MEF2C regulates NK cell effector functions through control of lipid metabolism.

Natural killer (NK) cells are a critical first line of defense against viral infection. Rare mutations in a small subset of transcription factors can result in decreased NK cell numbers and function in humans, with an associated increased susceptibility to viral infection. However, our understanding of the specific transcription factors governing mature human NK cell function is limited. Here we use a non-viral CRISPR-Cas9 knockout screen targeting genes encoding 31 transcription factors differentially expressed during human NK cell development. We identify myocyte enhancer factor 2C (MEF2C) as a master regulator of human NK cell functionality ex vivo. MEF2C-haploinsufficient patients and mice displayed defects in NK cell development and effector function, with an increased susceptibility to viral infection. Mechanistically, MEF2C was required for an interleukin (IL)-2- and IL-15-mediated increase in lipid content through regulation of sterol regulatory element-binding protein (SREBP) pathways. Supplementation with oleic acid restored MEF2C-deficient and MEF2C-haploinsufficient patient NK cell cytotoxic function. Therefore, MEF2C is a critical orchestrator of NK cell antiviral immunity by regulating SREBP-mediated lipid metabolism.

Design, synthesis, biological evaluation study of spirocyclic POM analogues as novel MmpL3 anti-tubercular agent.

We present the development of a phenyl oxazole methyl (POM) core structure with spirocyclic derivatives as part of our efforts to discover innovative anti-tuberculosis agents. Derivatives of spirocyclic POM were synthesized and evaluated for their inhibitory effects on M.tuberculosis (M. tb) H37Rv. Notably, compound 5c displayed potent anti-tubercular activity with MIC value of 0.206 µM in culture broth medium. Furthermore MIC values of compound 5c against DS/MDR/pre-XDR clinical isolates ranged from 0.34 to 0.68 µg/mL, 0.17 to 0.68 µg/mL, and 0.17 to 0.34 µg/mL, respectively. Also, compound 5c with favorable ADME and PK properties was not cytotoxic to THP-1 human cells. Based on the spontaneous mutant generation, we have identified the target of compound 5c to be MmpL3. The computational docking study suggested its plausible binding mode against MmpL3. There is no approved drug targeting this target yet, and the outcomes of the presented research will contribute to the future discovery of novel anti-tuberculosis drugs.

Efficacy of colonoscopic re-examination across the entire colon: a randomized controlled trial.

BACKGROUND: In standard colonoscopic examinations, some polyps may be missed during the withdrawal phase. Re-examination of the right colon can improve the adenoma detection rate (ADR). However, the effectiveness of applying this re-examination strategy to the entire colon remains unknown. We investigated whether re-examination could increase the detection rate of polyps and adenomas throughout the colon. METHODS: A randomized, controlled, single-center trial (NCT03268200) was conducted in a university hospital. Patients aged 45-75 years were randomly assigned to either the study or control group. For patients in the control group, observation and polypectomy were performed once using the standard colonoscopy method. For patients in the study group, polypectomy was repeated twice during the withdrawal phase after the initial insertion of the colonoscope. These examinations were performed in the right transverse and left colons. The primary endpoints were the polyp detection rate (PDR) and ADR, defined as the proportion of patients with ≥ 1 polyp and ≥ 1 adenoma, respectively. RESULTS: Overall, 406 patients were enrolled (study group, n = 210; control group, n = 196) and analyzed. Generally, PDRs and ADRs were similar between the study (withdrawal 1 + 2) and control groups (withdrawal 1), except for the right colon. However, the second withdrawal review increased number of polyps and adenomas in the overall, right, mid, and left colon, respectively. CONCLUSION: The results of this trial indicated that re-examination of the entire colon during colonoscopy could be beneficial for detecting concealed polyps in patients at risk of interval cancer.

Cold snare polypectomy versus cold endoscopic mucosal resection for small colorectal polyps: a multicenter randomized controlled trial.

