Efficacy and safety of oral sodium sulfate tablet compared with 1-L polyethylene glycol plus ascorbate: a prospective, randomized, endoscopist-blinded trial.

BACKGROUND AND AIM: Low-volume bowel preparation solutions, including 1-L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1-L PEG-A. METHODS: A single-center, prospective, controlled study was performed with randomization into the OST (group A) and 1-L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination. RESULTS: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1-sided 97.5% lower confidence limit -7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years. CONCLUSIONS: Both OST and 1-L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability.

Clinical outcomes of colonoscopic polypectomy with strategic surveillance colonoscopies in patients with 10 or more polyps.

The clinical usefulness of repeat colonoscopic polypectomy in patients with numerous polyps has not been sufficiently determined. We aimed to analyze the clinical outcomes of colonoscopic polypectomy with surveillance colonoscopies in patients with ≥ 10 polyps. We reviewed the medical records of 152 patients who underwent polypectomy of ≥ 10 polyps at the baseline colonoscopy. We investigated polyp number, polyp size, polypectomy method, procedure time, and adverse events of the baseline colonoscopy. We also investigated the frequency and interval of surveillance colonoscopies and their findings. The mean number of polyps detected at the baseline colonoscopy was 20.0, of which 16.0 polyps were endoscopically resected. The mean size of the largest polyp was 13.4 mm. The mean procedure time was 54.9 min. Post-polypectomy bleeding occurred in 6 (3.9%) patients, all of whom were treated conservatively. No patients developed perforation. With an increasing number of surveillance colonoscopies, the number of detected polyps and the procedure time decreased. Surveillance colonoscopies identified colorectal cancer only in three patients (2.0%), all of which were mucosal cancers that could be curatively treated by polypectomy. Colonoscopic polypectomy with repeat surveillance colonoscopies is a clinically effective, efficient, and safe management option in patients with ≥ 10 polyps.

Impact of Sarcopenia on Clinical Course of Inflammatory Bowel Disease in Korea.

BACKGROUND AND AIMS: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD. METHODS: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm2/m2 for male and < 31 cm2/m2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia. RESULTS: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782-2.391; P = 0.272). CONCLUSION: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD.

Improved adenoma detection by a novel distal attachment device-assisted colonoscopy: a prospective randomized controlled trial.

BACKGROUND AND AIMS: WingCap (A&A Medical Supply LLC, Seongnam, South Korea) is a novel distal attachment device for colonoscopy that combines a cap and an existing mucosal exposure device, such as Endocuff Vision (Arc Medical Design Ltd, Leeds, UK) and AmplifEYE (Medivators Inc, Minneapolis, Minn, USA). We aimed to investigate whether WingCap-assisted colonoscopy can improve the adenoma detection rate (ADR) and adenoma per colonoscopy (APC) and simultaneously shorten cecal intubation time compared with standard colonoscopy. METHODS: We conducted a single-center, prospective, randomized controlled trial for outpatients aged ≥18 years undergoing colonoscopy. The primary outcome was ADR differences with the assistance of WingCap. Secondary outcomes were APC and other colonoscopy quality indicators, such as cecal intubation and withdrawal times. RESULTS: In total, 537 patients were randomized for WingCap-assisted or standard colonoscopy. Their mean age was 59.3 years, and 48.5% were men. ADR was significantly higher in the WingCap group than in the control group (37.2% vs 26.6%, P = .012). APC was greater with WingCap than with standard colonoscopy (.72 ± 1.34 vs .45 ± 0.97, P = .008), prominently for nonpedunculated (.65 ± 1.25 vs .42 ± .95, P = .015) and diminutive (.42 ± .94 vs .20 ± .64, P = .002) adenomas. With WingCap, ADR and APC significantly increased for beginner endoscopists, whereas a modest increase was seen for experienced endoscopists. There were no differences in cecal intubation and withdrawal times between the 2 arms. No serious adverse event was associated with the use of WingCap. CONCLUSIONS: WingCap-assisted colonoscopy was tolerable and efficacious for improving ADR and APC compared with standard colonoscopy, especially for nonpedunculated and diminutive adenomas and for beginner endoscopists. (Clinical trial registration number: KCT0005214.).

Idiopathic Nonsurgical Pneumoperitoneum in Healthy Individuals after Endoscopy: Coincidence or Consequence?

Idiopathic pneumoperitoneum has an unknown etiology despite exploratory laparotomy. However, it may occur without definite abdominal symptoms; thus, adequate management could be in clinical dilemma. We experienced three cases of idiopathic nonsurgical pneumoperitoneum in healthy individuals during a health check-up. Their cases were not accompanied by any relevant etiology or definite abdominal symptoms. All of the three cases exhibited a benign clinical course. The three patients underwent an abdominal computed tomography (CT) scan as part of a health check-up program, which incidentally revealed free air in the right paracolic gutter without evidence of visceral perforation or inflammation. Among the three cases, two patients underwent colonoscopy before abdominal CT, whereas one patient did not. Two cases were completely asymptomatic and were observed without any treatment in the outpatient clinic. Only the third case with minimal symptoms was treated conservatively for a short time. If a small amount of free air typically located in the right paracolic gutter is detected in the absence of perforation during colonoscopy, close observation without unnecessary treatment would be sufficient.

The Influence of Face Shields on the Quality of Colonoscopy in the Era of the COVID-19 Pandemic.

Background/Aims: The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy. Methods: We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020. Results: Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists. Conclusions: Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.

High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD). METHODS: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871). RESULTS: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities. CONCLUSIONS: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure.

A Surveillance Endoscopy Strategy Based on Local Recurrence Rates after Colorectal Endoscopic Submucosal Dissection.

BACKGROUNDS: It is not clear when and how frequently surveillance endoscopy should be performed after colorectal endoscopic submucosal dissection (ESD). We aimed to suggest a surveillance endoscopy strategy by investigating the cumulative local recurrence rates and identifying risk factors for local recurrence after colorectal ESD. METHODS: We reviewed the medical records of 770 patients who underwent colorectal ESD for 778 lesions at our institution from 2005 to 2016. We investigated the cumulative local recurrence rates and risk factors for local recurrence. RESULTS: Local recurrence developed in 12 (1.5%) of 778 lesions during the follow-up period of 37.4 ± 31.7 months. The one-, three-, and five-year cumulative local recurrence rates were 0.4%, 1.7%, and 2.2%, respectively. The risk factors for local recurrence were piecemeal resection (odds ratio (OR) 3.948, 95% confidence interval (CI) 1.164-13.385; p = 0.028) and histological incomplete resection (OR 8.713, 95% CI 2.588-29.334; p < 0.001). Local recurrence tended to develop frequently after ESD of early cancers. CONCLUSIONS: Short-term surveillance endoscopy should be recommended after piecemeal ESD, histological incomplete resection, and ESD of early colorectal cancers. Surveillance endoscopy with longer intervals can be suggested after en bloc ESD with the histological complete resection of benign colorectal tumors.

Risk and characteristics of tuberculosis after anti-tumor necrosis factor therapy for inflammatory bowel disease: a hospital-based cohort study from Korea.

BACKGROUND: Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment. METHODS: The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group. RESULTS: Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862). CONCLUSIONS: In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy.

The Clinical Features of Inflammatory Bowel Disease in Patients with Obesity.

Methods: We retrospectively reviewed the medical records of IBD patients who visited Asan Medical center. We used a large, well-characterized referral center-based cohort. The clinical features of IBD patients with body mass index (BMI) over 30 and matched controls with BMI under 30 were compared. Results: Among the 6,803 IBD patients enrolled in the Asan IBD Registry between June 1989 and December 2016, we identified 16 patients with Crohn's disease (CD) and 27 patients with ulcerative colitis (UC) whose BMI was over 30 at the time of diagnosis. Their clinical characteristics and course were compared with those of 64 and 108 matched patients with CD and UC, respectively. There were no significant differences in the risk of using steroids (hazards ratio (HR) = 0.633 and P=0.254), immunomodulators (HR = 0.831 and P=0.517), and anti-tumor necrosis factor (TNF) therapy (HR = 1.539 and P=0.351) and risk of bowel resections (HR = 1.858 and P=0.231) between CD patients with BMI over 30 and those with BMI under 30; similarly, UC patients did not show significant differences in the risk of using steroids (HR = 0.613 and P=0.145), immunomodulators (HR = 0.492 and P=0.111), anti-TNF therapy (HR = 0.385 and P=0.095), and risk of colectomy (HR = 0.262 and P=0.104). In the subgroup analysis, under-weight UC patients had a higher cumulative probability of needing steroids (HR = 0.2510 and P=0.042), needing immunomodulators (HR = 0.097 and P=0.014), and a higher risk of receiving colectomy (HR = 0.024 and P=0.019) than obese UC patients. Conclusions: Obese IBD patients with CD or UC did not show significantly different clinical features from nonobese IBD patients.

