This study was aimed at investigating the clinical efficacy of probiotics in pneumonia patients. To this end, we enrolled 80 participants diagnosed with pneumonia at Naval Pohang Hospital, Pohang, ...Korea, from May 2016 to January 2017. The participants were randomly assigned to the control and probiotic groups depending on whether they received probiotics. All participants clinically improved but 22.6% of the participants complained of abnormal stool habits after pneumonia treatment. In comparison, fever duration was significantly shorter in the probiotic group, and the group exhibited an improved general condition. The probiotic group also showed better stool characteristics according to the Bristol stool scale (P = 0.009). Notably, the serum hs-CRP levels were significantly lower in the probiotic group at 2 weeks of treatment (P = 0.015), and all participants in the probiotic group achieved their levels within the normal range. Flow cytometry was used to analyze T-helper 17 (Th17) cells and regulatory T cells (Tregs). Tregs were promoted and the Th17 cell/Treg ratio was suppressed after 2 weeks of treatment in the probiotic group (P = 0.007 and 0.037, respectively). This study demonstrated that probiotics improved clinical symptoms and normalized inflammatory biomarker levels in patients with pneumonia. Early infection and inflammation recovery may be due to the immunomodulatory effects of probiotics by facilitating the subset of Tregs and suppressing the Th17 cell/Treg ratio.
Antegrade dissection reentry with Stingray device (Boston Scientific, Marlborough, MA) accounts for 20–34% of the chronic total occlusion (CTO) cases in the various hybrid operators' CTO registries ...and is an important component of CTO crossing algorithms. The Stingray device can facilitate antegrade dissection and reentry, however its use is low outside North America and Europe. The Asia Pacific CTO Club along with three experience Stingray operators from the US, Europe and India, created an algorithm guiding use of the CrossBoss and Stingray catheter. This APCTO Stingray algorithm defines when to use the CrossBoss and Stingray device recommending a reduction in CrossBoss use except for in‐stent restenosis lesions and immediate transition from knuckle wiring to the Stingray device. When antegrade wiring fails, choice of Stingray‐facilitated reentry versus parallel wiring depends on operator experience, device availability, cost concerns, and anatomical factors. When the antegrade wire enters the subintimal space, we recommend using a rotational microcatheter to produce a channel and deliver the Stingray balloon—so called the “bougie technique.” We recommend early switch to Stingray rather than persisting with single wire redirection or parallel wire. We recommend choosing a suitable reentry zone based on preprocedural computer tomography or angiogram, routine use of stick and swap, routine use of Subintimal TRAnscatheter Withdrawal (STRAW) through the Stingray balloon, and the multi stick and swap technique. We believe these techniques and algorithm can facilitate incorporation of the Stingray balloon into the practice of CTO interventionists globally.
Although the hybrid chronic total occlusion (CTO) algorithm had many excellent recommendations, there has been infrequent adoption in the Asia Pacific region. The Asia Pacific CTO club propose an ...algorithm for case selection based on the Japan-CTO score and a new CTO algorithm, which is applicable globally. This algorithm allows for differing skill sets and equipment availability and contains practical teaching for CTO percutaneous coronary intervention. Similar to the hybrid algorithm there are 3 main questions that determine whether the primary approach is antegrade or retrograde: 1) is there proximal cap ambiguity; 2) is the distal vessel of poor quality; and 3) are there interventional collaterals present. In contrast to the hybrid algorithm occlusion length alone does not determine the choice of either a wire escalation strategy or a dissection re-entry strategy. Rather a combination of factors including ambiguity of the vessel course, severe calcification, tortuosity, length, and previous failure are used to determine this. The role of intravascular ultrasound–guided entry to overcome proximal cap ambiguity and the CrossBoss catheter in occlusive in-stent restenosis are highlighted in the algorithm. Both the parallel wire technique and dissection re-entry with the Stingray system have been included as options when the initial antegrade wire passage fails. Intravascular ultrasound–guided wiring along with limited subintimal tracking and re-entry are included as final options in the algorithm. Finally, the algorithm incorporates guidance on when to stop the procedure. It is hoped that this algorithm will serve as the basis for future CTO percutaneous coronary intervention proctoring and training.
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MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial-mesenchymal transition (EMT) in ...colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3'-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of
-AKT and
-ERK by targetting TM4SF1 in PGE2-induced cells.Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.
Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of ...LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of the present study was to investigate whether LCN2 is associated with proliferation and the epithelial–mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. LCN2 was preferentially expressed in CRC cells compared to normal tissues. However, LCN2 expression was significantly lower in metastatic or advanced‐stage CRC than in non‐metastatic or early stage CRC. Knockdown of LCN2 using small interfering RNA (siRNA) in CRC cells expressing a high level of LCN2 induced cell proliferation and a morphological switch from an epithelial to mesenchymal state. Furthermore, downregulation of LCN2 in CRC cells increased cell migration and invasion involved in the regulation of EMT markers. Knockdown of LCN2 also induced glucose consumption and lactate production, accompanied by an increase in energy metabolism‐related genes. Taken together, our findings indicated that LCN2 negatively modulated proliferation, EMT and energy metabolism in CRC cells. Accordingly, LCN2 may be a candidate metastasis suppressor and potential therapeutic target in CRC.
Our study provides new insight into the role of Lipocalin 2 and the underlying molecular mechanisms in colorectal cancer progression, suggesting Lipocalin 2 as a potential diagnostic marker and therapeutic target in colorectal cancer.
: The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta
(rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in ...treating erosive gastritis.
This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or Mucosta
thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta
, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta
, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated.
According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta
-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta
-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was -4.01% (95% confidence interval CI, -13.09% to 5.06%) in the ITT analysis and -4.44% (95% CI, -13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta
-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates.
The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta
) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.
This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared ...with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P < 0.001). Similarly, 30-day mortality was also significantly higher in patients with HCC (53.3% vs. 23.2%, P < 0.001). In the multivariate analysis, HCC, renal impairment, CTP grade C, and antibiotic resistance were independent factors for initial treatment failure. Furthermore, HCC, hepatic encephalopathy, MELD score, and initial treatment failure were independent risk factors for 30-day mortality, with statistically significant poor survival outcomes in patients with HCC (P < 0.001). In conclusion, HCC is an independent risk factor for initial treatment failure and high short-term mortality in patients with cirrhosis with SBP. It has been suggested that more attentive therapeutic strategies are required to improve the prognosis of patients with HCC and SBP.
Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node ...metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.
H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and ...safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis.
A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared.
According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different.
DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).
Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of ...fexuprazan in patients with acute or chronic gastritis.
In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.
Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions.
Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).
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