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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. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Polyglycolic acid (PGA) sheets are difficult to adapt to the central airway because of poor durability against high air pressure. Therefore, we developed a novel layered PGA material to cover the central airway and examined its morphologic traits and functional performance as a potential tracheal replacement. METHODS A critical-size defect in rat cervical tracheas was covered with the material. Morphologic changes were bronchoscopically and pathologically evaluated. Functional performance was evaluated by regenerated ciliary area, ciliary beat frequency and ciliary transport function determined by measuring the moving distance of microspheres dropped onto the trachea (µm/s). The evaluation time points were 2 weeks, 1 month, 2 months and 6 months after surgery (n  = 5, respectively). RESULTS Forty rats underwent implantation, and all survived. Histological examination confirmed ciliated epithelization on the luminal surface after 2 weeks. Neovascularization was observed after 1 month, tracheal glands after 2 months and chondrocyte regeneration after 6 months. Although the material was gradually replaced by self-organization, tracheomalacia was not bronchoscopically observed at any time point. The area of regenerated cilia significantly increased between 2 weeks and 1 month (12.0% vs 30.0%; P  = 0.0216). The median ciliary beat frequency significantly improved between 2 weeks and 6 months (7.12 vs 10.04 Hz; P  = 0.0122). The median ciliary transport function was significantly improved between 2 weeks and 2 months (5.16 vs 13.49 µm/s; P  = 0.0216). CONCLUSIONS The novel PGA material showed excellent biocompatibility and tracheal regeneration both morphologically and functionally 6 months after tracheal implantation. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES We developed a novel wireless localization technique after electromagnetic navigation bronchoscopy-guided radiofrequency identification marker placement for fluoroscopically invisible small lung lesions. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared 2 marking approaches with or without cone-beam computed tomography (CBCT). METHODS Consecutive patients from January 2021 to March 2022 in our institution were enrolled. Markers were placed central to the lesions either in a bronchoscopic suite under intravenous anaesthesia or a hybrid operation theatre with CBCT under general anaesthesia. The efficacy of the 2 marking methods was compared using an inverse probability of treatment weighting adjusted analysis. RESULTS Totally 80 markers were placed (45 under CBCT and 35 under fluoroscopy) for 74 patients with 80 lesions [mean size: 6.9 mm (interquartile range: 5.1–8.4) at a median depth from the pleura of 14.0 mm (interquartile range: 8.5–19.5)]. The median distance from marker to lesion was 9.1 mm, with a pleural depth of 15.5 mm. The tumour resection rate was 97.5% (78/80) with the median surgical margin of 10.0 mm (interquartile range: 8.0–11.0). Although the bronchoscopy time was longer using CBCT because of the need for 2.8 scans per lesion, the distance from the marker to the lesion was shorter for marking using CBCT than marking using fluoroscopy (adjusted difference: −4.56, 95% confidence interval: −6.51 to −2.61, P  < 0.001). CONCLUSIONS Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking provided a high tumour resection rate with sufficient surgical margins. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo‐resistant urothelial carcinoma (UC). Patients and Methods: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). Results: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68–1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non‐squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15–0.90; P = 0.023) compared to patients with PUC. Conclusions: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo‐resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC. [ABSTRACT FROM AUTHOR]

We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp3 hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH2-linked analogue of antitumor-active KRN7000 and its glucose congener. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post‐ESD bleeding and drug differences in patients taking DOACs.We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri‐cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post‐ESD bleeding.The incidence of post‐ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post‐ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post‐ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran.The administration of DOACs was shown to be a possible factor involved in post‐ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD. [ABSTRACT FROM AUTHOR]

High‐efficiency solution‐processed organic solar cells based on narrow‐bandgap π‐conjugated oligomers are demonstrated by Takuma Yasuda, Chihaya Adachi, and co‐workers in article number 1400879. Well‐organized donor/acceptor bulk‐heterojunction domains with pronounced mesoscopic phase segregation are spontaneously formed in a photoactive binary blend layer. A high power conversion efficiency of 5.9% is achieved for small‐molecule organic solar cells. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC).Materials and Methods: The clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. Best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed with regard to the history of NMIBC treatment and BCG usage using propensity score matching (PSM).Results: A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 10.0 months), the OS from the initiation of pembrolizumab for patients with a NMIBC history (13.3 months, HR [95% CI] 0.79 [0.62-1.02], P = 0.073), those with a NMIBC history and BCG (12.1 months, HR 0.87 [0.64-1.17], P = 0.356), or those with a NMIBC history but not BCG (14.5 months, HR 0.68 [0.45-1.12], P = 0.061) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 24.5% vs. 31.0%, P = 0.222) and disease control rate (DCR, 56.1% vs. 52.1%, P = 0.501) of the 155 patients with an NMIBC history did not differ from those of 155 matched patients without an NMIBC history. Among those with an NMIBC history, the prior use of BCG did not affect OS (with vs. without BCG, 12.1 vs. 14.5 months, HR 1.29 [0.80-2.09], P = 0.295), ORR (24.5% vs. 34.0%, P = 0.298) or DCR (57.1% vs. 56.0%, P = 0.908). The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P = 0.042), whereas DCR between the 2 groups did not differ significantly (55.8% vs. 54.4%, P = 0.855).Conclusions: Our risk-adjusted analyses revealed that a history of prior NMIBC treatment, including intravesical BCG therapy, did not affect the treatment outcomes of pembrolizumab in metastatic UC patients. [ABSTRACT FROM AUTHOR]

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., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp 3 hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH 2 -linked analogue of antitumor-active KRN7000 and its glucose congener.

C-Linked carbohydrate structure, in which the cleavable O-glycosidic linkage is replaced by a carbon unit, is a useful tool for functional analyses of glycoconjugates. We describe a synthetic method for α-CH 2 -linked disaccharide structures, such as Glc(1,6)-Glc, by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp 3 hybridized xanthate donor and a carefully designed acceptor.