Promoting successful healing of artificial trachea by intratracheal administration of basic fibroblast growth factor†.

OBJECTIVES: This study evaluated the effect of intratracheal administration of basic fibroblast growth factor (bFGF) on tracheal healing following implantation of a novel layered polyglycolic acid (PGA) material to replace a critical-size defect in rat trachea. METHODS: A critical-size defect in the rat cervical trachea was covered with PGA. Distilled water (DW) or 3.125, 6.25, 12.5 or 25 µg bFGF was administered into the trachea for 2 weeks (n = 6 for each of 5 groups). Regenerated areas of cilia, ciliary beat frequency and ciliary transport function (CTF) in the centre of the PGA were measured. To examine potential side effects of intratracheal administration of bFGF, the right lower lobe was pathologically evaluated. RESULTS: All rats survived during the study period. Histological examination showed ciliated epithelization on the PGA material after 2 weeks. Bronchoscopy revealed stenosis due to granulation following administration of high concentrations of bFGF (12.5 and 25 µg). Compared with the DW group, groups administered 3.125, 6.25, 12.5 and 25 µg bFGF had significantly larger areas of regenerated cilia (15.2%, 27.0%, 41.3%, 33.1% and 31.0%, respectively; P = 0.00143), improved ciliary beat frequency (7.10, 8.18, 10.10, 9.50 and 9.50 Hz, respectively), and improved CTS (6.40, 9.54, 16.89, 16.41 and 14.29 µm/sec, respectively). Pathological examination of the right lower lobe revealed pulmonary fibrosis and hyperplasia with high concentrations of bFGF (12.5 and 25 µg). CONCLUSIONS: Intratracheal administration of bFGF effectively promoted tracheal regeneration at an optimal dose of 6.25 µg following implantation of an artificial trachea.

Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169+ macrophages by metastatic breast cancers.

BACKGROUND: Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes. METHODS: We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients). FINDINGS: The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm2, p = 0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169+ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169+ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022). INTERPRETATION: We concluded that lymph nodes with breast cancer metastases have fewer CD169+ macrophages, which may be detrimental to the activity of anti-cancer immunity. FUNDING: JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS.

Investigation of predictors for in-hospital death or long-term hospitalization in community-acquired pneumonia with risk factors for aspiration.

Background: It is known that the mortality of pneumonia in patients with risk factors for aspiration is worse than that in those without these risk factors. However, it is still unknown which risk factors for aspiration predict prognosis. Therefore, we aimed to determine which risk factors for aspiration are associated with death or prolonged hospitalization. Methods: We prospectively followed patients with community-acquired pneumonia at a single hospital providing acute to chronic care in Japan until they died or were discharged. Patients at any risk of aspiration were included. The associations between pneumonia severity, individual risk factors for aspiration, and in-hospital death or prolonged hospitalization were investigated. Overall survival was estimated by the Kaplan - Meier method, and the factors associated with in-hospital death or prolonged hospitalization were investigated by multivariate analysis using factors selected by a stepwise method. Results: In total, 765 patients with pneumonia and risk factors for aspiration were recruited. One hundred and ten patients deceased, and 259 patients were hospitalized over 27 days. In-hospital death increased as the number of risk factors for aspiration increased. In the multivariate analysis, male, impaired consciousness, acidemia, elevated blood urea nitrogen, and bedridden status before the onset of pneumonia were associated with in-hospital death (odds ratio [OR]: 2.5, 2.5, 3.6, 3.1, and 2.6; 95% confidence interval [CI]: 1.6-4.1, 1.4-4.2, 1.6-8.0, 1.9-5.0, and 1.6-4.2 respectively). In the Cox regression analysis, these factors were also associated with in-hospital death. None of the vital signs at admission were associated. Tachycardia, elevated blood urea nitrogen, hyponatremia, and bedridden status were associated with hospitalization for >27 days (OR: 4.1, 2.3, 4.3, and 2.9; 95% CI: 1.3-12.9, 1.5-3.4, 2.0-9.4, and 2.0-4.0, respectively). Conclusions: Blood sampling findings and bedridden status are useful for predicting in-hospital mortality and long-term hospitalization in patients with pneumonia and any risk factor for aspiration.

