Wild mushroom poisoning is a global public health concern, with mushrooms containing amatoxins being the main cause of fatalities. Mushrooms from the genus Amanita and Galerina contain amatoxins. Here we present a case of wild mushroom poisoning that affected three individuals, resulting in two fatalities. Within 10–15 hours after consumption, they experienced symptoms of gastroenteritis such as vomiting, abdominal pain, and diarrhea. One individual sought medical attention promptly and recovered, while the other two sought medical help nearly two or three days after the onset of symptoms, by which time their conditions had already worsened and led to their deaths. The mushrooms were identified belonging to genus Galerina, and laboratory test revealed variations in toxin levels among mushrooms collected from different parts of the decaying stump. The higher levels of α-amanitin, β-amanitin, and γ-amanitin were detected near the base of the tree stump, but trace levels of α-amanitin were found near the top of the stump, while β-amanitin and γ-amanitin were undetectable. This case emphasizes the importance of seeking immediate medical attention when experiencing delayed-onset gastrointestinal symptoms, as it may indicate more severe mushroom poisoning, particularly amatoxin poisoning. Timely and appropriate treatment is equally important. Additionally, consuming different units of the mushrooms in the same incident can lead to varying prognoses due to differences in toxin levels.
Abstract Background POLARIS is an ongoing, prospective, real-world (RW) study of palbociclib (PAL) in patients (pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). A biomarker goal of this study was to evaluate serial changes in circulating tumor DNA (ctDNA) dynamics among pts with long-term clinical response to PAL plus endocrine therapy (ie, received ≥18 cycles). Methods The data set included pts who received PAL combination therapy, gave consent for blood collection to obtain ctDNA, and had long-term clinical response. The Guardant360 Next-Generation Sequencing platform, which analyzed approximately 73 genes, was used to sequence ctDNA for somatic single-nucleotide variants, including copy number variants. Longitudinal ctDNA changes (at baseline and various time points) and the RW clinical response to PAL are described. Results As of December 17, 2020, 35 pts of 1280 enrolled received ≥18 cycles of PAL combination therapy, with blood samples collected over a minimum of a 24-month period. Pts received PAL plus an aromatase inhibitor (n=16) or fulvestrant (n=19). Median age was 64 years. Thirty pts (85.7%) were white, 29 (82.9%) were postmenopausal, 31 (88.6%) had an Eastern Cooperative Oncology Group score of 0 or 1, 12 (34.3%) had visceral disease, 9 (25.7%) had de novo disease, and 24 (68.6%) had recurrent disease. Six pts (17.1%) had a RW best overall response (BOR) of complete response (CR), 9 (25.7%) had partial response (PR), and 20 (57.1%) had stable disease (SD). Two pts had disease progression resulting in change of therapy at cycles 25 and 38, respectively. Biomarker samples were collected from a median (range) total number of 9 (3-12) visits. The median (range) number of somatic variants detected was 4 (0-11) and included the most prevalent somatic mutations (eg, PIK3CA, TP53, BRCA1/2, FGFR2, GATA3). No ctDNA mutations were detected in 6 pts (17%) post baseline up to 24 months. Among 15 pts who achieved CR/PR, 12 (80%) either had no detectable or sustained very low ctDNA burden or had corresponding ctDNA decrease. Among 16 pts who remained with SD, 12 (75%) either had no detectable or sustained very low ctDNA burden or had ctDNA decrease. Among 8 pts whose disease progressed, 5 (63%) had an increasing trend in ctDNA mutation frequency. Conclusions This study is among the first to provide serial blood-based tumor genotyping data from routine clinical practice. Interim data indicate that even pts with ongoing detectable ctDNA have a BOR of CR, PR, or SD with PAL for HR+/HER2- ABC, suggesting certain mutations might not be drivers of PAL resistance. Dynamic changes of ctDNA mutations may be predictive for treatment response, and may have clinical utility in disease surveillance monitoring. Additional longitudinal data will be presented. Pfizer; NCT03280303 Citation Format: Joanne L. Blum, Aditya Bardia, Sharon Wilks, Steven L. McCune, Carrie L. Dul, John J. Migas, Derrick W. Spell, Zhe Zhang, Yuan Liu, Yao Wang, Debu Tripathy. Longitudinal ctDNA changes in patients with long-term response to palbociclib combination therapy for advanced breast cancer: A preliminary analysis from the real-world POLARIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB033.