BACKGROUND: Cold snare polypectomy (CSP) is recommended for the resection of small colorectal polyps. However, few studies have investigated the efficacy of cold endoscopic mucosal resection (cold EMR) for small polyps. Thus, the aim of this study was to investigate the efficacy and safety of cold EMR compared with CSP for small colorectal polyps. METHODS: This was a multicenter, randomized trial conducted in three tertiary centers from January 2018 to February 2021. Patients with polyps sized 6-10 mm were randomized to CSP or cold EMR group. After polypectomy, two additional biopsies were performed to assess the completeness of resection. The primary outcome was complete polyp resection rate. Secondary outcomes were total procedure time and rate of adverse events such as immediate bleeding, delayed bleeding, and perforation. RESULTS: A total of 444 polyps in 327 patients were assessed and randomly assigned to each group. Of those, 425 polyps were finally analyzed based on pathology results. The complete resection rate was not significantly different between cold EMR and CSP groups (91.9% vs 89.8%, p = 0.24). However, the total procedure time was significantly increased in cold EMR (87.6 s vs. 45.8 s, p < 0.001). The rate of polypectomy adverse events was not significantly different between the two groups. No patient had massive bleeding or perforation. CONCLUSIONS: There was no difference in complete resection rate or adverse events between CSP and cold EMR. However, CSP reduced the total procedure time.

Comparison of 2 L Polyethylene Glycol Plus Ascorbic Acid and 4 L Polyethylene Glycol in Elderly Patients Aged 60-79: A Prospective Randomized Study.

BACKGROUND: The bowel-cleansing efficacy and safety of 2 L polyethylene glycol (PEG) with ascorbic acid (2L PEG + Asc) has rarely been studied in the elderly population. In this randomized trial, we compared the bowel cleanliness, safety, and tolerability of 2L PEG + Asc with those of 4 L PEG in an elderly population aged 60-79. METHODS: Study participants were randomized either to 2L PEG + Asc or 4L PEG. The primary endpoint was the success rate of bowel preparation, using the Boston Bowel Preparation Scale. Before colonoscopy, all participants were questioned about adverse events and tolerability regarding purgative ingestion. RESULTS: A total of 347 individuals were enrolled (2L PEG + Asc, 174; 4L PEG, 173). Mean age in the 2L PEG + Asc and the 4L PEG was 69.3 ± 5.6 and 69.3 ± 5.0, respectively (P = 0.917). The rate for successful bowel cleansing was comparable between the 2L PEG + Asc (92%) and the 4L PEG (96%, P = 0.118). Total ingested liquid including purgative and water was lower in the 2L PEG + Asc group (2.9 L) than in the 4L PEG group (4.2 L, P < 0.001). The tolerability of purgative was superior in the 2L PEG + Asc (overall satisfaction, P < 0.001; willingness to reuse, P < 0.001). There were no serious adverse events during the trial. CONCLUSIONS: The bowel-cleansing efficacy of 2L PEG + Asc was comparable to that of 4L PEG. Tolerability was superior in the 2L PEG + Asc group. For older people, 2L PEG + Asc is an efficacious and safe bowel cleanser. (Clinical trial registration number: KCT0004123).

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia.

AIM: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high-risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). CONCLUSION: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost-effectiveness of the various commercially available domestic HPV assays.

Propofol compared with bolus and titrated midazolam for sedation in outpatient colonoscopy: a prospective randomized double-blind study.

BACKGROUND AND AIMS: The safest and most efficient method of sedation for outpatient colonoscopy remains unclear. This study aimed to compare the efficiency and safety of bolus administration of midazolam compared with titrated administration and propofol administration for patients undergoing outpatient colonoscopy. METHODS: We randomly divided patients undergoing colonoscopy into the propofol group, bolus midazolam group, and titrated midazolam group. We compared total procedure time, induction time, recovery time, and discharge time among the 3 groups. We also compared patient satisfaction and the incidence of adverse events. RESULTS: In total, 267 patients (89 in each study group) were enrolled during the study period. Patients in the propofol group had a shorter total procedure time (39.5 vs 59.4 vs 58.1 minutes; P < .001), induction time (4.6 vs 6.3 vs 7.6 minutes; P < .001), recovery time (11.5 vs 29.5 vs 29.2 minutes; P < .001), and discharge time (20.6 vs 34.9 vs 34.7 minutes; P < .001) than patients in the bolus midazolam group and titrated midazolam group. Patients in the propofol group reported higher degrees of satisfaction than patients in the bolus or titrated midazolam plus meperidine groups (9.9 vs 9.6 vs 9.6 [P = .007] and 4.9 vs 4.7 vs 4.8 [P = .008], respectively). Adverse events were not significantly different between groups. CONCLUSIONS: In this randomized trial, propofol was superior to bolus or titrated midazolam in terms of endoscopy unit efficiency and patient satisfaction during outpatient colonoscopy. (Clinical trial registration number: KCT0002805.).

