BACKGROUND: Preclinical studies suggest that combining nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, with pomalidomide/dexamethasone (Pd) with or without elotuzumab, an antisignaling lymphocytic activation molecule F7 monoclonal antibody, may improve multiple myeloma (MM) treatment efficacy. PATIENTS AND METHODS: The phase 3 CheckMate 602 study (NCT02726581) assessed the efficacy and safety of nivolumab plus pomalidomide/dexamethasone (NPd) and NPd plus elotuzumab (NE-Pd). Eligible patients (aged ≥ 18 years) had measurable MM after ≥ 2 prior lines of therapy, that included an immunomodulatory drug (IMiD) and proteasome inhibitor (PI), each for ≥ 2 consecutive cycles, alone or combined, and were refractory to their last line of therapy. Patients were randomized 3:3:1 to receive NPd, Pd, or NE-Pd. The primary endpoint was progression-free survival (PFS); overall response rate (ORR) was a key secondary endpoint. RESULTS: At a median follow-up of 16.8 months, PFS was similar between treatment arms (Pd, 7.3 months [95% CI, 6.5-8.4]; NPd, 8.4 months [95% CI, 5.8-12.1]; NE-Pd, 6.3 months [95% CI, 2.4-11.1]). ORR was similar in the Pd (55%), NPd (48%), and NE-Pd (42%) arms. Nivolumab-containing arms were associated with a less favorable safety profile versus Pd, including a higher rate of thrombocytopenia (NPd, 25.0%; NE-Pd, 16.7%; Pd, 15.7%), any-grade immune-mediated adverse events (NPd, 13.9%; NE-Pd, 16.7%; Pd, 2.9%), and adverse events leading to discontinuation (NPd, 25.0%; NE-Pd, 33.3%; Pd, 18.6%). No new safety signals were identified. CONCLUSION: CheckMate 602 did not demonstrate clinical benefit of nivolumab (+/- elotuzumab) plus Pd versus Pd for patients with relapsed/refractory MM (RRMM).

• MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• nivolumab * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   farmakologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thalidomid * analogy a deriváty   terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986-0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.

• MeSH
• deep learning * MeSH
• duktální karcinom slinivky břišní * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• nádory slinivky břišní * diagnostické zobrazování   patologie   MeSH
• pankreas diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• retrospektivní studie MeSH
• umělá inteligence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Abscesses are often clinically manifested as local necrotic tissues in various organs or systems of the human body, which is commonly caused by microbial infection. Rapid and accurate identification of pathogens from clinical abscetic samples would greatly guide a clinician to make the precise choices of the antimicrobial treatment. Here, this study aimed to investigate the application of metagenomic next-generation sequencing (mNGS) in the microbial detection of clinical samples of abscess fluids from various organs or systems. Nine patients with abscess from various organs or systems were enrolled in this study. The pathogenic bacteria in abscess fluid were detected and compared by the conventional bacterial culture and mNGS respectively. The dominant pathogens of abscess fluids in 8 cases can be found directly from mNGS, dominating over 80% of the total reads abundance of the microbiome. Although the pathogens from 6 cases detected by mNGS were consistent with that from the conventional bacteria culture method, the fastidious obligate anaerobic bacteria in 2 cases additionally detected by mNGS were not found by the conventional culture method. Moreover, complex polymicrobial infection containing Parvimonas micra in one case negatively with conventional bacterial culture were demonstrated by the mNGS method. And the mNGS method can directly reflect the diversity of microbial ecology in the abscess fluids from the different parts of the human body. Conclusively, mNGS can be used as a supplemental method for the pathogen detection of clinically abscess fluids.

• MeSH
• absces * diagnóza   MeSH
• Firmicutes MeSH
• lidé MeSH
• metagenomika * MeSH
• senzitivita a specificita MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• autofagie * fyziologie   MeSH
• autofagozomy MeSH
• biologické markery MeSH
• biotest normy   MeSH
• lidé MeSH
• lyzozomy MeSH
• proteiny spojené s autofagií metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• směrnice MeSH

• MeSH
• autofagie * fyziologie   MeSH
• biotest metody   normy   MeSH
• lidé MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice MeSH

AIM: To determine the anti-edema effects of melatonin on spinal cord injury (SCI) in rats. METHODS: A total of 150 adult male Sprague-Dawley rats were randomly allocated to the following three groups (n=50): a sham group which underwent laminectomy without dural compression; an SCI group, which underwent laminectomy followed by SCI and received saline i.p. immediately after injury and then daily for 2 days; an MT group, which underwent laminectomy followed by SCI and received a 100 mg/kg dose of melatonin i.p. immediately after SCI and then daily for 2 days. The cords were removed at 12, 24, 48 and 72 h after surgery in every group. Spinal cord edema was evaluated by determining the spinal cord water content. Expressions of AQP4 and GFAP positive cells in injured spinal cord were detected by immunohistochemical staining, and protein expressions of AQP4 and GFAP were detected by Western blotting. RESULTS: Spinal cord water content was obviously increased after SCI, which was maintained almost unchanged by melatonin treatment (100 mg/kg) at 12 h after injury but was significantly reduced from 24 h to 72 h. The expressions of AQP4 and GFAP increased in the injured spinal cord segments, which were decreased by melatonin treatment (100 mg/kg) between 24 h and 72 h after SCI. CONCLUSIONS: Melatonin (100 mg/kg) had anti-edema effects after acute SCI probably by down-regulating the expression level of AQP4 protein, and it may eliminate astrocytic swelling after SCI through down-regulating the expression level of GFAP protein.

• MeSH
• akvaporin 4 metabolismus   MeSH
• antioxidancia aplikace a dávkování   farmakologie   MeSH
• down regulace MeSH
• edém prevence a kontrola   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• laminektomie MeSH
• melatonin aplikace a dávkování   farmakologie   MeSH
• mícha chemie   metabolismus   MeSH
• náhodné rozdělení MeSH
• poranění míchy komplikace   MeSH
• potkani Sprague-Dawley MeSH
• tělesná voda metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH