Programmed Chemotherapy for Patients with Metastatic Unresectable Gastric Cancer

BACKGROUND: Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. CONCLUSIONS/SIGNIFICANCE: This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Methylobacterium Species Promoting Rice and Barley Growth and Interaction Specificity Revealed with Whole-Cell Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) Analysis.

Methylobacterium species frequently inhabit plant surfaces and are able to utilize the methanol emitted from plants as carbon and energy sources. As some of the Methylobacterium species are known to promote plant growth, significant attention has been paid to the mechanism of growth promotion and the specificity of plant-microbe interactions. By screening our Methylobacterium isolate collection for the high growth promotion effect in vitro, we selected some candidates for field and pot growth tests for rice and barley, respectively. We found that inoculation resulted in better ripening of rice seeds, and increased the size of barley grains but not the total yield. In addition, using whole-cell matrix-assister laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) analysis, we identified and classified Methylobacterium isolates from Methylobacterium-inoculated rice plants. The inoculated species could not be recovered from the rice plants, and in some cases, the Methylobacterium community structure was affected by the inoculation, but not with predomination of the inoculated species. The isolates from non-inoculated barley of various cultivars grown in the same field fell into just two species. These results suggest that there is a strong selection pressure at the species level of Methylobacterium residing on a given plant species, and that selection of appropriate species that can persist on the plant is important to achieve growth promotion

Growth of <i>Methylobacterium</i>-inoculated barley.

<p>The data are presented as mean ± standard deviation, and analyzed with one-way ANOVA and Dunnett’s test. Statistical significance was indicated with</p><p>* (<i>p</i> < 0.05),</p><p>** (<i>p</i> < 0.01),</p><p>*** (<i>p</i> < 0.001),</p><p>**** (<i>p</i> < 0.0001).</p><p>Growth of <i>Methylobacterium</i>-inoculated barley.</p

Maximum-likelihood phylogenetic tree of <i>Methylobacterium</i> isolates and related taxa, based on 16S rRNA gene sequences.

<p>Isolates from rice are colored in green and those from barley are in blue. Numbers in parentheses indicate isolates belonging to the same species, estimated by WC-MS analysis. For isolates from rice, the inoculation effect is not taken into account in the figure. <i>M aquaticum</i> strain 22A is taken as a representative strain for the <i>M</i>. <i>platani/aquaticum</i> cluster shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129509#pone.0129509.g001" target="_blank">Fig 1</a>. Bootstrap percentages based on 1000 replicates are shown if greater than 80%. <i>Microvirga flocculans</i> TFB (AB098515) was used as an outgroup. Bar, 0.1 changes per nucleotide position.</p

MSP dendrogram based on WC-MS analysis of the isolates from leaves of inoculated rice seed.

<p>The isolates were named with the treated strain name and isolate numbers. The inoculated strains are colored in red. The representatives selected from each cluster are colored in blue with the closest type strain name and percentage identity of 16S RNA gene in parentheses. Isolate 22A-9 was pink-pigmented fungus and was identified by ITS region sequencing, as described previously [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129509#pone.0129509.ref019" target="_blank">19</a>].</p

MSP dendrogram based on WC-MS analysis of the isolates from barley of different cultivars.

<p>The representatives are shown in blue with the closest species name and percentage identity of the 16S RNA gene in parentheses. Strains shown in gray were not pink-pigmented.</p

Isolates’ genotypes and characteristics of barley.

<p>Isolates’ genotypes and characteristics of barley.</p