[Colonic Mass Secondary to Sevelamer-associated Rectal Ulcer].

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic "fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

Frequency of Positive Conversion of Interferon-Gamma Release Assay Results Among Patients With Inflammatory Bowel Disease Treated With Non-tumor Necrosis Factor Inhibitors.

Considering the risk of reactivation of latent tuberculosis infection (LTBI), not only before starting tumor necrosis factor inhibitors but also before non-TNF inhibitor therapy, LTBI screening is routinely recommended for patients with inflammatory bowel disease (IBD). However, data on the positive conversion of LTBI test results during non-TNF inhibitor therapy are scarce. Among IBD patients treated with vedolizumab and/or ustekinumab, a total of 91 patients who had negative baseline interferon-gamma release assay (IGRA) results, assessed by QuantiFERON®-TB Gold In-tube or QuantiFERON®-TB Gold Plus, were enrolled. Serial LTBI test results after starting non-TNF inhibitor therapy were collected, and patients' clinical characteristics were analyzed. Positive IGRA conversion was observed in six of 91 patients (6.6%). The cumulative IGRA conversion-free survival rates after starting therapy were 97.7% after 1 year and 86.7% after 2 years. Ulcerative colitis was more common among converters compared with non-converters (66.7 vs. 23.5%, P = 0.040). Among six converters, four had been treated with vedolizumab, one with ustekinumab, and the other with vedolizumab followed by ustekinumab. All six patients had been previously exposed to TNF inhibitors before non-TNF inhibitor therapy: five to infliximab and one to both infliximab and adalimumab. After positive IGRA conversion, none of the six converters developed active tuberculosis while maintaining non-TNF inhibitor therapy (median 6.8 months, range 0.4-32.1 months). Positive IGRA conversion among IBD patients treated with vedolizumab and/or ustekinumab appears to occur somewhat frequently, but its clinical implications remain to be elucidated.

Rates and Risk Factors for Interval Gastric Cancers at Screening Gastroscopy.

BACKGROUNDS/AIMS: Interval gastric cancers (GCs) can be encountered during screening gastroscopy. This study investigated the rate of interval GCs and their risk factors. MATERIALS AND METHODS: We retrospectively investigated subjects who underwent screening gastroscopy from 2005 to 2017 in a university hospital and were diagnosed with GC. Subjects were grouped based on their endoscopic images and descriptive results into interval GC and initially diagnosed GC groups. Interval GCs were defined when endoscopic results within the previous 3 years were negative for GC. The clinico-pathological characteristics of the groups and risk factors for interval GCs were evaluated. RESULTS: Of 54 724 subjects who underwent screening gastroscopy, 234 were diagnosed with GC, of which 43 were interval GCs. The rate of interval GCs was 18.4% (43/234, mean age 61.6 years). Interval GCs were smaller than initially diagnosed GCs (1.6 vs 1.9 cm, P = .011). They were located in the low-to-mid-body in 44.2%, antrum in 48.8%, and high body and cardia in 7%. Their observation time was shorter (248.74 vs 410.64 sec, P = .032). In multivariate analysis, they were associated with short observation time (odds ratio [OR] 0.99, 95% CI 0.994-0.998, P < .001) and location in the low-to-mid-body (OR 2.12, 95% CI 1.071-4.181, P = .031), although differentiation, ulcerated type, metaplasia, Helicobacter pylori infection, and endoscopists' experience were not associated with interval GCs. CONCLUSIONS: The rate of interval GCs was significant during screening gastroscopy. They might be reduced by increasing observation time, focusing on smaller lesions, and observing the low-to-mid-body of the stomach more carefully.

Cell-permeable transgelin-2 as a potent therapeutic for dendritic cell-based cancer immunotherapy.

BACKGROUND: Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy. METHODS: To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout (Tagln2-/-) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T-DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA+ B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy. RESULTS: We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2-/- BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA+ B16F10 melanoma cells in mice. Tagln2-/- BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4+ T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis. CONCLUSION: This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.

Correlation between Three-Dimensional Volume and Malignant Potential of Gastrointestinal Stromal Tumors (GISTs).

BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs) are rare diseases of the gastrointestinal tract but they are the most common gastrointestinal tumors of mesenchymal origin. Since most GISTs have malignant potential, their probability of malignant progression must be evaluated. This study was conducted to examine the correlation between three-dimensional GIST volume measured by CT and malignant potential. MATERIALS AND METHODS: A retrospective study was performed on 70 patients diagnosed with GIST after surgical resection in Hanyang University Seoul Hospital from 2012 to 2017. Linear regression analysis was used to establish which between the length of the long axis of GISTs, originally considered a predictor of malignancy, and their volume was a more accurate predictor of malignancy. Tumor dimensions were measured by CT. RESULTS: Data were analyzed using the chi-square test or Student's t-test and logistic regression. Of the GISTs, 53 (75.71%) were in the stomach, 3 (4.29%) in the small intestine, and 14 (20.0%) in the large intestine. The mean age of the malignant GIST group was significantly higher than that of the benign GIST group (p = 0.032), their tumor long axes were significantly greater (p = 0.073), their tumor volumes were significantly larger (p = 0.001), and the frequency of tumor necrosis was higher (p = 0.001). In multivariate analysis, malignant GIST was associated with location in organs other than the stomach (OR 7.846, 95% CI 1.293-47.624, p = 0.025), longer axis (OR 1.037, 95% CI 1.011-1.065, p = 0.006), larger volume (OR 1.003, 95% CI 1.000-1.006, p = 0.029), and necrosis (OR 12.222, 95% CI 1.945-76.794, p = 0.008). The mean age of the recurrent GIST group was higher than that of the non-recurrent group (p = 0.045), their tumor long axes were significantly longer (p = 0.005), and their volumes were greater, but this last difference was not significant (p = 0.072). CONCLUSIONS: Tumor volume can be considered an additional risk factor in assessing the malignant potential of GISTs and tends to increase in recurrent GISTs.

The Uncertain Effect of Antimicrobial Therapy in the Treatment of Patients with Ischemic Colitis.

Although antimicrobial therapy is recommended for patients with moderate or severe ischemic colitis, its beneficial effects are unclear. In the present study, the role of antimicrobial therapy in the treatment of ischemic colitis was investigated. Patients with ischemic colitis were retrospectively identified between January 2004 and June 2019. The characteristics and outcomes of patients who received antibiotics (antibiotics group) and those who did not (no-antibiotics group) were compared. Clinical outcomes included death, surgery, and readmission within 30 days, fasting duration, and hospital stay. Data from 186 patients were analyzed; 122 patients were in the antibiotics group and 64 in the no-antibiotics group. Composite outcome of death, surgery, and readmission within 30 days occurred in 3.3% of patients in the antibiotics group and 3.1% of patients in the no-antibiotics group (p > 0.999). Fasting duration was not significantly different between the two groups (median days, 4.0 vs. 4.0, p = 0.253). However, hospital stays were longer in the antibiotics group than in the no-antibiotics group (median days, 9.0 vs. 7.0, p = 0.043). In patients with ischemic colitis, there was no statistically significant difference in the incidence of death, surgery, and readmission within 30 days between patients who received antibiotics and those who did not receive antibiotics.

Potentiating the Antitumor Activity of Cytotoxic T Cells via the Transmembrane Domain of IGSF4 That Increases TCR Avidity.

A robust T-cell response is an important component of sustained antitumor immunity. In this respect, the avidity of TCR in the antigen-targeting of tumors is crucial for the quality of the T-cell response. This study reports that the transmembrane (TM) domain of immunoglobulin superfamily member 4 (IGSF4) binds to the TM of the CD3 ζ-chain through an interaction between His177 and Asp36, which results in IGSF4-CD3 ζ dimers. IGSF4 also forms homo-dimers through the GxxVA motif in the TM domain, thereby constituting large TCR clusters. Overexpression of IGSF4 lacking the extracellular (IG4ΔEXT) domain potentiates the OTI CD8+ T cells to release IFN-γ and TNF-α and to kill OVA+-B16F10 melanoma cells. In animal models, IG4ΔEXT significantly reduces B16F10 tumor metastasis as well as tumor growth. Collectively, the results indicate that the TM domain of IGSF4 can regulate TCR avidity, and they further demonstrate that TCR avidity regulation is critical for improving the antitumor activity of cytotoxic T cells.

Low Alanine Aminotransferase Cut-Off for Predicting Liver Outcomes; A Nationwide Population-Based Longitudinal Cohort Study.

BACKGROUND AND AIM: Recent practice guidelines suggest healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the "low cut off" for liver related outcomes in the general population. METHODS: A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared. RESULTS: Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose, and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was a significant independent predictor for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (p-values < 0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88). CONCLUSIONS: New low ALT cut-off showed good prediction power for liver related unfavorable outcomes.