Survival Benefit for Metformin Through Better Tumor Response by Neoadjuvant Concurrent Chemoradiotherapy in Rectal Cancer.

BACKGROUND: Metformin may reduce cancer risk and mortality and improve radiotherapy responses in several malignancies. OBJECTIVE: This study aimed to compare tumor responses and prognoses of metformin and nonmetformin groups of diabetic patients receiving neoadjuvant concurrent chemoradiotherapy for rectal cancer. DESIGN: This is a retrospective study. SETTING: This study was conducted at a single institution in the Republic of Korea. PATIENTS: Between January 2000 and November 2017, 104 patients with rectal cancer who were taking diabetes medication and treated with neoadjuvant concurrent chemoradiotherapy followed by radical surgery were reviewed. Patients were divided into those taking (n = 62) and not taking metformin (n = 42). Tumor responses, survival, and other outcomes were analyzed. MAIN OUTCOME MEASURES: Tumor response, rectal cancer-specific survival, and disease-free survival rates were measured. RESULTS: Tumor regression grade (p = 0.002), pathological complete response (p = 0.037), and N downstaging (p < 0.001) after neoadjuvant concurrent chemoradiotherapy were significantly higher in the metformin group than in the nonmetformin group. In analysis of cancer-specific mortality, metformin use, differentiation (well, moderate vs poor), pathological Union for International Cancer Control stage (3 vs 1-2), ypN stage (1-2 vs 0), and N downstaging (HR, 0.256 (95% CI, 0.082-0.794), p = 0.018; HR, 0.147 (95% CI, 0.031-0.697), p = 0.016; HR, 3.693 (95% CI, 1.283-10.635), p = 0.015; HR, 3.181 (95% CI, 1.155-8.759), p = 0.025, and HR, 0.175 (95% CI, 0.040-0.769), p = 0.021) were significant factors related to mortality in diabetic patients with rectal cancer. In addition, in the multivariate analysis of cancer recurrence, the interaction between metformin use and lymph node downstaging was a significant predictive factor (HR, 0.222 (95% CI, 0.077-0.639); p = 0.005). LIMITATIONS: This was a small retrospective study conducted at a single institution. CONCLUSIONS: Metformin use was associated with better tumor responses and cancer-specific survival, as well as a lower risk of cancer recurrence, in patients with diabetes mellitus who had lymph node downstaging after neoadjuvant concurrent chemoradiotherapy in rectal cancer. See Video Abstract at http://links.lww.com/DCR/B185. BENEFICIO EN SUPERVIVENCIA CON METFORMINA A TRAVÉS DE UNA MEJOR RESPUESTA TUMORAL CON QUIMIORRADIOTERAPIA CONCURRENTE NEOADYUVANTE EN CÁNCER RECTAL: La metformina puede reducir el riesgo de cáncer y la mortalidad y mejorar las respuestas a la radioterapia en varios tumores malignos.Comparar las respuestas tumorales y los pronósticos de los grupos con metformina y sin metformina de pacientes diabéticos que reciben quimiorradioterapia concurrente neoadyuvante para cáncer de recto.Estudio retrospectivo.Institución única en la República de Corea.Se revisaron 104 pacientes entre enero de 2000 y noviembre de 2017, con cáncer rectal que tomaban medicamentos para diabetes y que fueron tratados con quimiorradioterapia concurrente neoadyuvante seguida de cirugía radical. Los pacientes se dividieron en aquellos que tomaban (n = 62) y los que no tomaban metformina (n = 42). Se analizaron las respuestas tumorales, la supervivencia y otros resultados.Se midieron las tasas de la respuesta tumoral, la supervivencia específica de cáncer rectal y de la supervivencia libre de enfermedad.El grado de regresión tumoral (p = 0.002), la remisión patológica completa (p = 0.037) y la reducción de la etapa N (p < 0.001) después de la quimiorradioterapia concurrente neoadyuvante fueron significativamente mayores en el grupo de metformina que en el grupo sin metformina. En el análisis de la mortalidad específica por cáncer, el uso de metformina, la diferenciación (bien, moderada vs pobre), el estadio patológico UICC (3 vs 1-2), el estadio ypN (1-2 vs 0) y la disminución de la etapa N (hazard ratios [intervalos de confianza 95%]: 0.256 [0.082-0.794], p = 0.018; 0.147 [0.031-0.697], p = 0.016; 3.693 [1.283-10.635], p = 0.015; 3.181 [1.155-8.759], p = 0.025 y 0.175 [0.040-0.769], p = 0.021, respectivamente) fueron factores significativos relacionados con la mortalidad en pacientes diabéticos con cáncer rectal. Adicionalmente, en el análisis multivariado de la recurrencia del cáncer, la interacción entre el uso de metformina y la disminución de la etapa ganglionar (N) fue un factor predictivo significativo (hazard ratios [intervalos de confianza del 95%]: 0.222 [0.077-0.639]; p = 0.005).Este fue un estudio retrospectivo pequeño realizado en un solo instituto.El uso de metformina se asoció con mejores respuestas tumorales y supervivencia específica de cáncer, así como un menor riesgo de recurrencia del cáncer, en pacientes con disminución de la etapa ganglionar (N) después de quimiorradioterapia concurrente neoadyuvante en pacientes con cáncer rectal y diabetes. Consulte Video Resumen en http://links.lww.com/DCR/B185. (Traducción-Dr. Jorge Silva Velazco).

