Search

This study evaluated the safety and effectiveness of dulaglutide in patients with type 2 diabetes in the real-world setting in Japan.This prospective, observational post-marketing surveillance study was conducted for 36 months (July 2016 to July 2021) in Japan. Investigators reported data via an electronic data capture system. Data were analyzed by overall population and age group (65, ≥65 to 75, and ≥75 years).The analysis population (N = 3,136) included 1,538 (49.04%), 869 (27.71%), and 729 (23.25%) patients aged65 years, ≥65 to75 years, and ≥75 years, respectively. Overall, 231 patients (7.37%) experienced ≥1 adverse drug reactions, with the highest frequency in the ≥75 years group. The most common adverse drug reactions were gastrointestinal disorders (n = 106; 3.38%). Severe hypoglycemia (n = 4; 0.13%), major adverse cardiovascular events (n = 4; 0.13%), and acute pancreatitis (n = 1; 0.03%) were uncommon. The mean glycated hemoglobin and bodyweight were reduced from baseline by -0.76% and -1.6 kg, respectively (last observation carried forward). The rate of dulaglutide continuation at 36 months was 58.03% overall and 59.43%, 63.13%, and 48.88% in the65, ≥65 to75, and ≥75 years groups, respectively. A factor analysis showed age ≥65 years was associated with a greater incidence of gastrointestinal adverse drug reactions as well as larger reductions in glycated hemoglobin and bodyweight.The current real-world data are in accordance with clinical trial findings and further confirm the safety and effectiveness of dulaglutide for elderly patients, whose numbers were limited in the clinical trials.

Background Granulosa cell tumors (GCTs) are uncommon sex cord-stromal ovarian neoplasms. We report a case of GCT presenting in the chest, 18 years after oophorectomy for ovarian cystadenocarcinoma. Case presentation A 63-year-old female was admitted to our hospital for evaluation of a right hilar lesion. Subsequent abdominal and pelvic computed tomography and brain magnetic resonance imaging were unremarkable. Eighteen years earlier, the patient had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy at another institution for a uterine myoma, with the pathological findings indicating a uterine myoma, dermoid cyst of the right ovary, and serous cystadenocarcinoma and endometrioid adenoacanthofibroma around hemorrhagic cyst of the left ovary. No indication of a granulosa cell tumor (GCT) was present in either ovary. As such, diagnostic video-assisted thoracoscopic surgery was performed, revealing a well encapsulated tumor located next to the inferior pulmonary vein and small, disseminated lesions on the chest wall and diaphragm. Thereafter, we performed resection of the main tumor in its entirety and the disseminated lesions to the extent possible. Pathological examination of the resected specimens revealed a neoplasm characterized by sheets and islands of closely packed tumor cells exhibiting small follicles (Call-Exner bodies) surrounded by cells with pale, uniform nuclei, typically observed in the microfollicular pattern of adult GCT. Although the etiology of occurrence of intrathoracic granulosa cell tumor is unknown, we assumed that the neoplasm oriented from radiologically undetectable peritoneal seeding at the time of her previous surgery, with subsequent migration through the diaphragm. Over the next 10 years, she received chemotherapy with cyclophosphamide, adriamycin, and cisplatin; other combination chemotherapy; single-agent chemotherapy; and palliative radiotherapy. She died from malignant pleuritis and peritonitis 10 years after thoracoscopic surgery. Conclusions We have reported a case of a 63-year-old female with a history of ovarian cystadenocarcinoma who underwent resection of a pleural neoplasm, which turned out to be a granulosa cell tumor. This possibility resulted from dissemination of a previous abdominal lesion.

A series of poly(phenylene sulfide) (PPS) derivatives can be bleached while maintaining high refractive indices, by partially incorporating sulfoxide bonds through their mCPBA oxidation, owing to the loss of lone pairs around the sulfide atoms.