Effect of prophylactic clip application for the prevention of postpolypectomy bleeding of large pedunculated colonic polyps: a randomized controlled trial.

BACKGROUND AND AIMS: Prophylactic application of a hemoclip has been suggested as an alternative to the use of an endoloop for the prevention of postpolypectomy bleeding (PPB) when resecting large, pedunculated colorectal polyps. Therefore, this multicenter, randomized controlled trial investigated the efficacy of prophylactic hemoclip application to reduce PPB during the resection of large pedunculated polyps. METHODS: Large pedunculated polyps (≥10 mm in head diameter) were eligible for inclusion. Polyps were randomized into a study arm (where clips were applied before resection) and a control arm (without pretreatment). The primary outcome was the rate of PPB in each group. PPB included immediate PPB (IPPB) and delayed PPB (DPPB). IPPB was defined as blood oozing (≥1 minute) or active spurting occurring immediately after polyp resection. DPPB was defined as rectal bleeding, occurring after completion of the colonoscopy. RESULTS: In total, 238 polyps from 204 patients were randomized into the clip arm (119 polyps) or the control arm (119 polyps). Overall bleeding adverse events were observed in 20 cases (IPPB, 16; DPPB, 4). The rate of overall PPB, IPPB, and DPPB was 8.4%, 6.7%, and 1.7%, respectively, for all polyps. The rate of overall PPB (clip 4.2% vs control 12.6%, P = .033) and IPPB (clip 2.5% vs control 10.9%, P = .017) was significantly lower in the clip arm than the control arm. CONCLUSIONS: Prophylactic clipping before resecting large pedunculated polyps can reduce overall PPB and IPPB compared with no prior treatment. Therefore, prophylactic clipping may be considered before resection of large pedunculated polyps. (Clinical trial registration number: NCT02156193.).

Discrepancy between Cytology and Histology in Cervical Cancer Screening: a Multicenter Retrospective Study (KGOG 1040).

BACKGROUND: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells. Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. METHODS: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. RESULTS: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7 (19-88) years and mean BMI was 22.5 (16.9-34.1) kg/m². The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475-3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367-0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385-2.469). CONCLUSION: Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Comparison of bowel-cleansing efficacy of split-dose and same-day dose bowel preparation for afternoon colonoscopy in patients with gastrectomy: a prospective randomized study.

BACKGROUND: A split dose (SPD) of purgative is the recommended bowel-preparation method for colonoscopy, although for colonoscopy scheduled for the afternoon, a same-day dose (SDD) of purgative is recommended. However, it has not been determined whether SPD or SDD is better in patients with gastrectomy who are at high risk of suboptimal bowel cleansing. We compared the bowel-cleansing efficacy of SPD and SDD regimens in patients with gastrectomy who underwent colonoscopy in the afternoon. METHODS: This was a prospective, randomized, assessor-blinded study. For the SDD group, polyethylene glycol (PEG) was ingested on the day of colonoscopy starting at 7 AM. In the SPD group, 2 L PEG was ingested at 9 PM the day before colonoscopy, and the remaining 2 L from 10 AM on the day of colonoscopy. Colonoscopy was performed from 1:30 PM. Before colonoscopy, the participants completed questionnaires asking about bowel-movement kinetics, adverse events, tolerability, overall satisfaction, and willingness to reuse the protocol. The bowel-cleansing efficacy was assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 193 subjects were included (SDD, 95; SPD, 98). The rate of successful bowel cleansing was comparable between the two groups (SDD, 92.6% vs. SPD, 95.9%; P = 0.37). The incidence of adverse events (nausea, vomiting, bloating, abdominal pain, and dizziness/headache) was also comparable between the two groups. However, sleep disturbance was higher in the SPD group (SDD, 10.5% vs. SPD, 25.5%; P = 0.01). Tolerability did not differ between the SDD and SPD groups (satisfaction, P = 0.11; willingness to reuse, P = 0.29). CONCLUSIONS: The bowel-cleansing efficacy, safety profile, and patient tolerability of SDD and SPD were comparable. Both SDD and SPD regimens are feasible bowel-preparation methods for patients with gastrectomy who undergo colonoscopy in the afternoon. TRIAL REGISTRATION: Clinical trial registration number: KCT0002699.

Comparison of adenoma detection by colonoscopy between polypectomy performed during both insertion and withdrawal versus during withdrawal only: a multicenter, randomized, controlled trial.

BACKGROUND AND AIM: In standard colonoscopy, the colonoscope is inserted into the cecum, and inspection of the colonic mucosa and polypectomy are performed during withdrawal. The colon configuration can differ between the insertion and withdrawal phases, and some polyps found in the insertion phase can be missed during withdrawal. A few single-center studies investigated whether detection of polyps during the insertion phase affects the adenoma detection rate (ADR). However, the effectiveness of this strategy is unknown because of conflicting results. We aimed to determine whether polypectomy together with careful inspection during insertion increases the ADR compared with standard colonoscopy. METHODS: A randomized, controlled, multicenter trial was conducted at three university hospitals. Patients aged 50 to 80 years were randomly assigned to the study group or control group. For patients in the study group, polypectomy was performed together with careful inspection during both colonoscope insertion and withdrawal. In the control group, polyps were inspected and removed only during colonoscope withdrawal. The primary endpoint was the ADR, which was defined as the percentage of patients with ≥ 1 adenoma. RESULTS: A total of 1142 patients were enrolled (study group, n = 571; control group, n = 571). The ADR was similar in the 2 groups (study group, 44.1%; control group, 43.1%; P = 0.72). In the control group, 12 polyps that had been detected during colonoscope insertion were not found during withdrawal (polyp miss rate: 2.1%, 12/571). CONCLUSION: Polypectomy and careful inspection during both colonoscope insertion and withdrawal did not improve the overall ADR compared with standard colonoscopy (NCT01925833).

Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

Background and Purpose- Limited data are available describing the relative effectiveness, safety, and optimal dosing of non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods- Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHA2DS2-VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results- Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75-0.81 for dabigatran; HR, 0.74; 95% CI, 0.65-0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59-0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69-0.95) and apixaban (HR, 0.67; CI, 0.56-0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84-1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76-1.28) and mortality (HR, 0.85; CI, 0.62-1.16). Conclusions- In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.

Comparison of Bowel Cleansing Efficacy, Safety, Bowel Movement Kinetics, and Patient Tolerability of Same-Day and Split-Dose Bowel Preparation Using 4 L of Polyethylene Glycol: A Prospective Randomized Study.