Molecular Drug Discovery of Single Ginsenoside Compounds as a Potent Bruton's Tyrosine Kinase Inhibitor.

: Bruton's tyrosine kinase (BTK) is known as a direct regulator of inflammasome, which is an intracellular target to therapeutically modulate innate immunity. Although there is great interest in developing small molecule-based drugs with BTK inhibition, there are only a few drugs available in the market, due to the difficulty of drug discovery and the potential side effects. To select suitable drug compounds to inhibit BTK signaling, molecular drug screening bioassay processes of single ginsenosides integrated with in silico molecular simulation were performed. The experimental results for the ginsenoside compositions (Rb2 and Rb3) exhibited showed that they effectively suppressed the activity of BTK expression in a rational agreement with molecular docking calculations of the compounds against the BTK binding site. They implemented a possible inhibiting effect of BTK signaling through increasing their molecular affinity for targeting BTK, enabling them to be useful in treating BTK-mediated diseases.

Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress.

BACKGROUND AND AIM: Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects, and we investigated their mechanisms related to NF-κB and ER-stress pathways. METHODS: Luciferase, nitric oxide, and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse-transcription polymerase chain reaction. RESULTS: Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium-treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro-inflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo. CONCLUSIONS: We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased ß-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Ulmus macrocarpa Hance Extracts Attenuated H2O2 and UVB-Induced Skin Photo-Aging by Activating Antioxidant Enzymes and Inhibiting MAPK Pathways.

To protect from reactive oxygen species (ROS) damages, skin cells have evolved to have antioxidant enzymes, such as copper and zinc-dependent superoxide dismutase (SOD1), mitochondrial manganese-dependent superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR), and suppressed the expression of matrix metalloproteinases (MMPs) through the mitogen-activated protein kinase (MAPK) signaling pathways, such as c-Jun N-terminal kinase (JNK) and p38. Bioactive compounds analyses were performed using a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) system. The antioxidant activity of Ulmus macrocarpa Hance (UMH) extracts was estimated in vitro. The anti-aging activity of UMH extracts was estimated in vivo using the SKH-1 hairless mice. The UMH extracts reduced the H2O2-induced intracellular ROS production and the cell damages in human dermal fibroblasts (HDFs). Moreover, the H2O2-induced phosphorylation of JNK and p38 was detected in HDF and UMH extracts blocked the phosphorylation. These results suggest that UMH extracts can reduce the expression of MMPs and the reduced MMPs lead to the inhibition of collagen degradation. In addition, oral administration of the UMH extracts decreased the depth, thickness, and length of wrinkles on UVB exposed hairless mice. Therefore, UMH extracts play an advantage of the functional materials in antioxidant and anti-aging of skin.

Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats.

Seasonal Variation in Flares of Intestinal Behçet's Disease.

