Alan Kawarai Lefor

Favipiravir: A New Medication for the Ebola Virus Disease Pandemic

The purpose of this report is to advocate speedy approval and less stringent regulations for the use of experimental drugs such as favipiravir in emergencies. Favipiravir is a new antiviral medication that can be used in emerging viral pandemics such as Ebola virus, 2009 pandemic influenza H1N1 virus, Lassa fever, and Argentine hemorrhagic fever. Although favipiravir is one of the choices for the treatment of patients with Ebola virus, several concerns exist. First, a clinical trial of favipiravir in patients infected with the Ebola virus has not yet been conducted, and further studies are required. Second, favipiravir has a risk for teratogenicity and embryotoxicity. Therefore, the Ministry of Health, Welfare and Labor of Japan has approved this medication with strict regulations for its production and clinical use. However, owing to the emerging Ebola virus epidemic in West Africa, on August 15, 2014, the Minister of Health, Welfare and Labor of Japan approved the use of favipiravir, if needed.

Long-term Outcomes in Patients with Small Intestinal Strictures Secondary to Crohn's Disease After Double-balloon Endoscopy-assisted Balloon Dilation.

Background:Crohns disease (CD) strictures of the small intestine are a feared complication and difficult to treat because of difficulty gaining access to the stricture site. The development of double-balloon endoscopy (DBE) enabled access to the entire small intestine with interventional capabilities. The aim of this study was to assess the long-term outcomes in patients with small intestinal strictures secondary to CD after DBE-assisted endoscopic balloon dilation (EBD). Methods:In this retrospective cohort study, DBE-assisted EBD was performed in 85 consecutive patients with CD strictures of the small intestine from 2002 to 2014. Follow-up data were available for 85 patients for a mean of 41.9 months (range, 0–141), and clinical outcomes were assessed. Results:Overall, 321 DBE-assisted EBD sessions (473 procedures) were performed in 85 patients during the study period. Most CD strictures were de novo (97%). The surgery-free rate after initial DBE-assisted EBD was 87.3% at 1 year and 78.1% at 3 years. The presence of a fistula was significantly associated with the need for surgical intervention (hazard ratio = 5.50, 95% confidence interval: 2.16–14.0, P < 0.01). The surgery-free interval in patients with a fistula was significantly shorter than in patients without a fistula (P < 0.01, log-rank test). Conclusions:DBE-assisted EBD provides a favorable long-term outcome in patients with small intestinal CD-associated strictures. DBE-assisted EBD for CD strictures is a safe and effective treatment to avoid or postpone surgery over the long-term.

Pocket-creation method facilitates endoscopic submucosal dissection of colorectal laterally spreading tumors, non-granular type

Background and study aims The pocket-creation method (PCM) is a novel strategy for endoscopic submucosal dissection (ESD). The aim of this study is to determine the efficacy of the PCM for colorectal laterally spreading tumors, non-granular type (LST-NG). Patients and methods The records of 126 consecutive patients with colorectal LST-NG who underwent ESD between April 2012 and July 2015 were retrospectively reviewed. Patients were divided into PCM (n = 73) and conventional method (CM) (n = 53) groups. Results The en bloc resection rate in the PCM group was significantly higher than in the CM group (100 % [73/73] vs. 92 % [49/53], P = 0.03). The en bloc resection rate with severe fibrosis was higher in the PCM group than in the CM group (100 % [3/3] vs. 60 % [3/5]). The R0 resection rate for the two groups was not statistically significantly different (93 % [68/73] vs. 91 % [48/53], P = 0.74). The perforation rate in the PCM group was lower than in the CM group although not statistically significantly less (0 % 0/73 vs. 4 % 2/53, P = 0.18). For lesions resected en bloc, dissection speed for the PCM group was significantly faster than for the CM group (median [IQR], 19 [13 –24] vs. 14 [10 – 22] mm2/min, P = 0.03). Conclusion ESD using PCM achieves a reliable and safe resection of colorectal LST-NG.

Duodenal endoscopic submucosal dissection is feasible using the pocket-creation method

Background and study aims Duodenal endoscopic submucosal dissection (ESD) requires sophisticated endoscopic techniques because of a high rate of perforation. We introduced the pocket-creation method (PCM) of duodenal ESD to overcome difficulties. The aim of this study was to evaluate the safety and usefulness of ESD using the PCM for superficial tumors of the duodenum. Patients and methods We performed ESD of 17 non-ampullary duodenal lesions using the conventional method and of 28 lesions using the PCM from 2006 to 2015 and retrospectively reviewed the results, comparing the PCM and the conventional method. The median follow-up period was 35 months (range 2 - 97). Results There were more lesions at the duodenal angles in the PCM group compared with the conventional method group (54 % [15/28] vs. 22 % [4/17]; P = 0.048), and the resected specimen diameter was larger in the PCM than the conventional method group (median 37 mm [range 25 - 101] vs. 25 mm [15 - 55]; P = 0.007). Dissection speed was faster in the PCM than the conventional method group (9.4 mm2/min [3.0 - 15.7] vs. 6.5 mm2/min [1.5 - 19.7]; P = 0.09). En bloc resection was more frequent in the PCM (100 % [28/28]) than the conventional method group (88 % [15/17]) (P = 0.07). Perforation was significantly less frequent in the PCM (7 % [2/28]) than the conventional method group (29 % [5/17]; P = 0.046). The one delayed perforation in the conventional method group required surgical repair, while other intraprocedural perforations were treated by clipping. There were no recurrences. Conclusions ESD of duodenal lesions can be safely performed using the PCM, which stabilizes the tip of the endoscope even in difficult locations.

Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium‐competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid‐suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention‐to‐treat (ITT) analysis and 76% (419/549) of patients in per‐protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy.

Efficacy and safety of endoscopic submucosal dissection for superficial colorectal tumors more than 50 mm in diameter.

BACKGROUND AND AIMS The feasibility of endoscopic submucosal dissection (ESD) for large superficial colorectal tumors is undefined. The aim of this study was to assess the outcomes for patients undergoing ESD of superficial colorectal tumors larger than 50 mm. METHODS A total of 472 patients who underwent ESD for superficial colorectal tumors from 2010 to 2014 were enrolled. We retrospectively reviewed their records. RESULTS We compared patients with 20-mm to 50-mm lesions and those with lesions >50 mm regarding demographics, the ESD procedure, and histopathology. Among patients with lesions >50 mm, laterally spreading tumors nongranular and protruded types were uncommon. Histopathologically, deeply invasive (≥1000 μm) submucosal carcinomas were more frequent in lesions >50 mm (14% [10/70] vs 5% [20/402], P < .01). Technically, en bloc resection was successfully accomplished in 99% of patients (69/70). Although the total dissection time for lesions >50 mm was significantly longer than for lesions 20 mm to 50 mm (mean ± SD, 157 ± 114 minutes vs 68 ± 50 min; P < .01), dissection speed for lesions >50 mm was significantly faster than for lesions 20 mm to 50 mm (P < .01). There were no significant differences in en bloc R0 resection rate comparing both groups (>50 mm, 83% vs 20 mm to 50 mm, 87%; P = .31). No perforations or postoperative bleeding occurred in patients with lesions >50 mm. Post-ESD colorectal strictures requiring intervention did not develop in any patient. CONCLUSIONS ESD for superficial colorectal tumors >50 mm is feasible. ESD of these lesions had a high R0 resection rate and a low adverse event rate. En bloc resection by ESD provides adequate pathological specimens and may limit the need for surgical intervention.

The Volume-Outcome Relationship in Critically Ill Patients in Relation to the ICU-to-Hospital Bed Ratio.

Objectives:A volume-outcome relationship in ICU patients has been suggested in recent studies. However, it is unclear whether the ICU-to-hospital bed ratio affects the volume-outcome relationship. The aim of this study is to investigate the relationship between hospital volume and in-hospital mortality of adult ICU patients in relation to the ratio of ICU beds to regular hospital beds. Design:Retrospective cohort study. Setting:Four hundred seventy-seven Japanese hospitals from 2007 to 2012 in the Japanese Diagnosis Procedure Combination database. Patients:A total of 596,143 patients discharged from acute care hospitals. Interventions:None. Measurements and Main Results:We analyzed data from 596,143 ICU patients from 2007 through 2012 using a nationwide administrative database. Patients were categorized into nine subgroups (the tertiles of hospital volume of ICU patients combined with the tertiles of ICU-to-hospital bed ratio). Multivariable logistic regression analyses were performed to examine the concurrent effects of hospital volume of ICU patients and ICU-to-hospital bed ratio on in-hospital mortality, with adjustment for patient and hospital characteristics. Higher hospital volume of ICU patients and a higher ICU-to-hospital bed ratio were independently associated with lower mortality. When patients were stratified by ICU-to-hospital bed ratio categories, in-hospital mortality was significantly lower in the high-volume subgroup (odds ratio, 0.74; 95% CI, 0.58–0.93) compared with the low-volume subgroup in hospitals with a high ICU-to-hospital bed ratio. However, these relationships were not significant in hospitals with low ICU-to-hospital bed ratios (odds ratio, 0.94; 95% CI, 0.59–1.50) or in hospitals with intermediate ICU-to-hospital bed ratios (odds ratio, 0.80; 95% CI, 0.71–1.08). Conclusions:An inverse relationship between hospital volume of ICU patients and mortality was seen only when the ICU-to-hospital bed ratio was sufficiently high. Regionalization and increasing the number of ICU beds in referral centers may improve patient outcomes.

Gastrografin as an alternative booster to sodium phosphate in colon capsule endoscopy: safety and efficacy pilot study.