BACKGROUND: Split-dose bowel preparation is recommended for morning colonoscopy, although a same-day dose regimen is an alternative for afternoon colonoscopy. Same-day preparation for morning colonoscopy has rarely been evaluated. OBJECTIVE: We compared the bowel cleansing efficacy, bowel movement kinetics, safety profile, and patient tolerability of split-dose and same-day preparation using 4-L polyethylene glycol. DESIGN: This was a prospective, randomized, assessor-blinded study. SETTINGS: This study was performed at a tertiary center in Korea. PATIENTS: Study subjects were randomly assigned to the same-day or split-dose groups. For the same-day dose group, 4 L of polyethylene glycol were ingested on the day of colonoscopy starting at 5:00 AM for morning colonoscopy or 7:00 AM for afternoon colonoscopy. In the split-dose group, 2 L of polyethylene glycol were ingested at 9:00 PM the day before colonoscopy, and the remaining 2 L from 7:00 AM for morning colonoscopy or from 10:00 AM for afternoon colonoscopy. Colonoscopy was performed from 10:00 AM. MAIN OUTCOME MEASURES: The efficacy of bowel cleansing was evaluated using the Boston bowel preparation scale. The participants completed questionnaires asking about adverse events, bowel movement kinetics, and tolerability of the preparation before colonoscopy. RESULTS: A total of 339 subjects were included (same-day dose = 172; split dose = 167). One subject in each group did not undergo colonoscopy. The rate of successful cleansing did not differ between the groups (same-day dose = 98.8% vs split dose = 98.2%; p = 0.681). There were no instances of hemodynamic instability or aspiration in either group. Tolerability, including overall satisfaction and willingness to reuse, were comparable between the groups. LIMITATIONS: This was a single-center study. CONCLUSIONS: The bowel cleansing efficacy, safety profile, and tolerability of same-day dosing with polyethylene glycol were comparable with those of split dose. Therefore, same-day dosing with 4 L of polyethylene glycol is a feasible bowel preparation method. See Video Abstract at http://links.lww.com/DCR/B44. COMPARACIÓN DE LA EFICACIA DE LA LIMPIEZA INTESTINAL, LA SEGURIDAD, LA CINÉTICA DEL MOVIMIENTO INTESTINAL Y LA TOLERABILIDAD DEL PACIENTE DE LA PREPARACIÓN INTESTINAL EN EL MISMO DÍA Y EN DOSIS DIVIDIDAS UTILIZANDO 4 L DE POLIETILENGLICOL: UN ESTUDIO PROSPECTIVO ALEATORIZADO: Se recomienda la preparación del intestino en dosis divididas para la colonoscopia de la mañana, aunque un régimen de una sola dosis el mismo día es una alternativa para la colonoscopia en la tarde. La preparación de una sola dosis el mismo día para la colonoscopia matutina rara vez se ha evaluado.Comparamos la eficacia de la limpieza intestinal, la cinética del movimiento intestinal, el perfil de seguridad y la tolerabilidad del paciente de la dosis dividida y la preparación el mismo día utilizando 4 L de polietilenglicol.Este fue un estudio prospectivo, aleatorizado, cegado por el evaluador.Este estudio se realizó en un centro terciario en Corea.Los sujetos del estudio fueron asignados aleatoriamente a el grupo de una dosis en el mismo día o al grupo de dosis dividida. Para el grupo de dosis del mismo día, se ingirieron 4 L de polietilenglicol el día de la colonoscopia a partir de las 5 a.m. para la colonoscopia de la mañana o las 7 a.m. para la colonoscopia de la tarde. En el grupo de dosis dividida, se ingirieron 2 L de polietilenglicol a las 9 p.m. el día anterior a la colonoscopia, y los otros 2 L restantes a partir de las 7 a.m. para la colonoscopia de la mañana o desde las 10 a.m. para la colonoscopia de la tarde. La colonoscopia se realizó a partir de las 10 a.m.La eficacia de la limpieza intestinal se evaluó mediante la escala de preparación intestinal de Boston. Los participantes completaron cuestionarios preguntando sobre los eventos adversos, la cinética del movimiento intestinal y la tolerabilidad de la preparación antes de la colonoscopia.Se incluyeron un total de 339 sujetos (dosis el mismo día, 172; dosis dividida, 167). Un sujeto en cada grupo no se sometió a colonoscopia. La tasa de limpieza exitosa no difirió entre los grupos (dosis el mismo día, 98.8% versus dosis dividida, 98.2%; p = 0.681). No hubo casos de inestabilidad hemodinámica o aspiración en ninguno de los grupos. La tolerabilidad, incluida la satisfacción general y la voluntad de reutilización, fueron comparables entre los grupos.Este fue un estudio de centro único.La eficacia de la limpieza intestinal, el perfil de seguridad y la tolerabilidad de la dosificación en el mismo día con polietilenglicol fueron comparables con los de la dosis dividida. Por lo tanto, la dosificación en el mismo día con 4 L de polietilenglicol es un método factible de preparación intestinal. Vea el video del resumen en http://links.lww.com/DCR/B44.

Treatment of benign perforations and leaks of the esophagus: factors associated with success after stent placement.