BACKGROUND: There have been numerous investigations into the seasonality of several autoimmune diseases and inflammatory bowel disease in an effort to better understand the epidemiology and pathogenesis of these conditions. However, the relationship between the season and disease activity of intestinal Behçet's disease has not been investigated. AIMS: This study aimed to evaluate the seasonal pattern of exacerbations of intestinal Behçet's disease. METHODS: We evaluated 268 consecutive patients with intestinal Behçet's disease who were diagnosed and treated between November 1990 and March 2010 at Severance Hospital, Yonsei University, Seoul, Korea. Patient demographics, onset of symptoms, total number of relapses, and the month of each relapse were recorded. The relationship between the season and flares of intestinal Behçet's disease was analyzed. RESULTS: A total of 339 relapses occurred in 142 patients (53 %). The median age at diagnosis was 39 (10-73) years; the median follow-up duration was 74 (7-372) months. The peak seasons for relapse were spring and autumn, especially the months of May and September (p value <0.001). Compared with winter, spring and autumn had higher rates of flares (HR 1.92 and 1.91, respectively, p value <0.001). CONCLUSIONS: In this study, intestinal Behçet's disease demonstrated a biphasic pattern (peaks in spring and autumn) in exacerbations of disease, suggesting that seasonal or exogenous factors may be involved in the flares of intestinal Behçet's disease.

Acute and subchronic (28 days) oral toxicity studies of Codonopsis lanceolata extract in Sprague-Dawley rats.

Codonopsis lanceolata is a perennial plant that has been used as a food and in traditional medicine for the treatment of cough, bronchitis, and inflammation in East Asia including Korea, Japan, and China. However, information regarding its toxicity is limited. Therefore, we performed a safety evaluation of aqueous C. lanceolata root extract (CLE) in Sprague-Dawley rats. Assessment of acute toxicity revealed that CLE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 5000 mg/kg body weight. In the subchronic oral toxicity, data revealed that several significant alteration in food consumption, water consumption, protein excretion, WBCs levels, TGs, BUN levels, and the absolute and relative weights in the liver, spleen and lungs. However, these changes were transient and were not considered treatment related because they showed no apparent dose dependent. These results suggest that CLE (1250, 2500, and 5000 mg/kg body weight/day) administered orally does not cause acute or subchronic toxicity to male or female rats. The 50% lethal dose (LD50) of CLE was determined to be greater than 5000 mg/kg.

The antioxidant activity and their major antioxidant compounds from Acanthopanax senticosus and A. koreanum.

The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid were validated by HPLC chromatography. Among the various extracts, the fruit extracts of A. senticosus and A. koreanum exhibited strongest antioxidant activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH radical scavenging activity was observed from the leaf extract of A. senticosus. In addition, the antioxidant activities of various extracts were correlated with total phenolic and proanthocyanidin contents. The major phenolic contents from various parts of these plants observed that leaf extract of A. senticosus expressed higher levels of chlorogenic acid (14.86 mg/dry weigh g) and caffeic acid (3.09 mg/dry weigh g) than other parts. Therefore, these results suggest that the leaf of A. senticosus may be an excellent natural source for functional foods and pharmaceutical agents, and the validated method was useful for the quality control of A. senticosus.

Surveillance strategy for rectal neuroendocrine tumors according to recurrence risk stratification.

BACKGROUND/AIM: Rectal neuroendocrine tumors (NETs) have been increasing in incidence. However, the recommendations for disease surveillance after tumor resection have not been well established. We evaluated the long-term outcomes of rectal NETs and surveillance strategies according to recurrence risk stratification. METHODS: From January 2000 to July 2011, 188 patients diagnosed with rectal NETs were included in this study. Patient characteristics, treatment methods, recurrence rates, risk factors of recurrence, and surveillance schedules were analyzed. RESULTS: The male-to-female ratio was 1.29:1 and the mean age at diagnosis was 50.6 years. The mean tumor size was 6.5 (range 1-30) mm. A total of 144 patients (76.6 %) were treated with endoscopic resection, and 44 patients (23.4 %) were treated with surgical resection as the initial treatment. During the follow-up period, ten patients (5.3 %) had disease recurrence, including one case of local recurrence and nine cases of recurrence at a distant site. Tumor size of >10 mm, invasion of the muscularis propria, increased mitotic index, lymphovascular invasion, and regional lymph node metastases were statistically significant predictors of recurrence by univariate analysis. Among the 152 patients without risk factors of recurrence, only one patient who underwent transanal resection had a local recurrence at 15 months after surgery. CONCLUSION: Our patients with rectal NETs showed favorable clinical outcomes and had a low rate of recurrence. Intensive surveillance with endoscopy or imaging study may not be required in patients without risk factors for recurrence.

Audience reconstructed: social media interaction by BTS fans during live stream concerts.

COVID-19-motivated social distancing made online concerts common practice in 2020 and 2021, with millions logging into streaming sites to see their favorite artists perform in realtime. For some fans, watching alone at home may have been enough, but concert-concurrent surges of social media activity suggest many virtual performance attendees are doing more. To understand why fans would turn their attention from these precious performance streams to social media, we explored Twitter engagement during four live streamed concerts performed by the Kpop group BTS in 2021. In public Tweets sampled by either concert hashtag or a predefined stream of users and keywords, we evaluated patterns in posting rates in relation to concert program events and investigated the content patterns in 1,200 Tweets sampled from four ranges of popularity (number of Retweets during the concert). Across concerts, short "Shout" Tweets surged at the start of songs, while the rate of retweets often fell during musical performances and shot up when BTS was off stage. Content analysis on the subsample found the materials most widely shared were informational or featured concert visuals, mimicking how fans use their phones at in-person concerts. Most original posts received few Retweets and were more personal and expressive of admiration for the performers. Comparison between the samples (concert hashtag vs. stream) also suggests users were strategic in using or omitting official concert hashtags with the strongest differences in the most widely disseminated content. Postings on Twitter during these performances seemed principally directed to fellow fans and audience members, by individuals choosing to share their own excitement and check in with others. By leveraging their existing social media networks, these concert attendees constructed a collective and interactive concert space, connecting with friends and strangers in the crowd and helping each other capture a richer experience than any broadcasting platform currently supports.

CoCl2 induces apoptosis through the mitochondria- and death receptor-mediated pathway in the mouse embryonic stem cells.

Embryonic hypoxia/ischemia is a major cause of a poor fetal outcome and future neonatal and adult handicaps. However, biochemical cellular events in mouse embryonic stem (mES) cells during hypoxia remains unclear. This study investigated the underlying mechanism of apoptosis in mES cells under CoCl2-induced hypoxic/ischemic conditions. CoCl2 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and the accumulation of reactive oxygen species in mES cells. The CoCl2-treated mES cells showed a decrease in cell viability as well as typical apoptotic changes, cell shrinkage, chromatin condensation, and nuclear fragmentation and an extended G2/M phase of the cell cycle. CoCl2 augmented the release of cytochrome c into the cytosol from the mitochondria with a concomitant loss of the mitochondrial transmembrane potential (ΔΨm) and upregulated the voltage-dependent anion channel. In addition, CoCl2-induced caspase-3, -8, and -9 activation and upregulation of p53 level, whereas downregulated Bcl-2 and Bcl-xL, a member of the anti-apoptotic Bcl-2 family in mES cells. Furthermore, CoCl2 led to the upregulation of Fas and Fas-ligand, which are the death receptor assemblies, as well as the cleavage of Bid in mES cells. These results suggest that CoCl2 induces apoptosis through both mitochondria- and death receptor-mediated pathways that are regulated by the Bcl-2 family in mES cells.

The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus.

Metformin use has been associated with decreased cancer risk and mortality. However, the effects of metformin on clinical outcomes of colorectal cancer (CRC) are not defined. This study aimed to evaluate the association between metformin use and mortality of CRC in diabetic patients. We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin. Patient's demographics, clinical characteristics, overall mortality and CRC-specific mortality were analyzed. After a median follow-up of 41 months, there were 71 total deaths (27.5%) and 55 CRC-specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC-specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (p = 0.018) and CRC-specific mortality (p = 0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 0.66; 95% CI 0.476-0.923; p = 0.015) and CRC-specific mortality (HR, 0.66; 95% CI 0.45-0.975; p = 0.037) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC-specific and overall mortality.

The role of capsule endoscopy after negative CT enterography in patients with obscure gastrointestinal bleeding.

OBJECTIVES: The aim of the present study was to evaluate the role of capsule endoscopy in patients with obscure gastrointestinal bleeding (OGIB) after negative computed tomographic (CT) enterography. METHODS: We retrospectively included 30 patients with OGIB who received capsule endoscopy after negative CT enterography. The median age of the patients was 60 years, and 60% of patients were male. The median follow-up duration was 8 months. Overt bleeding was 60%, and occult bleeding was 40%. RESULTS: Based on capsule endoscopy results, a definitive diagnosis was made for 17 patients (57%): ulcer in nine patients (30%), active bleeding with no identifiable cause in five (17%), angiodysplasia in two (7%) and Dieulafoy's lesion in one (3%). Two patients with jejunal ulcers were diagnosed with Crohn's disease. Seven patients (41%) with positive capsule endoscopy received double balloon enteroscopy and two patients (12%) received steroid treatment for Crohn's disease. Patients with overt bleeding, a previous history of bleeding, or who received large amounts of blood transfusions were more likely to show positive capsule endoscopy. CONCLUSIONS: Capsule endoscopy showed high diagnostic yields in patients with OGIB after negative CT enterography and may help to provide further therapeutic plans for patients with OGIB and negative CT enterography. KEY POINTS: • CT enterography has been widely used in evaluating obscure gastrointestinal bleeding (OGIB). • Capsule endoscopy showed high diagnostic yield for OGIB after negative CT enterography. • Negative CT enterography does not exclude important causes of small bowel bleeding. • Most lesions missed at CT-enterography are flat and can be detected by capsule endoscopy.

