Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC.

Background: Public health measures have imposed drastic reductions in cancer screening programs at the beginning of the COVID-19 pandemic, with an unknown impact on the diagnosis and staging of colorectal cancer (CRC). Methods: Newly diagnosed CRC cases at the Centre Hospitalier de l’Université de Montréal (CHUM) were divided into two groups according to the timeline: pre-pandemic (1 January 2018–12 March 2020), and pandemic (13 March 2020–30 June 2021) periods. Colonoscopy, surgery, and staging at diagnosis during the pandemic period were compared to the pre-pandemic period. Results: 254 CRC diagnoses were made during the pre-pandemic period in comparison to 125 during the pandemic period. Mean diagnosis rates were lower in the pandemic period (7.8 vs. 9.8 diagnoses/month, p = 0.048). Colonoscopy deadlines were less respected in the pandemic period (51.7% vs. 38.3%, p = 0.049). The rate of elective surgery did not differ (2.9 vs. 3.5 surgeries/month, p = 0.39) and mean delays were similar (58.6 vs. 60.4 days, p = 0.77). Stages at diagnosis did not differ (p = 0.17). Most of the delayed colonoscopies led to a stage 0 or I CRC (p = 0.2). Conclusion: In our center, the COVID-19 pandemic resulted in a decreased rate of CRC diagnosis and increased endoscopic delays without affecting the rate of advanced stage disease. Delays to surgery were quite similar once the CRC diagnosis was established.

Surgery is the only potential curative option of CRLM if resectable. The curative approach in patients over 70 years old is challenging mainly because of comorbidities and other geriatric syndromes. Herein, we report outcomes of older patients with resectable CRLM in our center. We retrospectively analyzed characteristics and outcomes of older patients with CRLM operated at “Centre Hospitalier de l’Université de Montréal” (CHUM) between 2010 and 2019. We identified 210 patients aged ≥70 years with a median age of 76 (range: 70–85). CRLM were synchronous in 56% of patients. Median disease-free survival (DFS) was 41.3 months. Median overall survival (OS) was 62.2 months and estimated 5-year survival rate was 51.5% similar to those of younger counterparts. Patients with metachronous CRLM had a trend to a higher OS compared to those with synchronous disease (67.2 vs. 58.7 months; p = 0.42). Factors associated with lower survival in the multivariate analysis were right-sided tumors and increased Charlson Comorbidity index (CCI). Survival outcomes of patients aged ≥70 years were comparable to those of younger patients and those reported in the literature. Age should not be a limiting factor in the curative management of older patients with resectable CRLM.

Fecal microbiome culturomics of a cancer patient treated with immune checkpoint inhibitors led to the identification of a Gram-negative, rod-shaped, obligate anaerobic, non-motile, non-spore-forming bacterium, designated strain kh20^T, which was phylogenetically assigned to the genus Alistipes. Strain kh20^T demonstrated a 98.61% 16S rRNA sequence similarity with A.shahii WAL 8301^T. The bacteria cells generated catalase but no oxidase. Iso-C_15:0 (26.6%), anteiso-C_15:0 (19.9%), and iso-C_17:0 (17.2%) were the major cellular fatty acids identified in its composition. The G+C content of its genome was 57.2%. Strain kh20^T showed significantly low values for DNA-DNA Hybridation (DDH ≤ 33.70%) and Average Nucleotide Identity (ANI ≤ 86.35%) compared with other Alistipes species. Based on these findings, we concluded that strain kh20^T represented a novel bacterium, and we proposed the name Alistipes montrealensis sp. nov. (CECT 30384 and CSUR Q6005).

Early initiation of antiretroviral therapy (ART) in perinatally HIV-infected children significantly limits the establishment of the viral reservoir. However, the long-term impact of this intervention remains unclear. We measured the frequency of inducible, translation-competent, and replication-competent proviruses in samples from 62 children who initiated ART early and remained virally suppressed for up to 9.9 years. Only a small fraction of HIV genomes produced HIV transcripts, viral proteins, or infectious virions. Accordingly, replication-competent virus was detected in only 11% of the participants. Despite the predominance of naive cells in pediatric blood, most proviruses were detected in memory CD4 ⁺ T cells, especially central memory cells. Longitudinal analysis revealed a biphasic decay in HIV DNA: an initial decline followed by long-term stability, which was associated with extensive expansions of infected T cell clones. In contrast, inducible proviruses declined continuously and became undetectable in most children after 5 years. Near full-length sequencing of 1,305 HIV genomes revealed a dramatic reduction in genetically intact proviruses, from pre-ART to after 7 years of ART. Together, these findings suggest that the intact viral reservoir rapidly decays in early-treated children, offering critical insights for pediatric HIV cure strategies.