BACKGROUND: Self-expanding metal stent (SEMS) is effective and safe for the treatment of benign esophageal perforations or leaks. The purpose of this study was to identify factors associated with clinical success after SEMS placement. METHODS: Patients who received SEMS placement for treatment of benign esophageal perforations or leaks were retrospectively identified. These patients were analyzed for factors associated with clinical success and complications. RESULTS: A total of 31 patients underwent stent insertion for benign esophageal perforations (n = 11) or anastomotic leaks (n = 20). Clinical success was achieved in twenty-three patients (74.2%) after initial stent insertion. In multivariate analysis, early stent insertion within 1 day was identified as a significant independent predictor of successful sealing (Odds ratio = 3.14, 95% CI 1.36-7.24; p = 0.013). The anastomotic leak group needed a longer stent dwelling time (≥ 4 weeks) compared to the perforation group (75.0% vs. 27.3%, p = 0.022). CONCLUSIONS: Clinical success was significantly associated with early stent insertion. The dwelling time of stent was shorter for benign perforations compared to anastomotic leaks.

Increment of growth factors in mouse skin treated with non-thermal plasma.

Non-thermal plasma (NTP) has several beneficial effects, and can be applied as a novel instrument for skin treatment. Recently, many types of NTP have been developed for potential medical or clinical applications, but their direct effects on skin activation remain unclear. In this study, the effect of NTP on the alteration of mouse skin tissue was analyzed. After NTP treatment, there were no signs of tissue damage in mouse skin, whereas significant increases in epidermal thickness and dermal collagen density were detected. Furthermore, treatment with NTP increased the expression of various growth factors, including TGF-α, TGF-ß, VEGF, GM-CSF, and EGF, in skin tissue. Therefore, NTP treatment on skin induces the expression of growth factors without causing damage, a phenomenon that might be directly linked to epidermal expansion and dermal tissue remodeling.

Suppression of influenza B virus replication by sakuranetin and mode of its action.

This study aimed to investigate in vitro the anti-influenza B/Lee/40 virus effect of sakuranetin and mode of its action. The sakuranetin exhibited potent antiviral activity against influenza B/Lee/40 virus, reducing the formation of a visible cytopathic effect, with a 50% inhibitory concentration (IC50 ) of 7.21 µg/ml and no cytotoxicity at a concentration of 100 µg/ml, and the derived therapeutic index (TI) was >13.87. Oseltamivir showed weak anti-influenza B/Lee/40 virus activity with IC50 of 80.74 µg/ml, 50% cytotoxicity concentration of >100 µg/ml, and TI of >1.24. Sakuranetin also showed effective inhibitory effects when added at the viral attachment, entry, and postentry steps. Moreover, sakuranetin effectively inactivated influenza B/Lee/40 virus infection in dose- and temperature-dependent manners. Sakuranetin indicated an inhibitory effect in viral RNA synthesis in the presence of 100 µg/ml of sakuranetin. Overall, this research revealed that sakuranetin could inhibit influenza B/Lee/40 virus replication and that sakuranetin may be involved in the virus attachment, entry, and postentry. Therefore, sakuranetin is a good candidate for a chemopreventive agent for influenza virus-related diseases.

Randomized clinical trial comparing 10- or 14-day sequential therapy and 10- or 14-day concomitant therapy for the first line empirical treatment of Helicobacter pylori infection.

BACKGROUND AND AIM: Whether concomitant therapy is superior to sequential therapy (ST) as first-line therapy of Helicobacter pylori in areas with high clarithromycin resistance remains controversial. The aim of this study was to compare the efficacy and tolerability of 10- or 14-day ST with 10- or 14-day concomitant therapy (CT). METHODS: This was a prospective randomized study comparing 10- or 14-day ST with 10- or 14-day CT. The ST-10 and ST-14 groups received pantoprazole 40 mg and amoxicillin 1 g twice a day for the first 5 and 7 days followed by pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg twice a day for the remaining 5 and 7 days, respectively. The CT-10 and CT-14 groups received pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 and 14 days, respectively. RESULTS: Three hundred forty-one patients were randomly allocated to the four groups. The modified intention-to-treat eradication rates of ST-10, ST-14, CT-10, and CT-14 were 91.7%, 91.2%, 94.2%, and 98.5%, respectively. The corresponding per protocol eradication rates were 91.4%, 91.0%, 95.6%, and 98.5%. There was no difference in compliance and adverse events in the four groups. Eradication rates increased sequentially with statistical significance in the following order: ST-10, ST-14, CT-10, and CT-14 (P = 0.044). CONCLUSIONS: All four regimens achieved eradication rates >90% in per protocol analyses in a country with high clarithromycin resistance. There was no difference in tolerability among the four regimens.

