, “MPA and PPI or H2RA” was not associated with an increased risk of osteoporotic fracture. Conclusions This study found that the combined use of “PPI and H2RA” was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Background/Aims: Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). Methods: An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Results: Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Conclusions Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Purpose: We report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) to treat graft failure after Descemet stripping endothelial keratoplasty (DSEK).Case summary: A 66-year-old female underwent DSEK of her right eye to treat pseudophakic bullous keratopathy that developed after cataract surgery and intraocular lens exchange. After 5 years, she complained of decreased vision; graft failure was observed. Secondary DMEK was performed; no additional air injection was needed. The corrected visual acuity was 0.2, 3 months after surgery, and the cornea became clear. Conclusions Visual recovery can be achieved by performing secondary DMEK after primary DSEK graft failure.

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a novel Phlebovirus, is endemic to South Korea, central and northeastern China, and western Japan. SFTS poses a threat to public health because of its high mortality and secondary transmission. Ticks and domestic animals are hosts for SFTSV in endemic areas. There is no specific treatment for SFTS, and avoiding tick bites is the best way to prevent infection. Early therapeutic plasma exchange (TPE) is a rescue therapy in patients with rapidly progressive SFTS. Here, we present a patient with SFTS who was improving on TPE but died suddenly due to acute lung injury after TPE.

Purpose: We report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) to treat graft failure after Descemet stripping endothelial keratoplasty (DSEK).Case summary: A 66-year-old female underwent DSEK of her right eye to treat pseudophakic bullous keratopathy that developed after cataract surgery and intraocular lens exchange. After 5 years, she complained of decreased vision; graft failure was observed. Secondary DMEK was performed; no additional air injection was needed. The corrected visual acuity was 0.2, 3 months after surgery, and the cornea became clear. Conclusions Visual recovery can be achieved by performing secondary DMEK after primary DSEK graft failure.

Purpose: This study aimed to evaluate real-world clinical outcomes from surgically treated patients for sigmoid volvulus. Methods: Five tertiary centers participated in this retrospective study with data collected from October 2003 through September 2018, including demographic information, preoperative clinical data, and information on laparoscopic/open and elective/emergency procedures. Outcome measurements included operation time, postoperative hospitalization, and postoperative morbidity. Results: Among 74 patients, sigmoidectomy was the most common procedure (n = 46), followed by Hartmann’s procedure (n = 23), and subtotal colectomy (n = 5). Emergency surgery was performed in 35 cases (47.3%). Of the 35 emergency patients, 34 cases (97.1%) underwent open surgery, and a stoma was established for 26 patients (74.3%). Elective surgery was performed in 39 cases (52.7%), including 21 open procedures (53.8%), and 18 laparoscopic surgeries (46.2%). Median laparoscopic operation time was 180 minutes, while median open surgery time was 130 minutes (P < 0.001). Median postoperative hospitalization was 11 days for laparoscopy and 12 days for open surgery. There were 20 postoperative complications (27.0%), and all were resolved with conservative management. Emergency surgery cases had a higher complication rate than elective surgery cases (40.0% vs. 15.4%, P = 0.034). Conclusion Relative to elective surgery, emergency surgery had a higher rate of postoperative complications, open surgery, and stoma formation. As such, elective laparoscopic surgery after successful sigmoidoscopic decompression may be the optimal clinical option.

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Blood Glucose ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Metformin ; Weight Loss

BACKGROUND/AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever with a high fatality rate. However, effective treatments for SFTS cases not responded to supportive therapy have not been established. Herein, we introduced the therapeutic plasma exchange (TPE) in SFTS patients in a tertiary hospital between 2013 and 2015. METHODS: TPE was performed in patients with rapidly progressing SFTS. Clinical, laboratory, and virological parameters were compared before and after TPE. RESULTS: Among 27 confirmed SFTS patients, two patients were treated with TPE and ribavirin combination in May 2013, then, 14 patients with rapidly progressing SFTS patients were treated with only TPE from June 2013 to September 2015: their median age was 58 years (interquartile range, 50 to 70) and eight (57.1%) were male. Body temperature, pressure-adjusted heart rate, white blood cell and platelet counts, coagulation profile, serum creatinine, and multiple organ dysfunction score improved immediately after TPE. In addition, the mean cyclic threshold value of real-time reverse transcriptase polymerase chain reaction for SFTS virus after TPE (mean ± standard deviation, 31.3 ± 2.9) was significantly higher than that before TPE (26.5 ± 2.9; p < 0.001), indicating that serum viral loads decreased after TPE. Finally, 13 of 14 TPE-treated patients (92.8%) recovered from rapidly progressing SFTS without sequelae. CONCLUSIONS SFTS patients treated with TPE showed improvements in clinical, laboratory, and virological parameters. These results suggest that TPE would be a therapeutic modality as rescue therapy in patients with rapidly progressing SFTS.

Pancreatic neoplasm is complicated and can be preceded by extra-pancreatic manifestations, such as cutaneous and musculoskeletal symptoms. Awareness of these associations is important for timely diagnosis and appropriate treatment. We report a case of pancreatic neuroendocrine tumor (NET) presenting with arthritis and panniculitis. The patient had a two month history of right knee pain and subcutaneous nodules in both legs. Synovial fluid analysis from the right knee joint revealed a mildly increased white blood cell count without crystallization. A skin biopsy of a subcutaneous nodule revealed lobular panniculitis. The initial treatment with empirical antibiotics did not alleviate the symptoms; however, the right knee arthritis and skin nodules improved with steroid treatment. On the eighth day of hospitalization, the patient complained of abdominal discomfort. Abdominopelvic computed tomography scanning revealed a 14-cm sized pancreatic mass with peritoneal metastasis. Percutaneous needle biopsy confirmed the diagnosis of pancreatic NET.
Anti-Bacterial Agents ; Arthritis* ; Biopsy ; Biopsy, Needle ; Crystallization ; Diagnosis ; Hospitalization ; Humans ; Knee ; Knee Joint ; Leg ; Leukocyte Count ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreatic Neoplasms ; Panniculitis* ; Skin ; Synovial Fluid