Search

The usefulness of the derived neutrophil-to-lymphocyte ratio (dNLR) and its dynamics before/after durvalumab consolidation therapy to predict safety or efficacy remains unclear. We retrospectively reviewed patients with locally advanced non-small cell lung cancer treated with durvalumab consolidation therapy after chemoradiotherapy (D group) or chemoradiotherapy alone (non-D group) at multiple institutions. We investigated the association between dNLR, or its dynamics, and pneumonitis, checkpoint inhibitor-related pneumonitis (CIP), irAEs, and efficacy. Ninety-eight and fifty-six patients were enrolled in the D and non-D groups, respectively. The dNLR at baseline was significantly lower in patients who experienced irAEs or CIP than in those who did not. The low dNLR group, 28 days following durvalumab consolidation therapy (dNLR28 ≤ 3), demonstrated longer progression-free survival (PFS) and overall survival (OS) than the high dNLR group (dNLR28 > 3) (PFS, hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.88, p = 0.020; OS, HR 0.39, 95% CI 0.16-0.94, p = 0.037). Among patients with high dNLR at baseline (dNLR > 3), the dNLR28 ≤ 3 group showed longer PFS than the dNLR28 > 3 group (p = 0.010). The dNLR is a predictive factor for irAEs and CIP in patients receiving durvalumab consolidation therapy. The dNLR at 28 days after durvalumab consolidation therapy and its dynamics predict favorable outcomes., (© 2024. The Author(s).)

Multiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.

To adapt to changeable or unfamiliar environments, it is important that animals develop strategies for goal-directed behaviors that meet the new challenges. We used a sequential paired-association task with asymmetric reward schedule to investigate how prefrontal neurons integrate multiple already-acquired associations to predict reward. Two types of reward-related neurons were observed in the lateral prefrontal cortex: one type predicted reward independent of physical properties of visual stimuli and the other encoded the reward value specific to a category of stimuli defined by the task requirements. Neurons of the latter type were able to predict reward on the basis of stimuli that had not yet been associated with reward, provided that another stimulus from the same category was paired with reward. The results suggest that prefrontal neurons can represent reward information on the basis of category and propagate this information to category members that have not been linked directly with any experience of reward.

Two hundred anaerobic isolates from clinical specimens were examined for beta-lactamase production by Nitrocefin methodology. Altogether, 77 strains were beta-lactamase producers. Organisms belonging to Bacteroides melaninogenicus group, i.e., B. intermedius and B. bivius, were found to have a significant frequency of beta-lactamase production. Substrate profile and sensitivity to the beta-lactamase inhibitors, sulbactam, clavulanic acid, cloxacillin, and cefmetazole, a cephamycin derivative, were determined for these enzymes. All enzymes hydrolyzed cephalosporins more rapidly than penicillins. Cefmetazole was not hydrolyzed at all. Strains of B. fragilis, B. thetaiotaomicron, B. uniformis, B. ovatus and B. oralis produced beta-lactamases sensitive to all four inhibitors. Strains of B. intermedius, B. bivius and B. disiens produced enzymes of different nature which were inhibited only by cefmetazole. B. vulgatus enzyme was inhibited by three of the four inhibitors. These results suggest that the beta-lactamases of the genus Bacteroides may be classified by substrate profile and inhibitor pattern.

The antibacterial activity of cefminox (CMNX) against anaerobic bacteria was studied in vitro. The results are as follows: 1. CMNX exerted antibacterial activity against a wide range of anaerobes, excluding Clostridium innocuum. The antibacterial activity of CMNX against Bacteroides fragilis was comparable to that of latamoxef and superior to cefoxitin, but CMNX's activity against anaerobic cocci was slightly inferior to cefoxitin's; 2. A comparison of the MICs and MBCs of CMNX indicated that this drug exerts a complete bactericidal effect at a concentration which inhibits the growth of bacteria; 3. CMNX was found to be stable to the beta-lactamases produced by B. fragilis; 4. CMNX exerted an antibacterial activity against C. difficile.