T-Bactum (EB23 18235Y / EB2318235Y)

Acute effects of oxygen supplementation on quadriceps Neuromuscular Fatigue in COPD patients with Chronic Respiratory Failure.

Paneroni Mara M, Vitacca Michele M, Simonelli Carla C, Spinello Laura L et al.

Patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure (CRF) under Long Term Oxygen Therapy (LTOT) experience exaggerated quadriceps neuromuscular fatigue (NMF). In this context, the effect of oxygen therapy on NMF remains unclear. What is the impact of different FiO2 levels on neuromuscular fatigue during intermittent isometric quadriceps exercise in a COPD-CRF population? Three intermittent isometric quadriceps tests (Ts), all at 80% of the time to exhaustion (TTE) at 30% of Maximal Voluntary Contraction (MVC), were randomly performed in each patient under three different FiO2 (F): T-F21 at 21%, T-F30 at30%, T-F60 at 60%. TTE was previously evaluated by breathing FiO2 at 21%. NMF was assessed through changes in MVC, twitch force quadriceps potentiated (Qtwpot), and voluntary activation (VA), following exercise (at peak, and at 30" and 10' after). EMG was continuously evaluated. We enrolled 20 patients (80.9% male, 71.80±5.81 years, FEV1/FVC 39.56±9.32, RV 206.49±53.14%). MVC changes were -27.60±9.50%, -24.35±7.80%, and -22.00±7.13% in T-F21, T-F30, and T-F60, respectively (P = 0.0341), with differences between T-F21 and T-F30 (P = 0.032) and T-F21 and T-F60 (P = 0.032). ΔQtwpot showed changes of -31.10±14.30%, -31.25±16.70%, and -26.70±16.10% for T-F21, T-F30, and T-F60, respectively (P = 0.019), with differences between T-F21 and T-F60 (P = 0.027) and T-F30 and T-F60 (P = 0.014). VA decreased similarly across conditions (P=0.211). Acute oxygen administration reduces quadriceps NMF in COPD patients with CRF. These results highlight the role of oxygen availability in modulating NMF in this population. Future studies should investigate this effect during exercise training, as well as long-term consequences.

Integrated analysis of scRNA-seq and TCR-seq on T cells in aneurysmal subarachnoid hemorrhage: A descriptive, hypothesis-generating case study.

Meng Ningqin N, Li Xingrao X, Ye Ziming Z, Xie Xufeng X et al.

This studthe transcriptomic profiles and T cell receptor (TCR) repertoires of T cells in paired cerebrospinal fluid (CSF) and peripheral blood (PB) from 2 patients with aneurysmal subarachnoid hemorrhage (SAH). This descriptive work primarily generates research hypotheses and does not explore causal biological mechanisms. Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) were performed on T cells isolated from CSF and PB samples collected on day 7 post-onset from 2 male patients. A series of descriptive analyses were conducted, including T cell subset classification, pseudotime trajectory reconstruction, pathway enrichment, CellChat-based cell-cell communication analysis, and TCR clonality assessment. Public scRNA-seq data of CSF samples from 8 healthy individuals were downloaded from the Gene Expression Omnibus database and used as external healthy controls. A total of 6058 T cells for scRNA-seq and 5008 T cells for TCR-seq were analyzed in this study. Five distinct T cell subsets were observed. In these 2 patients, CSF-derived T cells showed stronger signaling pathway activation and increased clonal expansion than PB-derived T cells. Compared with healthy controls from the public dataset, T cells from SAH patients presented enhanced signaling pathway activity and more extensive cell-cell interactions. All above observations are limited to these 2 individuals and cannot be generalized to all SAH patients without large independent cohort validation. This descriptive case-based study establishes a high-resolution single-cell atlas of T cells from 2 SAH patients. The observed differences between CSF and PB, as well as between SAH patients and healthy controls, provide directions for future mechanistic investigations.

Fate of hepatitis D virus-specific CD8+ T cells during bulevirtide monotherapy in patients with chronic hepatitis delta☆.

Oberhardt Valerie V, Degasperi Elisabetta E, Maas Michelle M, Borghi Marta M et al.

Bulevirtide reduces viremia in chronic hepatitis D virus (HDV) infection, but long-term treatment is required in most patients to prevent relapse. Sustained treatment responses may be fostered by therapy-induced amelioration of HDV-specific CD8+ T-cell responses that are exhausted due to high viremia and antigen loads during chronic HDV infection. We therefore studied the effect of bulevirtide monotherapy on HDV-specific CD8+ T-cell repertoire, phenotype, and functionality. 28 HDV-infected cirrhotic patients starting bulevirtide treatment were followed for 40-120 weeks on treatment. HLA-class-I typing and HDV sequencing was performed. HDV-specific CD8+ T cells were analyzed longitudinally using optimal epitopes and overlapping peptides spanning the L-HDAg. Ex vivo high-dimensional flow cytometry analysis of peptide/HLA class I tetramer+ CD8+ T cells was performed longitudinally in selected patients. In 42% of patients, an HDV-specific CD8+ T-cell response was detectable at baseline, but did not substantially increase during treatment. Importantly, a large majority of HDV-specific CD8+ T-cell responses targeted viral epitopes with sequence variations consistent with viral escape mutations. Only one HLA-B*35-restricted HDV-specific CD8+ T-cell epitope was conserved and continuously targeted throughout therapy. HDV-specific CD8+ T cells targeting this conserved epitope displayed a predominant terminally exhausted phenotype at baseline that shifted longitudinally to a memory-like phenotype with suppression of HDV load. Albeit based on small patient numbers, antiviral treatment with bulevirtide could ameliorate exhausted HDV-specific CD8+ T cells targeting conserved HDV epitopes. However, as the majority of HDV-specific CD8+ T-cell responses target escaped viral epitopes, this does not translate to a substantial improvement in overall HDV-specific CD8+ T-cell immunity. Our findings may explain in part why long-term bulevirtide treatment is required to prevent viral relapse.

Early Acute Leukemia Relapse After CD19-Directed CAR-T With Lineage Switch From B to T-ALL in a Pediatric Patient.

Wang Yannan J YJ, Beri Nefeli N, Sirotnikov Sam S, Kirsch Ilan I et al.