Post-marketing Surveillance of a Quadrivalent Influenza Vaccine (Vaxigrip Tetra) in South Korea.

INTRODUCTION: In 2017, a quadrivalent inactivated split-virion influenza vaccine (QIV; Vaxigrip Tetra®, Sanofi) was licensed in South Korea for active immunization against influenza A and influenza B viruses in individuals aged 3 years or older, which was subsequently extended to individuals aged 6 months or older in 2018. Post-marketing surveillance trials are mandatory in South Korea to retain drug licensure. Here, we assessed the safety of QIV in routine clinical practice in South Korea. METHODS: This was an open, multicenter, observational, active safety surveillance study conducted between 20 June 2017 and 19 June 2021 at 10 study sites in South Korea in individuals aged 3 years or older who received a single dose of QIV during a routine healthcare visit. The participants or their legally acceptable representatives were instructed to record any adverse reactions (solicited events) and unsolicited non-serious adverse events (AE) in diary cards, and notify study investigators in case of serious adverse events (SAE). RESULTS: Overall, 663 participants were included in this study. There were no AEs leading to study termination, and no SAEs reported. Injection site pain (278 [41.9%]) was the most frequent solicited injection site reaction, with myalgia (250 [37.7%]) and malaise (236 [35.6%]) the most frequent solicited systemic reactions. Grade 3 solicited injection site and systemic reactions were reported by 8 (1.2%) and 13 (2.0%) participants, respectively; most participants with solicited reactions recovered without the need for further action. Overall, 39 (5.9%) participants experienced 49 unsolicited non-serious AEs with the most frequently reported being nasopharyngitis (19 [2.9%]). Grade 3 unsolicited non-serious adverse events were reported in 1 (0.2%) participant. None of the unsolicited non-serious AEs were considered to be related to QIV. CONCLUSION: This post-marketing surveillance study confirms that QIV is well tolerated and has an acceptable safety profile in routine practice in South Korea. No unexpected safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05406180.

Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy-proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence-based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm. METHODS: This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy-evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high-grade dysplasia or adenocarcinoma. RESULTS: Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy-proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low-grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12-3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01-7.87; P = 0.049). CONCLUSIONS: The presence of biopsy-proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early.

Stress and sleep quality in doctors working on-call shifts are associated with functional gastrointestinal disorders.

AIM: To investigate the role of sleep quality and psychosocial problems as predictors of functional gastrointestinal disorders (FGIDs) in doctors that work 24 hour-on-call shifts. METHODS: In this cross-sectional observation study, using the Rome III Questionnaire and Pittsburgh Sleep Quality Index (PSQI), we analyzed 170 doctors with 24 hour-on-call shifts. RESULTS: Among the participants that had experienced a 24 hour-on-call shift within the last 6 mo, 48 (28.2%) had FGIDs. Overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 16.5% and 17.1%, respectively, with 5.3% exhibiting both. Sleep scores (PSQI) (8.79 ± 2.71 vs 7.30 ± 3.43, P = 0.008), the presence of serious psychosocial alarm (83.3% vs 56.6%, P = 0.004), and the proportion of doctors who experienced over two months of recent on-call work (81.2% vs 68.9%, P = 0.044) were significantly different between individuals with or without FGIDs. Multivariate analysis revealed that presenting serious psychosocial alarm was an independent risk factor for prevalence of FD (OR = 5.47, 95%CI: 1.06-28.15, P = 0.042) and poor sleep quality (PSQI ≥ 6) was a predictor of IBS (OR = 4.17, 95%CI: 1.92-19.02, P = 0.016). CONCLUSION: Physicians should recognize the role of sleep impairment and psychological stress in the development of FGIDs and a comprehensive approach should be considered to manage patients with FGIDs.

The Loop-Tip Wire for Selective Cannulation during ERCP in Patients with Billroth II Anastomosis: A Preliminary Feasibility Study.

BACKGROUND/AIMS: Selective cannulation of common bile duct remains technically challenging in patients with Billroth II anastomosis due to an altered anatomy. We aimed to determine the feasibility of performing wire-assisted cannulation using a loop-tip wire during ERCP in patients with Billroth II anastomosis. METHODOLOGY: We retrospectively analyzed a database of nine patients with Billroth II anastomosis who underwent ERCP using a loop-tip wire from January 2009 to July 2013 in the Hallym University Sacred Heart Hospital. Clinical characteristics and procedure-associated clinical outcomes were analyzed. RESULTS: The mean age of the patients was 73.7 years, and the male/female ratio was 2:1. The success rate of selective biliary cannulation was 77.8%. The mean cannulation time was 3.6 minutes (range, 1-9 minutes). Two patients who had failed in selective cannulation underwent infundibulotomy using a needle-knife papillotome, but one of the two patients had failed in biliary stone removal and finally underwent surgery. Six patients underwent endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in seven patients in one session. There was one case of mild post-ERCP pancreatitis (11.1%). CONCLUSIONS: The loop-tip wire can be an alternative instrument for wire-assisted selective cannulation in patients with Billroth II anastomosis.