Senescent cells exhibit several typical features, including the senescence-associated secretory phenotype (SASP), promoting the secretion of various inflammatory proteins and small extracellular vesicles (EVs). SASP factors cause chronic inflammation, leading to age-related diseases. Recently, therapeutic strategies targeting senescent cells, known as senolytics, have gained attention; however, noninvasive methods to detect senescent cells in living organisms have not been established. Therefore, the goal of this study was to identify novel senescent markers using small EVs (sEVs). sEVs were isolated from young and senescent fibroblasts using three different methods, including size-exclusion chromatography, affinity column for phosphatidylserine, and immunoprecipitation using antibodies against tetraspanin proteins, followed by mass spectrometry. Principal component analysis revealed that the protein composition of sEVs released from senescent cells was significantly different from that of young cells. Importantly, we identified ATP6V0D1 and RTN4 as novel markers that are frequently upregulated in sEVs from senescent and progeria cells derived from patients with Werner syndrome. Furthermore, these two proteins were significantly enriched in sEVs from the serum of aged mice. This study supports the potential use of senescent markers from sEVs to detect the presence of senescent cells in vivo.

Background A combination of chlorhexidine gluconate and alcohol (CHG–alcohol) is recommended for surgical skin preparation to prevent surgical site infection (SSI). Although more than 1 per cent CHG–alcohol is recommended to prevent catheter-related bloodstream infections, there is no consensus regarding the concentration of the CHG compound for the prevention of SSI. Methods A systematic review and meta-analysis was performed. Four electronic databases were searched on 5 November 2020. SSI rates were compared between CHG–alcohol and povidone-iodine (PVP-I) according to the concentration of CHG (0.5 per cent, 2.0 per cent, 2.5 per cent, and 4.0 per cent). Results In total, 106 of 2716 screened articles were retrieved for full-text review. The risk ratios (RRs) of SSI for 0.5 per cent (6 studies) and 2.0 per cent (4 studies) CHG–alcohol were significantly lower than those for PVP-I (RR = 0.71, 95 per cent confidence interval (c.i.) 0.52 to 0.97; RR = 0.52, 95 per cent c.i 0.31 to 0.86 respectively); however, no significant difference was observed in the compounds with a CHG concentration of more than 2.0 per cent. Conclusions This meta-analysis is the first study that clarifies the usefulness of an alcohol-based CHG solution with a 0.5 per cent or higher CHG concentration for surgical skin preparation to prevent SSI.

International audience; PFS (Prime Focus Spectrograph), a next generation facility instrument on the Subaru telescope, is now being tested on the telescope. The instrument is equipped with very wide (1.3 degrees in diameter) field of view on the Subaru's prime focus, high multiplexity by 2394 reconfigurable fibers, and wide waveband spectrograph that covers from 380nm to 1260nm simultaneously in one exposure. Currently engineering observations are ongoing with Prime Focus Instrument (PFI), Metrology Camera System (MCS), the first spectrpgraph module (SM1) with visible cameras and the first fiber cable providing optical link between PFI and SM1. Among the rest of the hardware, the second fiber cable has been already installed on the telescope and in the dome building since April 2022, and the two others were also delivered in June 2022. The integration and test of next SMs including near-infrared cameras are ongoing for timely deliveries. The progress in the software development is also worth noting. The instrument control software delivered with the subsystems is being well integrated with its system-level layer, the telescope system, observation planning software and associated databases. The data reduction pipelines are also rapidly progressing especially since sky spectra started being taken in early 2021 using Subaru Nigh Sky Spectrograph (SuNSS), and more recently using PFI during the engineering observations. In parallel to these instrumentation activities, the PFS science team in the collaboration is timely formulating a plan of large-sky survey observation to be proposed and conducted as a Subaru Strategic Program (SSP) from 2024. In this article, we report these recent progresses, ongoing developments and future perspectives of the PFS instrumentation.

