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Background: The phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population., Methods: This retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method., Results: From June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; P = .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event., Conclusions: This multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America., Methods: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples., Results: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01)., Conclusions: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

This study investigated the immune response of broiler chickens with oral treatment of a Lactobacillus spp. pool (PL) associated with microencapsulated recombinant proteins flagellin (FliC) and the subunit B of cholera toxin (CTB). Immune responses were evaluated by measuring IgA from intestinal fluid, serum IgY, and immunostaining of CD8(+) T lymphocytes present in the cecum. The evaluations were performed on d 0, 7, 14, 21, and 28 posttreatment. A significant increase (P < 0.05) was observed in IgA levels in all immunized groups, especially 3 wk after immunization. Treatments 2 (recombinant CTB) and 3 (recombinant FliC+CTB) showed the highest concentrations. Similarly, serum concentrations IgY (μg/mL) increased along the experiment, and the means for treatments 2 and 3 showed significant differences (P < 0.05) compared with controls, reaching concentrations of 533 and 540 μg/mL, respectively. The number of CD8(+) T lymphocytes in all treatments greatly differed (P < 0.05) compared with the negative control at 21 d posttreatment. However, only treatment 2 (recombinant CTB), 4 (PL), and 5 (recombinant FliC+ recombinant CTB + PL) remained significantly (P < 0.05) different from the control at 28 d posttreatment. Thus, it is concluded that the microencapsulated recombinant proteins administered orally to broiler chickens are capable of stimulating humoral and cellular immune response, and the combinations of these antigens with Lactobacillus spp. can influence the population of CD8(+) T cells residing in the cecum.

The protection level against Salmonella Enteritidis was evaluated in chickens after in ovo treatment with different species of Lactobacillus spp. inoculated into the air cell or by immersion in broth culture. Two hundred forty embryonated eggs were distributed into 8 groups, corresponding to treatments with Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus salivarius, and control. On d 18 of incubation, 4 groups were inoculated with 0.1 mL of inoculum in the air cell and 4 groups were immersed for 3 min in culture of each treatment. Two days after hatching, 0.5 mL of Salmonella Enteritidis culture was inoculated by the intraesophageal route. On d 5 of life, the chicks were euthanized and the ceca were processed to obtain Salmonella Enteritidis counts. There was no decrease in Salmonella Enteritidis colonization of chick ceca, regardless of treatment or route of administration. Lactobacillus spp. samples used in the treatment showed no probiotic potential in chicks when inoculated in ovo, in relation to Salmonella Enteritidis inhibition in poultry ceca.

This study aimed to characterize the in vitro and in vivo adhesion and immunomodulatory effect of Lactobacillus strains isolated from chickens. Lactobacillus samples isolated from 65-wk-old birds were identified by PCR; their adhesion was evaluated in vitro via basement membrane-type cell matrix and in vivo through carboxyfluorescein succinimidyl amino ester staining inoculation in 1-d-old birds and duodenum, jejunum, ileum, and cecum collections at 1, 4, 12, and 24 h after inoculation. The 5 best adhesive samples at the in vitro test formed a pool for total IgA and IgG measurement in sera and intestinal fluid. The birds were divided into groups by inoculation scheme: group 1 was treated with a pool of Lactobacillus spp. at 2-d-old and challenged 1 d later with Salmonella Enteritidis and then treated again with a pool of Lactobacillus spp. at 4 d of age; group 2 was treated with a pool of Lactobacillus spp. at 2 and 4 d of age; group 3 was challenged with Salmonella Enteritidis at 3 d of age; and group 4 was a negative control. Collections were taken at 7, 14, 21, 28, and 35 d after the first inoculation. The results suggest that basement membrane matrix use represents an important technique for triage of samples for subsequent in vivo evaluation and that carboxyfluorescein succinimidyl amino ester staining is efficient for identifying this bacterial characteristic. The Lactobacillus-treated groups (1 and 2) presented the highest IgA concentrations at the end of the experiment (12,054.6 and 10,568.4 ng/mL, respectively). The group 2 IgG values in intestinal fluid exceeded those of the other 3 groups (P < 0.05), peaking at 6.419 ng/mL. In most serum collections, the Lactobacillus-treated groups (1 and 2) did not differ significantly in IgG concentrations (P > 0.05), whereas group 3 presented the highest concentration of this antibody. It is concluded that there was greater adhesion of strains in the cecum and an important correlation between in vitro and in vivo results. These results also suggest the immunomodulatory action of Lactobacillus spp. in the chicken.

Unattended four-channel sleep apnea recording has been shown to be an accurate tool in the diagnosis of moderate to severe obstructive sleep apnea. We selected 11 patients with severe obstructive sleep apnea who had an apnea-hypopnea index (AHI) determined by unattended sleep apnea recording. The mean AHI was 41 (SD, 17.5). We began nasal continuous positive airway pressure (NCPAP) at home empirically with 5 cm to 7.5 cm of pressure for several nights. We then adjusted the level of NCPAP after telephone interview with the patients and their significant others. The level of NCPAP was increased by 2.5-cm increments until the patients reported cessation of snoring and symptom improvement. The mean NCPAP was 8.0 cm (SD, 1.4). We repeated the overnight sleep apnea recording while on NCPAP in all patients at home to determine their response to therapy. All 11 patients had documented return of their AHI to normal (mean AHI, 2.4; SD, 1.6). Statistically significant improvement was noted in the number of obstructive apneas, hypopneas, total respiratory events, and the AHI. Follow-up data confirmed that patients had improvement in their symptoms and remained compliant with therapy (mean follow-up = 18 months; SD, 10.2). No serious complications were encountered when NCPAP was introduced in an unattended setting. We were able to diagnose and treat these patients in an entirely outpatient setting.

An enzyme-linked immunosorbent assay (ELISA) was examined for its usefulness in detecting mycobacterial antigens in sputum. A double-antibody sandwich procedure was set up by using a commercially available hyperimmune serum directed against Mycobacterium bovis, BCG. The ELISA was able to detect 10 ng of protein per ml of BCG sonic extract. The system also clearly distinguished Mycobacterium tuberculosis organisms from Mycobacterium avium and Mycobacterium kansasii organisms. A total of 68 unknown sputum specimens submitted to the clinical laboratories for examination for tuberculosis were tested by ELISA. Of the 20 specimens that were smear positive and culture positive, 12 (60%) were positive by ELISA; 6 of the 11 (55%) smear-positive culture-negative samples were positive by ELISA; 1 of 2 (50%) of the smear-negative culture-positive samples was positive by ELISA; and only 3 of 35 (9%) of the smear-negative culture-negative samples were positive by ELISA. This approach offers promise as an aid in the presumptive differentiation of nontuberculous mycobacteria from the M. tuberculosis complex.