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Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae spp., MDR or extensively drug-resistant (XDR)-Acinetobacter baumannii complex spp., followed by Stenotrophomonas maltophilia, Chryseobacterium indologenes, and Elizabethkingia meningoseptica are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the Klebsiella pneumoniae carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-P. aeruginosa or A. baumannii complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.

Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society.

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Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

Glycine N-methyltransferase (GNMT) is a folate binding protein commonly diminished in human hepatoma yet its role in tumor development remains to be established. GNMT binds to methylfolate but is also inhibited by it; how such interactions affect human carcinogenesis is unclear. We postulated that GNMT plays a role in folate-dependent methyl group homeostasis and helps maintain genome integrity by promoting nucleotide biosynthesis and DNA repair. To test the hypothesis, GNMT was over-expressed in GNMT-null cell lines cultured in conditions of folate abundance or restriction. The partitioning of folate dependent 1-carbon groups was investigated using stable isotopic tracers and GC/MS. DNA damage was assessed as uracil content in cell models, as well as in Gnmt wildtype (Gnmt 1/1 ), heterozygote (Gnmt) and knockout (Gnmt 2/2 ) mice under folate deplete, replete, or supplementation conditions. Our study demonstrated that GMMT 1) supports methylene-folate dependent pyrimidine synthesis; 2) supports formylfolate dependent purine syntheses; 3) minimizes uracil incorporation into DNA when cells and animals were exposed to folate depletion; 4) translocates into nuclei during prolonged folate depletion.In conclusion, loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. To our best knowledge, the role of GNMT in folate dependent 1-carbon transfer in nucleotide biosynthesis has never been investigated. The present study gives new insights into the underlying mechanism by which GNMT can participate in tumor prevention/suppression in humans.

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BackgroundThe indication of retroperitoneal laparoscopic adrenalectomy (RLA) was extended with the retroperitoneal approach and has been wildly accepted and technologically matured. However, the management of large adrenal tumors via this approach still remains controversial. The aim of this study was to perform a comprehensive analysis on the minimally invasive surgical management of larger adrenal tumors.MethodsA total of 78 patients with large adrenal tumors (> 5 cm) and 97 patients with smaller adrenal tumors (< 5 cm) were enrolled in this study. The patient characteristics were preferentially analyzed. The intra-operative and postoperative indicators were compared between those who underwent RLA and those who underwent transperitoneal laparoscopic adrenalectomy (TLA); the intra-operative and postoperative indicators were also compared between the large tumor group and smaller tumor group of those who underwent RLA. Furthermore, the analyses of partial RLA were focused on the perioperative indicators and follow-up results.ResultsRLA was superior to TLA in terms of operation time (98.71 ± 32.30 min vs. 124.36 ± 34.62 min, respectively, P = 0.001), hospitalization duration (7.43 ± 2.82 days vs. 8.91 ± 3.40 days, respectively, P = 0.04), duration of drain (4.83 ± 0.37 days vs. 3.94 ± 2.21 days, respectively, P = 0.02), first oral intake (2.82 ± 0.71 days vs. 1.90 ± 0.83 days, respectively, P < 0.001) and time to ambulation (3.89 ± 1.64 days vs. 2.61 ± 1.42 days, respectively, P < 0.001). Further analyses of the RLA patients demonstrated that the larger tumor (> 5 cm) group showed superior results for the intraoperative indicators than the smaller tumor (< 5 cm) group (P < 0.05), while the results for the postoperative indicators between the two tumor size groups were similar (P > 0.05). Data confirmed that the partial resection method was superior to the total resection method from the perspective of the hormone supplement (0% vs. 48.15%, P = 0.002). The 2-year recurrence-free rates were 92.60 and 92.86% for the total and partial RLA resection methods, respectively (P = 0.97). The partial RLA resection method had a similar complete remission rate as the total RLA resection method (96.30% vs. 100%, respectively, P = 0.47).ConclusionBoth RLA and TLA seem to provide similar effects for the surgical management of large adrenal tumors. However, partial RLA resection should be considered for the management of benign tumors to reduce the hormone supplement.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0349-0) contains supplementary material, which is available to authorized users.