[Changes in serum vitamin D assay usage and the need for evidence-based recommendations]. / Évolution des dosages sériques de vitamine D dans un hôpital d'adultes Plaidoyer pour l'élaboration de recommandations en vue d'une juste prescription.

Result of renewed interest due to the large amount of literature that reported numerous epidemiological data demonstrating the high prevalence of vitamin D deficiency, the number of prescriptions of serum vitamin D assays has grown exponentially in recent years with a cost for health insurance that increased almost fivefold in four years. The quantitative and qualitative analysis of assays carried out from 2007 to 2011 in a French university adult short-stay hospital shows changes in practices not only quantitatively but also qualitatively resulting in an overtime increase in the frequency of prescriptions in patients younger, less vitamin D deficient and more frequently male. In the absence of French guidelines, this development cannot be qualified as deviant but justifies the urgent need to establish evidence-based recommendations for good prescriptions and adequate assays of blood vitamin D.

Inhibition of FGF signaling converts dorsal mesoderm to ventral mesoderm in early Xenopus embryos.

In early vertebrate development, mesoderm induction is a crucial event regulated by several factors including the activin, BMP and FGF signaling pathways. While the requirement of FGF in Nodal/activin-induced mesoderm formation has been reported, the fate of the tissue modulated by these signals is not fully understood. Here, we examined the fate of tissues when exogenous activin was added and FGF signaling was inhibited in animal cap explants of Xenopus embryos. Activin-induced dorsal mesoderm was converted to ventral mesoderm by inhibition of FGF signaling. We also found that inhibiting FGF signaling in the dorsal marginal zone, in vegetal-animal cap conjugates or in the presence of the activin signaling component Smad2, converted dorsal mesoderm to ventral mesoderm. The expression and promoter activities of a BMP responsive molecule, PV.1 and a Spemann organizer, noggin, were investigated while FGF signaling was inhibited. PV.1 expression increased, while noggin decreased. In addition, inhibiting BMP-4 signaling abolished ventral mesoderm formation induced by exogenous activin and FGF inhibition. Taken together, these results suggest that the formation of dorso-ventral mesoderm in early Xenopus embryos is regulated by a combination of FGF, activin and BMP signaling.

Plasma homocysteine measurement with ion exchange chromatography (Jeol Aminotac 500): a comparison with the Abbott IMx assay.

OBJECTIVE: We evaluated ion exchange chromatography (IEC) on the Jeol Aminotac 500 analyzer for total homocysteine (tHcy) determination and compared it with an immunoassay method using fluorescence polarization on an Abbott IMx analyzer. METHODS: IEC method validation (linearity, limit of detection, precision, interference) was made according to the French Biology Society guidelines (Société Française de Biologie Clinique). Moreover, during a 2-month period, 55 plasma samples from patients scheduled for routine tHCy measurement were assayed by both methods for determining correlation. RESULTS: The IEC method was found linear up to at least 190 micromol/l, and the limit of detection was 1.6 micromol/l. Precision was studied with 3 controls at 6, 15 and 30 micromol/l. Intra-assay coefficients of variation (n = 14) were 8.3, 3.1 and 2.3%, respectively, and inter-assay coefficients of variation (n = 15) were 9.6, 5.1 and 4.9%, respectively. No interference was found with other sulfur-containing amino acids (methionine, cysteine). An excellent agreement was found between IEC and fluorescence polarization (Deming regression; y = 0.99x - 1.23; r = 0.97; p < 0.001). CONCLUSION: The IEC method for tHcy measurement shows adequate precision and correlates highly with the IMx assay. The IEC method is more time-consuming but less expensive in reagent cost and allows simultaneous determination of plasma methionine concentration which may help to explain the underlying mechanism responsible for hyperhomocysteinemia.

Identification and characterization of murine mHAUSP encoding a deubiquitinating enzyme that regulates the status of p53 ubiquitination.

Recently, it was discovered that herpesvirus-associated ubiquitin-specific protease (HAUSP) in human interacts with p53 protein, and removes the ubiquitin from ubiquitinated p53. Thus, human HAUSP stabilizes the status of p53, induces p53-dependent cell growth repression and apoptosis. In this study, we isolated and characterized a mouse orthologue of HAUSP, mHAUSP. The mHAUSP cDNA was cloned from mouse ES cells by RT-PCR. The open reading frame consists of 3,312 bp and encodes a predicted protein of 1,103 amino acids with a molecular weight of approximately 135 kDa. The N-terminal region contains the Cys, His, and Asp domains, which are highly conserved in all deubiquitinating enzymes. Northern blot analysis revealed that two transcripts were detected in various tissues, with strong expression in brain, lung, thymus, and testis. In vivo and in vitro deubiquitinating enzyme assays demonstrated that mHAUSP has deubiquitinating enzyme activity. The overexpression of mHAUSP reduces the amount of ubiquitinated p53, indicating that it functions as a deubiquitinating enzyme for p53.