Background: A consensus on preferred treatment for patients with EGFR-mutated (EGFRm) advanced or metastatic non-small-cell lung cancer (a/mNSCLC) who have progressed on osimertinib and platinum-based chemotherapy (PBC) has yet to be established. The study objectives were to describe patient characteristics and treatment patterns in this context and assess corresponding clinical outcomes in the US real-world setting. Methods: This study was a retrospective analysis of data sourced from Flatiron’s de-identified database, which included electronic health records and curated cancer data from approximately 280 US cancer clinics (~800 US sites of care). The index line of therapy (LOT) was defined as initiation of a new treatment regimen after osimertinib and PBC. Adults were eligible for inclusion if they: 1) were diagnosed with a/mNSCLC on or after January 1, 2011; 2) had evidence of an activating EGFR mutation (exon 19 or L858R); 3) initiated a new LOT between November 13, 2015, and June 30, 2021, after treatment with osimertinib and PBC. Treatment regimens in the index LOT were summarized, and real-world overall survival (rwOS, defined as the time from initiation of index LOT to death) and real-world progression-free survival (rwPFS, defined as the time from initiation of index LOT to disease progression or death) were assessed. Results: Among 273 study patients included, the majority were ≥65 years (57%), female (67%), Caucasian (65%; Asian, 17%; Black or African American, 6%), with no history of smoking (58%), performance status 0-1 (82%), and >2 prior LOT (64%). Median follow-up duration was 7.3 months. Index treatment regimens were classified as tyrosine kinase inhibitor (TKI) monotherapy (15%) or TKI in combination with non-immuno-oncologic agents (12%), non-platinum-based chemotherapy (23%), immuno-oncologic monotherapy (17%) or combination therapy (15%), PBC (12%), a regimen containing a clinical study drug (4%), or other NSCLC therapy (1%). Deaths occurred in 203 patients (74%) during follow-up; median rwOS was 8.6 months (95% confidence interval [CI], 7.4-9.8). Real-world progression occurred in 235 patients (86%); median rwPFS was 3.3 months (95% CI, 2.8-4.4). Conclusions: For patients with EGFRm a/mNSCLC, third-generation EGFR TKIs such as osimertinib can provide disease control, however progression is common. After disease progression, chemotherapy is often the next treatment of choice. Results of this real-world study show that treatment patterns after EGFR TKI and PBC are highly variable and suggest poor clinical outcomes, highlighting the need for more efficacious treatments among patients with previously treated a/mNSCLC. Citation Format: Jyoti D. Patel, Jie Meng, Sudarshan Phani, Aaron Crowley, Summera Zhou, Maribel Salas, Yoko Tanaka, Hoa Le, Jeffrey Anderson, Karen L. Reckamp. Clinical characteristics, real-world treatment patterns, and clinical outcomes among patients with previously treated metastatic or unresectable EGFR-mutated non-small cell lung cancer in the United States. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6754.

We aimed to investigate if Computed tomography (CT) attenuation values can help improve the identification of age-related changes in the thymus. We assessed CT images of 405 patients aged 0 to 80 years. We measured the area of the anterior mediastinum at the level of the carina and its average CT attenuation value. We evaluated the thymic area, the ratio of the thymus area to the total thoracic area, and the CT attenuation value. Additionally, we evaluated changes in the thymus area in the 0 to 13-year age group. The area of the thymus decreased from birth to the middle 20s. After the middle 20s, the area tended to increase and plateau till after 50 years of age. The ratio of the thymic area to the thoracic area decreased from age 0 to 20 years, but remained stable after 20 years of age. The CT attenuation values were stable from birth to puberty, decreased after puberty, and were stable again in the late 50s and beyond. The thymus of children showed mass formation, but the shape changed with age. No significant differences in the CT attenuation value were found across underlying conditions for the 0 to 13-year age group. The decrease in the CT attenuation values, observed with advancing age, reflects adipose degeneration of the thymus, indicating that by the late 50s, thymic tissue is replaced completely by adipose tissue. Our data suggest that adipose degeneration of the thymus begins after puberty and advances with age.