Leucobacter margaritiformis sp. nov., isolated from bamboo extract.

A Gram-positive aerobic rod-shaped non-motile bacterium designated A23(T) was isolated from bamboo extract that had been used to remove odor and was characterized to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain A23(T) belongs to the phylum Actinobacteria. The highest degree of sequence similarities was determined to be with Leucobacter salsicius M1-8(T) (96.7%), Leucobacter exalbidus K-540B(T) (96.4%), Leucobacter chromiireducens subsp. chromiireducens L-1(T) (96.4%), Leucobacter komagatae IFO 15245(T) (96.4%) and Leucobacter aerolatus Sj10(T) (96.4%). Chemotaxonomic data revealed that strain A23(T) possesses menaquinone MK11, and its cell wall peptidoglycan contained 2,4-diaminobutyric acid, alanine, glycine, glutamic acid and γ-aminobutyric acid. The polar lipid profile of strain A23(T) contained diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The predominant fatty acids were iso-C(16:0) (31.5%), anteiso-C(15:0) (43.2%) and anteiso-C(17:0) (13.9%), all of which corroborated the assignment of the strain to the genus Leucobacter. Based on these data, A23(T) (=KEMC 551-022(T) = JCM 17538(T)) should be classified as the type strain for a novel Leucobacter species, for which the name Leucobacter margaritiformis sp. nov. is proposed.

Long-term clinical outcomes and factors predictive of relapse after 5-aminosalicylate or sulfasalazine therapy in patients with mild-to-moderate ulcerative colitis.

BACKGROUND/AIMS: Clinical outcomes and factors predictive of favorable response after 5-aminosalicylates or sulfasalazine (5-ASA/sulfasalazine) treatment alone have not been well established in the treatment of mild to moderate ulcerative colitis (UC). We evaluated the clinical course of Korean UC patients treated with 5-ASA/sulfasalazine as a maintenance therapy in terms of relapse and predictive factors of clinical relapse. METHODOLOGY: A total 256 UC patients, treated with 5-ASA/sulfasalazine at the Severance Hospital between January 2000 and December 2008, were analyzed retrospectively. We sought to investigate relapse rates and to determine independent predictors for relapse. RESULTS: Of the 256 patients, 127 patients (49.6%) had a disease relapse. The cumulative relapse rate was 21.5% after 1 year, 36.5% after 2 years, 46.9% after 3 years and 59.8% after 5 years. On multivariate analysis, left-sided or extensive colitis at diagnosis (hazard ratio=1.46; 95% CI=1.01-2.10; p=0.04) and initial hemoglobin level <10.5g/dL (hazard ratio= 0.43; 95% CI=0.22-0.81; p=0.01) were found to be independent factors for clinical relapse. CONCLUSIONS: Our study showed that both disease extent at diagnosis and anemia were major predictive factors for clinical relapse after 5-ASA/sulfasalazine therapy for Korean patients with mild to moderate UC.

Stabilizing Adversarially Learned One-Class Novelty Detection Using Pseudo Anomalies.

Recently, anomaly scores have been formulated using reconstruction loss of the adversarially learned generators and/or classification loss of discriminators. Unavailability of anomaly examples in the training data makes optimization of such networks challenging. Attributed to the adversarial training, performance of such models fluctuates drastically with each training step, making it difficult to halt the training at an optimal point. In the current study, we propose a robust anomaly detection framework that overcomes such instability by transforming the fundamental role of the discriminator from identifying real vs. fake data to distinguishing good vs. bad quality reconstructions. For this purpose, we propose a method that utilizes the current state as well as an old state of the same generator to create good and bad quality reconstruction examples. The discriminator is trained on these examples to detect the subtle distortions that are often present in the reconstructions of anomalous data. In addition, we propose an efficient generic criterion to stop the training of our model, ensuring elevated performance. Extensive experiments performed on six datasets across multiple domains including image and video based anomaly detection, medical diagnosis, and network security, have demonstrated excellent performance of our approach.

