Mechanism of EBV inducing anti-tumour immunity and its therapeutic use.

Tumour-associated antigens (TAAs) comprise a large set of non-mutated cellular antigens recognized by T cells in human and murine cancers. Their potential as targets for immunotherapy has been explored for more than two decades1, yet the origins of TAA-specific T cells remain unclear. While tumour cells may be an important source of TAAs for T cell priming2, several recent studies suggest that infection with some viruses, including Epstein-Barr virus and influenza virus can elicit T cell responses against abnormally expressed cellular antigens that function as TAAs3,4. However, the cellular and molecular basis of such responses remains undefined. Here we show that expression of the Epstein-Barr virus signalling protein LMP1 in B cells provokes T cell responses to multiple TAAs. LMP1 signalling leads to overexpression of many cellular antigens previously shown to be TAAs, their presentation on major histocompatibility complex classes I (MHC-I) and II (MHC-II) (mainly through the endogenous pathway) and the upregulation of costimulatory ligands CD70 and OX40L, thereby inducing potent cytotoxic CD4+ and CD8+ T cell responses. These findings delineate a mechanism of infection-induced anti-tumour immunity. Furthermore, by ectopically expressing LMP1 in tumour B cells from patients with cancer and thereby enabling them to prime T cells, we develop a general approach for rapid production of autologous cytotoxic CD4+ T cells against a wide range of endogenous tumour antigens, such as TAAs and neoantigens, for treating B cell malignancies. This work stresses the need to revisit classical concepts concerning viral and tumour immunity, which will be critical to fully understand the impact of common infections on human health and to improve the rational design of immune approaches to treatment of cancers.

Does delayed EBV infection contribute to rising childhood cancers?

Childhood cancer is on the rise in high-income countries. Epidemiological studies suggest that reduced exposure to common infections in early life is to blame. However, no specific infection responsible for protection against cancer has been identified, and the underlying mechanisms remain a matter of speculation. Recent findings that Epstein-Barr virus (EBV) can induce antitumor immunity lead us to hypothesize that the delay in EBV infection in such countries might contribute to the increase in childhood cancers.

The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp.

This study aims to explore the potential inhibition effects of staurosporine isolated from a Streptomyces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimicrobial and antihypertensive activities. This research focuses on investigating the effects of staurosporine on suppressing the growth and development of nasal polyps and elucidating the underlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF-ß1 in the presence of staurosporine. The levels of α-smooth muscle actin (α-SMA), collagen type-I (Col-1), fibronectin, and phosphorylated (p)-Smad 2 were investigated using Western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-ß1 stimulated the production of Col-1, fibronectin, and α-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-ß1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine's role in nasal polyp management and provide insights into its mechanisms of action.

Can conservative treatment be effective for thoracolumbar injuries patients with TLICS scores of 4 or 5? An analysis of initial radiological findings and clinical risk factors for treatment failure.

BACKGROUND: This study aimed to assess the outcomes of conservative management in patients with thoracolumbar fractures classified with a Thoracolumbar Injury Classification and Severity (TLICS) score of 4 or 5, and to analyze initial imaging findings and clinical risk factors associated with treatment failure. METHODS: In this retrospective analysis, patients with thoracolumbar fractures and a TLICS score of 4 or 5, determined through MRI from January 2017 to December 2020, were included. Patients undergoing conservative treatment were categorized into two groups: Group 1 (treatment success) and Group 2 (treatment failure), based on initial and 6-month follow-up outcomes. Clinical data were compared between the two groups. Initial radiological assessments included three kyphosis measurements (Cobb angle, Gardner angle, and sagittal index [SI]), anterior and posterior wall height, and central canal compromise (CC). Additionally, risk factors contributing to treatment failure were analyzed. RESULTS: The conservative treatment group comprised 84 patients (mean age, 60.25 ± 15.53; range 22-85; 42 men), with 57 in Group 1 and 27 in Group 2. Group 2 exhibited a higher proportion of women, older age, and lower bone mass density (p = 0.001-0.005). Initial imaging findings in Group 2 revealed significantly greater values for Cobb angle, SI, and CC (p = 0.001-0.045 or < 0.001; with cutoff values of 18.2, 12.8, and 7.8%, respectively), and lower anterior wall height (p = 0.001), demonstrating good to excellent interobserver agreement (0.72-0.99, p < 0.001). Furthermore, osteoporosis was identified as a significant risk factor (odds ratio = 5.64, p = 0.008). CONCLUSION: Among patients with TLICS scores of 4 or 5, those experiencing conservative treatment failure exhibited unfavorable initial radiological findings, a higher proportion of women, advanced age, and osteoporosis. Additionally, osteoporosis emerged as a significant risk factor for treatment failure.