Effect of Dynamic Position Changes on Adenoma Detection During Colonoscope Withdrawal: A Randomized Controlled Multicenter Trial.

OBJECTIVES: Adequate luminal distension is essential for improving adenoma detection during colonoscope withdrawal. A few crossover studies have reported that dynamic position changes maximize luminal distension and increase adenoma detection rates (ADR). We designed a multicenter, randomized, parallel-group trial to verify the effect of dynamic position changes on colonic adenoma detection. METHODS: This study was conducted at the six hospitals of the Catholic University of Korea. Patients aged 45-80 years who underwent a colonoscopy for the first time were included. In the position change group, the position changes during colonoscope withdrawal were as follows: cecum, ascending colon, and hepatic flexure: left lateral position; transverse colon: supine position; splenic flexure, descending colon, sigmoid colon, and rectum: right lateral position. In the control group, the examinations were performed entirely in the left lateral position during colonoscope withdrawal. The primary outcome measure was the ADR, which was defined as the proportion of patients with ≥1 adenoma. RESULTS: A total of 1,072 patients were randomized into the position change group (536 patients) or the control group (536 patients). The ADR was higher in the position change group than in the control group (42.4 vs. 33.0%, P=0.002). More adenomas were detected per subject in the position change group (0.90 vs. 0.67, P=0.01). Increases in the number of adenomas were observed in examinations of the transverse colon (0.22 vs. 0.13, P=0.016) and the left colon (0.37 vs. 0.27, P=0.045). A significant increase in the ADR was observed for endoscopists with a relatively low detection rate. For endoscopists with a high detection rate, non-significant changes in the ADR were observed. CONCLUSIONS: Dynamic position changes during colonoscope withdrawal increased the ADR.

Clinical outcome of endoscopic management of duodenal Dieulafoy's lesions: endoscopic band ligation versus endoscopic hemoclip placement.

BACKGROUND: The most appropriate type of endoscopic hemostasis for bleeding due to duodenal Dieulafoy's lesions (DLs) is not yet established. The aim of this study was to assess the efficacy of mechanical endoscopic hemostasis for duodenal DLs and long-term outcome after successful hemostasis, as well as to compare the efficacy and safety of endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP). METHODS: Patients admitted to the emergency unit with acute upper gastrointestinal bleeding from duodenal DLs were enrolled in this study. The data were collected prospectively, but data analysis was performed retrospectively. Twenty-four patients with duodenal DLs were treated with EBL (n = 11) or EHP (n = 13). RESULTS: There were no significant differences between groups with respect to clinical or endoscopic characteristics, apart from the number of epinephrine (three cases with EBL vs. 11 cases with EHP; p = 0.011). Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient (9.1 %) from the EBL group and in five patients (38.5 %) from the EHP group (p = 0.166). The recurrent bleeding in the patient from the EBL group was treated by EHP. In the EHP group, all five patients achieved successful secondary hemostasis by endoscopic treatment (EBL in two patients and EHP in three patients). There were no differences in secondary outcomes between the two groups, including the number of endoscopic sessions required, need for angiographic embolization or emergent surgery, transfusion requirements, or length of hospital stay. No complications occurred, and there was no recurrence of bleeding in either group during the follow-up period. CONCLUSIONS: Mechanical endoscopic treatments are effective and safe for the treatment of bleeding duodenal DLs. A large-scale, randomized, controlled study is required to confirm the efficacy and safety of EBL and EHP for the management of bleeding duodenal DLs.