ArmA and RmtB Were the Predominant 16S RMTase Genes Responsible for Aminoglycoside-resistant Isolates in Korea

Pathogenic gram-negatives that produce 16S ribosomal RNA methyltransferases (16S RMTases) have already been distributed all over the world. To investigate the predominance of aminoglycoside resistance associated with 16S RMTases in Korea, we collected a total of 222 amikacin resistant Gram-negative clinical isolates from patient specimens between 1999 and 2015 from three hospital banks across Korea. ArmA and nntB were the predominant 16S RMTase genes responsible for aminoglycoside-resistant isolates circulating in Korean community settings although only one rmtA-producing isolate was detected in 2006.1

Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study

Background To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles. Objective To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES. Methods In this prospective randomized case–control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2–3weeks (minimal session: 7 times, treatment duration: 300–800min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale. Results The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores. Conclusions The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia. Trial registration: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1 .This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI18C1169). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Min‑ istry of Science, ICT and Future Planning (NRF- NRF-2016R1D1A1B03935130)

Reproduction of Gastric Cancer Prognostic Score by real-time quantitative polymerase chain reaction assay in an independent cohort

Purpose Addition of molecular markers to the American Joint Committee on Cancer (AJCC) staging system would allow further refinements in predicting recurrence and help individualize treatment decisions. We aimed to validate the Gastric Cancer Prognostic Score (GCPS) in an independent cohort using an easy and cost effective quantitative real-time polymerase chain reaction (qRT-PCR) assay. Methods We performed qRT-PCR using 48 samples from our previous study and expanded to 128 independent patients. The GCPS was recalculated using Cox regression estimates and the performance of cutoff values for GCPS was reassessed. Results The qRT-PCR results showed a similar pattern to nanostring data by scale function data comparison. Using a new cutoff value, GCPS stratified 95 stage IB–III patients who received adjuvant chemotherapy into 74 high-risk patients and 21 low-risk patients with significantly different recurrence-free survival (P< 0.0001). The survival difference remained significant (P= 0.028) in 27 patients who did not receive adjuvant chemotherapy. Among stage I and II patients who were treated with surgery only, one AJCC stage IIA patient was defined as low-risk and showed long-term survival. Nine of 12 high-risk patients showed recurrence less than 67 months after operation. Conclusion We reproduced the GCPS with an easily applicable qRT-PCR assay and successfully predicted recurrence in patients with gastric cancer

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Treatment outcomes of gonadotropin-releasing hormone agonist in obese girls with central precocious puberty

Purpose This study investigated the influence of obesity on the clinical course and effect of gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP). Methods Medical records of 182 girls with CPP treated with GnRHa were reviewed. They were divided into 2 groups: normal weight (n=108) and overweight/obesity (n=74). Chronological age (CA), bone age (BA), difference between BA and CA (BA–CA), standard deviation score (SDS) of height, body mass index (BMI), predicted adult height (PAH), and laboratory findings were compared at baseline, after 1 year, and at the end of GnRHa treatment in both groups. Results Mean BMI SDS at baseline was 0.08±0.60 in the normal weight group and 1.55±0.36 in the overweight/obesity group. Initial CA, BA, midparental height, and PAH were similar between the 2 groups. BA–CA after treatment was significantly decreased compared to baseline in both groups (P<0.001). Between the 2 groups, a decrease in BA–CA during treatment showed no significant difference. PAH at the end of treatment was significantly increased compared to baseline in both groups (P<0.001). PAH at the end of treatment in the overweight/obesity group (159.88±3.41 cm) was similar to that of the normal weight group (159.19±3.25 cm). Comparing the 2 groups according to change in BMI after treatment, there were no differences in ΔPAH, ΔBA–CA, and Δheight SDS for BA. Conclusions GnRHa treatment in obese girls with CPP improved the height outcome and had similar results in normal weight CPP girls. Obesity might not affect the efficacy of GnRHa in girls with CPP