Family History of Gastric Cancer and Helicobacter pylori Treatment.

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

Novel MRI signs of ruptured disc in the cervical spine with intraoperative comparisons.

OBJECTIVES: To evaluate the diagnostic performance of two novel MRI signs for extruded disc (ED) and uncontained ED (ruptured disc, RD) in the cervical spine using intraoperative findings as reference. METHODS: This retrospective study included patients who underwent cervical spine MRI and surgery for disc pathology with intraoperative confirmation of RD from September 1, 2016, to January 31, 2021. Two radiologists determined whether the disc was extruded or ruptured with and without the aid of two novel MRI signs suggesting RD (sign 1: blurred margin of the disc; sign 2: mushroom-shaped disc). The diagnostic performance was analyzed using surgical findings as reference. Intra- and interobserver agreements were measured for each MRI sign. RESULTS: A total of 91 patients totaling 131 discs were enrolled (mean age: 56.02 ± 12.93; range: 26-88; 62 men and 29 women), of whom 62 were surgically confirmed with RD. When the diagnosis was based exclusively on existing ED definitions, ED was diagnosed with 62.9-79.0% sensitivity and 80.2% accuracy, whereas RD was diagnosed with 35.5-45.2% sensitivity and 67.9-71.0% accuracy. However, when the two novel MRI signs were used as an aid in the diagnosis, ED was diagnosed with 95.2-96.8% sensitivity and 84.0-88.5% accuracy, while RD was diagnosed with 95.2-96.8% sensitivity and 84.0-89.3% accuracy. Intra- and interobserver agreement was substantial (k = 00.77-0.86, 0.69-0.79, respectively, p < 0.001). CONCLUSIONS: The detection of two novel MRI signs on preoperative MRI can lead to a more accurate RD diagnosis. KEY POINTS: • The diagnostic sensitivity of MRI for cervical ruptured disc is very low (about 35-45 %) using the standardized definition of lumbar disc nomenclature. • Two novel MRI signs can lead to a more accurate diagnosis of the surgically confirmed ruptured disc in the cervical spine. • These two novel MRI signs showed substantial intra-and interobserver reliabilities.

Interaction between dietary potassium intake and TNF-α rs1800629 genetic polymorphism in gastric cancer risk: a case-control study conducted in Korea.

Mineral consumption has been suggested to have an impact on gastric cancer (GC) prevention. However, the protective effect of potassium against gastric carcinogenesis remains inconclusive. The causal link between inflammation and cancer is well established. Notably, potassium intake and potassium channels may play certain roles in regulating the production of TNF-α (TNF-α). We aimed to determine whether dietary potassium intake is related to the risk of GC. We further observed whether this association was modified by TNF-α rs1800629. We designed a case-control study comprising 377 GC cases and 756 controls. Information on dietary potassium intake was collected using a semiquantitative food frequency questionnaire. Genotyping was performed by the Affymetrix Axiom Exom 319 Array platform. Unconditional logistic regression models were used to assess associations. A significantly reduced GC risk was found for those who consumed higher dietary potassium levels (OR = 0·63, 95 % CI = 0·45, 0·89, P for trend = 0·009). In the dominant model, we observed a non-significant association between TNF-α rs1800629 and GC risk (OR = 1·01, 95 % CI = 0·68, 1·49). In females, those who were homozygous for the major allele (G) of rs1800629 with a higher intake of dietary potassium exhibited a decreased risk of GC (OR = 0·40, 95 % CI = 0·20, 0·78, P interaction = 0·041). This finding emphasises the beneficial effect of potassium intake on GC prevention. However, this association could be modified by TNF-α rs1800629 genotypes. A greater protective effect was exhibited for females with GG homozygotes and high potassium intake.

Risk of upper gastrointestinal cancer and death in persons with negative screening results: results from the National Cancer Screening Program in South Korea.

BACKGROUND: The Korea National Cancer Screening Program (KNCSP) offers upper endoscopy or upper gastrointestinal series (UGIS) biannually for people aged ≥ 40 years. This study aimed to assess the effect of negative screening results on the incidence of and mortality from upper gastrointestinal (GI) cancer. METHODS: A population-based retrospective cohort of 15,850,288 men and women was constructed using data from 3 national databases. The participants were followed until the end of 2017 for data on cancer incidence and in 2019 for data on the vital status. Cox proportional hazard model with time-varying exposure was used to assess the association. RESULTS: By the end of the follow-up period, 230,783 upper GI cancer cases and 99,348 upper GI cancer deaths were recorded. Negative gastric cancer screening was significantly associated with a lower risk of upper GI cancer in both UGIS (adjusted hazard ratio [aHR] = 0.81, 95% CI = 0.80-0.82) and upper endoscopy (aHR = 0.67, 95% CI = 0.67-0.68) groups. The HRs for upper GI mortality were 0.55 (95% CI = 0.54-0.56) and 0.21 (95% CI = 0.21-0.22) for the UGIS and upper endoscopy groups, respectively. The most significant reductions in the risk of upper GI cancer (UGIS: aHR = 0.76, 95% CI = 0.74-0.77; upper endoscopy: aHR = 0.60, 95% CI = 0.59-0.61) and death (UGIS: aHR = 0.54, 95% CI = 0.52-0.55; upper endoscopy: aHR = 0.19, 95% CI = 0.19-0.20) were observed among individual aged 60-69 years. CONCLUSION: Negative screening cases, especially in upper endoscopy of the KNCSP, were associated with an overall reduction in the risk of and mortality from upper GI cancer.