Quantitative assessment of gadolinium deposition in dentate nuclei with MR fingerprinting.

RATIONALE AND OBJECTIVES: Gadolinium deposition in the dentate nucleus (DN) has been evaluated by T1-weighted imaging (T1WI) and T1 (R1) mapping, but not MR fingerprinting (MRF). This study investigated associations between T1 and T2 values of DN and gadolinium-based contrast agents (GBCAs) using 2-dimensional MRF. MATERIALS AND METHODS: This study included 101 patients. Region of interest analysis was performed for T1 and T2 values of DN on MRF (T1-MRF, T2-MRF) and T1-weighted images (T1WI ratio). T1 and T2 ratios compared to normal cerebellar white matter (T1-MRF ratio, T2-MRF ratio) were calculated. The type of previous GBCA was confirmed in 79 patients, and linear regressions were performed between T1, T2 values and number of GBCAs. RESULTS: Good correlations were observed between T1-MRF and T1WI ratio (ρ = -0.69, P < 0.001) and between T1-MRF ratio and T1WI ratio (ρ = -0.76, P < 0.001). Mild correlations were observed between T2-MRF and T1WI ratio (ρ = -0.32, P < 0.001) and between T2-MRF ratio and T1WI ratio (ρ = -0.44, P < 0.001). The number of linear-type GBCAs was associated with T1-MRF (ß = -0.62, P < 0.001) and T1-MRF ratio (ß = -0.54, P < 0.001) in univariate linear regression analyses, and with T1-MRF (ß = -0.61, P < 0.001) and T1-MRF ratio (ß = -0.53, P < 0.001) in multivariate analysis. The number of linear-type GBCAs was associated with T2-MRF (ß = -0.30, P < 0.001) and T2-MRF ratio (ß = -0.29, P < 0.001) in univariate analyses, and with T2-MRF (ß = -0.31, P < 0.001) and T2-MRF ratio (ß = -0.32, P < 0.001) in multivariate analyses. No associations were observed between number of macrocyclic GBCAs and T1-MRF (ratio) or T2-MRF (ratio). CONCLUSION: The number of linear-type GBCA administrations was associated with lower T1 and T2 values (ratios) in DN.

Impact of wearing a surgical facemask during exercise on dyspnea in patients with chronic pulmonary infections: A randomized crossover study.

BACKGROUND: Wearing facemasks in public is effective in preventing viral transmission. However, no study has evaluated the impact of wearing facemasks during exercise on dyspnea in patients with chronic pulmonary infections from multifaceted aspects, including sensory qualities and emotional responses. The aim of this study was to evaluate facemask-related dyspnea during exercise in this patient population. METHODS: We conducted a randomized crossover study involving adult patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) or bronchiectasis who participated in exercise sessions, both with (mask-on) and without (mask-off) surgical facemasks. The sensory and emotional dimensions of dyspnea during each exercise session were assessed using the Multidimensional Dyspnea Profile. Statistical analyses were performed to identify factors associated with worsening scores for each dimension. RESULTS: Thirty-four patients (mean age [standard deviation]: 71.6 [8.6] years) were included in the analysis. The median [interquartile range] total scores for the sensory and emotional dimensions of dyspnea were 3.5 [1, 9.5] (mask-off) vs. 10 [5.5, 23.8] (mask-on) (P < 0.001) and 0 [0, 5] (mask-off) vs. 3 [0.8, 10.3] (mask-on) (P = 0.115), respectively. "Air hunger" was the primary sensory descriptor of mask-related dyspnea. Vital capacity (VC) < 80% of the predicted value was a significant risk factor for worsening sensory dimension scores when wearing masks (odds ratio [95% confidence interval]: 5.5 [1.16-26.1], P = 0.038). CONCLUSIONS: The findings of this study indicate that patients with NTM-PD or bronchiectasis, particularly those with VC <80% of the predicted value, are likely to experience the sensory dimension of dyspnea during exercise while wearing surgical facemasks.