Background and study aims: Sodium phosphate is a key component of bowel preparation regimen for colon capsule endoscopy (CCE), but may cause serious complications. The aim of this study is to evaluate the use of Gastrografin, substituted for sodium phosphate, in CCE bowel preparation. Patients and methods: In total, 29 patients (median age 64 years; 23 females) underwent CCE, covered by the national health insurance system of Japan. All had a history of laparotomy and/or previously incomplete colonoscopy. On the day before examination, patients ingested 1 L of polyethylene glycol + ascorbic acid with 0.5 L of water in the evening, and again the same laxative on the morning of examination. After capsule ingestion, 50 mL of Gastrografin diluted with 0.9 L of magnesium citrate was administered, and then repeated after 1 hour. Results: The capsule excretion rate was 97 % (28/29). The median colon transit time was 2 hours 45 minutes and rapid transit (< 40 minutes) through the colon occurred in one patient (3.4 %). Bowel cleansing level was adequate in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. Diluted Gastrografin was well tolerated by patients. No adverse events occurred. Conclusion: Gastrografin can be an alternative to sodium phosphate in CCE bowel preparation regimen.

Arcuate Na+,K+-ATPase senses systemic energy states and regulates feeding behavior through glucose-inhibited neurons

Feeding is regulated by perception in the hypothalamus, particularly the first-order arcuate nucleus (ARC) neurons, of the bodys energy state. However, the cellular device for converting energy states to the activity of critical neurons in ARC is less defined. We here show that Na(+),K(+)-ATPase (NKA) in ARC senses energy states to regulate feeding. Fasting-induced systemic ghrelin rise and glucose lowering reduced ATP-hydrolyzing activity of NKA and its substrate ATP level, respectively, preferentially in ARC. Lowering glucose concentration (LG), which mimics fasting, decreased intracellular NAD(P)H and increased Na(+) concentration in single ARC neurons that subsequently exhibited [Ca(2+)]i responses to LG, showing that they were glucose-inhibited (GI) neurons. Third ventricular injection of the NKA inhibitor ouabain induced c-Fos expression in agouti-related protein (AgRP) neurons in ARC and evoked neuropeptide Y (NPY)-dependent feeding. When injected focally into ARC, ouabain stimulated feeding and mRNA expressions for NPY and AgRP. Ouabain increased [Ca(2+)]i in single NPY/AgRP neurons with greater amplitude than in proopiomelanocortin neurons in ARC. Conversely, the specific NKA activator SSA412 suppressed fasting-induced feeding and LG-induced [Ca(2+)]i increases in ARC GI neurons. NPY/AgRP neurons highly expressed NKAα3, whose knockdown impaired feeding behavior. These results demonstrate that fasting, via ghrelin rise and LG, suppresses NKA enzyme/pump activity in ARC and thereby promotes the activation of GI neurons and NPY/AgRP-dependent feeding. This study identifies ARC NKA as a hypothalamic sensor and converter of metabolic states to key neuronal activity and feeding behaviour, providing a new target to treat hyperphagic obesity and diabetes.

Diagnostic Performance and Patient Acceptance of Reduced-Laxative CT Colonography for the Detection of Polypoid and Non-Polypoid Neoplasms: A Multicenter Prospective Trial

Purpose To evaluate the diagnostic accuracy and patient acceptance of reduced-laxative computed tomographic (CT) colonography without computer-aided detection (CAD) for the detection of colorectal polypoid and non-polypoid neoplasms in a population with a positive recent fecal immunochemical test (FIT). Materials and Methods Institutional review board approval and written informed consent were obtained. This multicenter prospective trial enrolled patients who had positive FIT results. Reduced-laxative CT colonography and colonoscopy were performed on the same day. Patients received 380 mL polyethylene glycol solution, 20 mL iodinated oral contrast agent, and two doses of 20 mg mosapride the day before CT colonography. The main outcome measures were the accuracy of CT colonography for the detection of neoplasms 6 mm or larger in per-patient and per-lesion analyses and a survey of patient perceptions regarding the preparation and examination. The Clopper-Pearson method was used for assessing the 95% confidence intervals of per-patient and per-lesion accuracy. Survey scores were analyzed by using the Wilcoxon and χ2 tests. Results Three hundred four patients underwent both CT colonography and colonoscopy. Per-patient sensitivity, specificity, positive predictive value, and negative predictive value of CT colonography for detecting neoplasms 10 mm or larger were 0.91 (40 of 44), 0.99 (255 of 258), 0.93 (40 of 43), and 0.98 (255 of 259), respectively; these values for neoplasms 6 mm or larger were 0.90 (71 of 79), 0.93 (207 of 223), 0.82 (71 of 87), and 0.96 (207 of 215), respectively. Per-lesion sensitivities for detection of polypoid and non-polypoid neoplasms 10 mm or larger were 0.95 (40 of 42) and 0.67 (six of nine), respectively; those for neoplasms 6 mm or larger were 0.90 (104 of 115) and 0.38 (eight of 21), respectively (P < .05 for both). Patient acceptance of preparation and examination with CT colonography was significantly higher than that with colonoscopy, and 62% (176 of 282) of patients would choose CT colonography as the first examination if they have a positive FIT result in the future. Conclusion Reduced-laxative CT colonography without CAD is accurate in the detection of polypoid neoplasms 6 mm or larger but is less accurate in the detection of non-polypoid neoplasms. Reduced-laxative CT colonography has high patient acceptance and is an efficient triage examination for patients with a positive FIT.