Inhibition of voltage-dependent K+ currents of rabbit coronary arterial smooth muscle cells by the atypical antipsychotic paliperidone.

Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage-dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells. Paliperidone reduced Kv channel activity in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50 ) of 16.58 ± 3.03 µM and a Hill coefficient of 0.60 ± 0.04. It did not significantly shift the steady-state activation or inactivation curves, suggesting that the drug did not affect the gating properties of Kv channels. In the presence of paliperidone, the application of 20 repetitive depolarizing pulses at 1 and 2 Hz gradually increased the inhibition of the Kv current. Further, the recovery time constant after Kv channel inactivation was increased by paliperidone, indicating that it inhibited the Kv channel in a use (state)-dependent manner. Its inhibitory effects were reduced by pretreatment with a Kv1.5 subtype inhibitor. However, pretreatment with a Kv2.1 or Kv7 inhibitor did not reduce its inhibitory effect. We conclude that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration- and use (state)-dependent manner without changing channel gating.

Effectiveness of intraoperative table modification for achieving lumbar lordosis in multilevel lumbar fusion surgery: a propensity score-matched study.

BACKGROUND: In multilevel posterior lumbar interbody fusion (PLIF) with posterior screw fixation, obtaining sufficient lumbar lordosis (LL) is difficult, especially in patients with osteoporosis. We performed intraoperative table modification (TM) using gravitational dropping of the patient's lumbar spine, to improve restoration of LL. METHODS: We retrospectively reviewed the medical records of patients who underwent three- or four-level PLIF between 2005 and 2019. One hundred eleven patients were enrolled, with 96 patients receiving non-TM-PLIF and 15 patients receiving TM-PLIF. Radiological parameters, including segmental lordosis (SL), LL, sacral slope (SS), pelvic incidence, and pelvic tilt, were measured. Clinical outcomes were measured using a visual analogue scale (VAS) for the back and leg preoperatively and at the last follow-up. Additionally, the correlation between the bone mineral density (BMD) and the radiological parameters was calculated for TM-PLIF. We performed propensity score matching between the groups to control the baseline difference. RESULTS: We found a statistically better correction between immediate and last follow-up postoperative SL (p = 0.04), as well as between preoperative and last follow-up SL (p < 0.01) in the TM-PLIF group compared to that in the non-TM-PLIF group. VAS for the back and leg were not significantly different between the two groups. Additionally, the efficacy of lordosis correction in the TM-PLIF group showed a statistically significant negative correlation between BMD and the SS change both before and after the surgery (rho = -0.60, p = 0.02). CONCLUSION: Whilst further study is required to conclusively establish its efficacy, TM-PLIF (table modification using gravitational dropping) shows potential advantages for restoring and maintaining LL in multilevel lumbar fusion, particularly in cases with low BMD.

Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Sargassum horneri Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay.

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-ß1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-ß1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-ß1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-ß1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS: On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS: The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS: There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.

Riboflavin intake, MTRR genetic polymorphism (rs1532268) and gastric cancer risk in a Korean population: a case-control study.

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The OR and 95 % CI were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR = 0·52, 95 % CI 0·28, 0·97, Ptrend = 0·031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT + TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93 % higher GC risk (OR = 1·93, 95 % CI 1·09, 3·42, Pinteraction = 0·037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC + TT carriers, particularly the T+ carriers, with marginal significance (OR = 0·54, 95 % CI 0·28, 1·02, Pinteraction = 0·037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated-type early gastric cancer meeting the expanded criteria: a systematic review and meta-analysis.

BACKGROUND: There have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC. METHODS: We searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model. RESULTS: Overall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26-3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60-2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42-4.35) and higher recurrence (RR 12.61; 95% CI 3.43-46.37), gastric recurrence (RR 11.25; 95% CI 3.06-41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47-37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts. CONCLUSION: Although OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Efficacy of endoscopic management for anastomotic leakage after gastrectomy in patients with gastric cancer.