Families Playing Animal Crossing Together: Coping With Video Games During the COVID-19 Pandemic.

The COVID-19 pandemic was stressful for everyone, particularly for families who had to supervise and support children, facilitate remote schooling, and manage work and home life. We consider how families coped with pandemic-related stress using the video game Animal Crossing: New Horizons. Combining a family coping framework with theorizing about media as a coping tool, this interview study of 27 families (33 parents and 37 children) found that parents and children individual coped with pandemic-related stress with media. Parents engaged in protective buffering of their children with media, taking on individual responsibility to cope with a collective problem. Families engaged in communal coping, whereby media helped the family cope with a collective problem, taking on shared ownership and responsibility. We provide evidence for video games as coping tools, but with the novel consideration of family coping with media.

Feasibility of salvage endoscopic mucosal resection by using a cap for remnant rectal carcinoids after primary EMR.

BACKGROUND: Secondary endoscopic treatment for remnant lesions of rectal carcinoid tumors after primary EMR or polypectomy is technically difficult because of fibrosis of residual tissues. EMR by using a cap (EMR-C), a method to resect the submucosal layer by suction by using a transparent cap, may be feasible as a salvage treatment. OBJECTIVE: To assess the feasibility of salvage EMR-C. DESIGN: Retrospective analysis. SETTING: Tertiary academic health care system. PATIENTS: Thirty-one patients who were referred for salvage treatment of a failed en bloc excision of rectal carcinoid tumors after primary EMR or polypectomy between January 2007 and December 2009. INTERVENTIONS: Salvage EMR-C for remnant carcinoid tumors in the rectum. MAIN OUTCOME MEASUREMENTS: Rate of complete resection, complications, length of procedure, and recurrence rate. RESULTS: The mean age of the patients was 52.0±11.8 years (range 30-78 years). The mean tumor size was 8.9±3.2 mm (range 5.0-13.0 mm). The mean procedure time was 9.1±3.7 minutes, and clear resection margins were pathologically confirmed in all 31 patients. The most common complication of salvage EMR-C was bleeding (7 patients, 22.6%), which was successfully treated by hemoclipping in all cases. The 1-year follow-up colonoscopy and CT results for all patients were negative for recurrence. LIMITATIONS: Retrospective design and limited cases at a single center. CONCLUSIONS: EMR-C is a feasible salvage therapeutic option for failed en bloc excision after primary endoscopic treatment of rectal carcinoid tumors.

Clinical outcomes and factors related to resectability and curability of EMR for early colorectal cancer.

BACKGROUND: EMR has emerged as an alternative therapeutic option for selected cases of early colorectal cancer (ECC). However, the factors associated with resectability and curability of EMR for ECC remain unknown. OBJECTIVE: To investigate clinical outcomes and factors related to resectability and curability in ECC cases treated with EMR. DESIGN: Retrospective study. SETTING: Tertiary-care academic medical center. PATIENTS: This study involved all patients in whom EMR was performed for ECC at Severance Hospital between March 1997 and August 2007. A total of 236 cases of ECC occurring in 231 patients (66.2% men) were enrolled. INTERVENTION: EMR. Curative surgical resection and lymph node dissection were used in cases that were incompletely cured by EMR. MAIN OUTCOME MEASUREMENTS: Resectability, curability, and recurrence. RESULTS: Complete cure was achieved for 162 lesions (68.6%). Of the remaining 74 cases (31.4%), 69 (29.2%) were incompletely cured, and the other 5 (2.1%) had an undetermined resection status and ultimately required supplementary surgical resection for curative treatment. Location on the right side of the colon, piecemeal resection, and submucosal carcinoma were independently associated with incomplete resection, whereas depressed tumor type was independently related to incomplete cure. Among the ECC cases completely cured by EMR and followed for more than a year (n = 118), local recurrence was observed in one case (0.8%) during the median follow-up period of 39.4 months (range 12.4-123.1 months). LIMITATIONS: Single-center, retrospective study. CONCLUSION: Our data show that EMR is feasible and could be an effective option for treatment of ECC if the technique is applied with the appropriate indications.