BACKGROUND: Anastomotic leakage (AL) after gastrectomy in gastric cancer patients is associated with high mortality rates. Various endoscopic procedures are available to manage this postoperative complication. The aim of study was to evaluate the outcome of two endoscopic modalities, clippings and stents, for the treatment of AL. PATIENTS AND METHODS: There were 4916 gastric cancer patients who underwent gastrectomy between December 2007 and January 2016 at the National Cancer Center, Korea. A total of 115 patients (2.3%) developed AL. Of these, 85 patients (1.7%) received endoscopic therapy for AL and were included in this retrospective study. The endpoints were the complete leakage closure rates and risk factors associated with failure of endoscopic therapy. RESULTS: Of the 85 patients, 62 received endoscopic clippings (with or without detachable snares), and 23 received a stent insertion. Overall, the complete leakage closure rate was 80%, and no significant difference was found between the clipping and stent groups (79.0% vs. 82.6%, respectively; P = 0.89). The complete leakage closure rate was significantly lower in the duodenal and jejunal stump sites (60%) than esophageal sites (86.1%) and gastric sites (94.1%; P = 0.026). The multivariate analysis showed that stump leakage sites (adjusted odds ratio [aOR], 4.51; P = 0.031) and the presence of intra-abdominal abscess (aOR, 4.92; P = -0.025) were associated with unsuccessful leakage closures. CONCLUSIONS: Endoscopic therapy using clippings or stents is an effective method for the postoperative management of AL in gastric cancer patients. This therapy can be considered a primary treatment option due to its demonstrated efficacy, safety, and minimally invasive nature.

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Dieckol induces cell cycle arrest by down-regulating CDK2/cyclin E in response to p21/p53 activation in human tracheal fibroblasts.

The phlorotannin derivative dieckol isolated from Ecklonia cava has been shown to exhibit anti-inflammatory, anti-bacterial, anti-oxidative anti-adipogenic and anti-stenosis activity. However, the role of dieckol in cyclin-dependent kinase 2 (CDK2)/cyclin E signalling, which regulates fibrosis development, has not yet been determined. In this study, we report that dieckol-suppressed cell proliferation through the cell cycle arrest of Hs680.Tr human tracheal fibroblasts. Following consecutive purification, dieckol was identified as a potent bioactive compound. The results showed that dieckol had significant anti-proliferative activity against Hs680.Tr human tracheal fibroblastsWestern blotting analysis also found that dieckol dose-dependently induced the cell cycle arrest of Hs680.Tr fibroblasts in the G0/G1 phase, accompanied by the downregulation of CDK2 and cyclin E and the upregulation of p21 and p53. As attested by molecular docking study, the dieckol interacted with the core interface residues in transforming growth factor-ß receptor with high affinity. These findings suggest that dieckol from E. cava inhibits the cell proliferation of Hs680.Tr, potentially through p21- and p53-mediated G0/G1 cell cycle arrest.

Effects of Smart Advanced Life Support protocol implementation including CPR coaching during out-of-hospital cardiac arrest.

PURPOSE: The aim of this study was to compare out-of-hospital cardiac arrest (OHCA) outcomes before and after implementation of Smart Advanced Life Support (SALS) protocol incorporating changes in cardiopulmonary resuscitation (CPR) assistance and coaching by physicians via real-time video calls. METHODS: A prospective before-and-after multi-regional observational study was conducted between January 2014 and December 2018. In January 2016, emergency medical service (EMS) providers adopted an integrated CPR coaching by physicians via real-time video call via SALS to treat patients with OHCA focusing on high-quality cardiopulmonary resuscitation. Propensity score matching was performed to match patients. Patients' outcomes using conventional protocol were then compared with those of patients using the SALS protocol. RESULTS: Among 26,349 OHCA cases, 2351 patients and 7261 patients were enrolled during the pre-intervention and the post-intervention periods, respectively. Multivariate analysis showed that SALS was independently associated with favorable neurological outcomes [odds ratio (OR): 2.20; 95% confidence interval (CI): 1.62-2.99]. A total of 2096 patients were propensity score-matched and the two groups were well balanced. In the matched cohort, the use of SALS protocol was still associated with increased prehospital return of spontaneous circulation (ROSC) (OR: 3.83, 95% CI: 2.80-5.26), survival to discharge (OR: 1.68; 95% CI: 1.20-2.34), and favorable neurological outcomes (OR: 1.83; 95% CI: 1.19-2.82). CONCLUSION: A multidisciplinary SALS protocol for the resuscitation of patients with OHCA was associated with increased prehospital ROSC, survival to discharge, and good neurologic outcomes compared with traditional resuscitation protocol.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.