Abstract Background: POLARIS is an ongoing, prospective, real world, noninterventional study in patients (pts) with HR+/HER2– ABC receiving PAL. This interim report describes real-world PAL use in preMeno pts. Methods: POLARIS has a targeted enrollment of 1500 pts from ~110 sites in the United States and Canada. Using patient data collected from medical charts and physician surveys, baseline demographics, clinical characteristics, and treatment patterns were analyzed descriptively in self-reported preMeno pts with ABC. Results: At the data cutoff of May 20, 2020, 1208 pts were enrolled; 134 (11.1%) from 61 sites were preMeno, of whom 14.2% completed ≥6 months of PAL treatment. Among 134 preMeno pts (74.6%) who received first-line (1L) therapy, 69.0% received PAL+letrozole (LET) or anastrozole, 28.0% PAL+fulvestrant, and 3.0% PAL+exemestane. Median disease-free interval was 39.3 (range: 0 to 236) months; median treatment-free interval was 14.8 (-3 to 134) months. Of 34 pts (25.4%) who received PAL as second or later line (≥2L), 23.8% previously received hormonal therapy, 28.6% chemotherapy, and 14.3% both. The majority of pts (96.27%) initiated PAL at 125 mg regardless of line of therapy (Table). During the first PAL treatment cycle, 2.9% of all preMeno pts, 1% of 1L pts, and 8.8% of ≥2L pts had a dose reduction; 8.2%, 9%, and 5.9%, respectively, had an interruption. Dose reductions/interruptions peaked in cycle 2 (11.9%/15.7%); 56.67% of these modifications were due to adverse events. Conclusions: PAL is routinely prescribed in clinical practice for preMeno women with HR+/HER2- ABC. The majority of preMeno pts in this real-world dataset received PAL+LET as 1L ABC treatment; PAL was primarily initiated at the recommended dose (125 mg) and was well tolerated with few dose modifications required. Clinical trial identification: Pfizer (NCT03280303) Table.CharacteristicFirst-Line Pre/Perimenopausal Patients (n=100)Second or Later Line Pre/Perimenopausal Patients (n=34)Pre/Perimenopausal Patients (N=134)Age at study enrollment, yMedian (range)44 (22-61)42.5 (27-58)44 (22-61)Distribution, n (%)<4032 (32.0)12 (35.3)44 (32.8)40–5045 (45.0)17 (50.0)62 (46.3)51–6923 (23.0)5 (14.7)28 (20.9)Race, n (%)White73 (73.0)26 (76.5)99 (73.9)Black or African American16 (16.0)4 (11.8)20 (14.9)Asian1 (1.0)1 (2.9)2 (1.5)Native Hawaiian or other Pacific Islander2 (2.0)0 (0.0)2 (1.5)American Indian or Alaska Native1 (1.0)0 (0.0)1 (0.7)Other3 (3.0)2 (5.9)5 (3.7)Not reported because of confidentiality regulations4 (4.0)1 (2.9)5 (3.7)Hispanic/Latino ethnicity, n (%)10 (10.0)3 (8.8)13 (9.7)Disease status, n (%)Visceral35 (35.0)13 (38.2)48 (35.8)Nonvisceral61 (61.0)17 (50.0)78 (58.2)Not reported4 (4.0)4 (11.8)8 (6.0)Bone metastases at mBC diagnosis, among patients with metastatic (stage IV) disease at study enrollment, n (%)Bone only40 (40)8 (23.5)48 (35.8)Bone plus other metastases32 (32)13 (38.2)45 (33.6)Disposition of patient ABC/mBC diagnosis at study at study enrollment, n (%)Recurrent from earlier stage (Stage 0-III)72 (72.0)18 (52.9)90 (67.2)De novo (Newly diagnosed Stage IV at enrollment)26 (26.0)15 (44.1)41 (30.6)Not reported2 (2.0)1 (2.9)3 (2.2)ECOG performance status at study enrollment (N, %)041 (41)15 (44.1)56 (41.8)126 (26)7 (20.6)33 (24.6)28 (8)3 (8.8)11 (8.2)32 (2)0 (0)2 (1.5)Not reported23 (23)9 (26.5)32 (23.9)Starting dose, first cycle of PAL treatment n (%)125 mg96 (96.0)33 (97.1)129 (96.3)100 mg2 (2.0)1 (2.9)3 (2.2)75 mg2 (2.0)0 (0.0)2 (1.5)Reason for first cycle starting dose <125 mg, n (%)Patient preference0 (0.0)1 (100)1 (25.0)Other3 (100)0 (0.0)3 (75.0) Citation Format: Meghan S Karuturi, Adnan Garrett, Joanne L Blum, Jay Anderson, Erin Jepsen, Timothy Pluard, Thomas Stanton, Kenneth Manning, Joseph C Cappelleri, Faith Beery, Yao Wang, Debu Tripathy. Pre/perimenopausal (preMeno) women receiving palbociclib (PAL) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) in a real-world setting: Treatment patterns from POLARIS [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-19.
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems.According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib.The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs.Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.
A rolling bearing is an important part of rotating machinery, and it is widely used in the petrochemical industry, aerospace industry and other industries. Hence, it is of great significance to carry out condition monitoring and fault alarms for rolling bearings. Aiming at the problem of the rolling bearing fault, a method of an improved deep convolutional denoising auto encoder abnormal feature extraction and the Kullback-Leibler divergence threshold alarm is proposed. The experiment verification is carried out on the rotor bearing experiment platform. The experiment results show that the proposed method has good denoising performance and micro fault feature extraction ability under the condition of no fault data training and no frequency domain transformation. High accuracy, good efficiency and strong robustness of the proposed method for an early fault alarm are demonstrated by the experiment as well.
The cross roller guide has been widely used in precision machinery, such as machine tools, and contact stiffness is an important performance index of the cross roller guide. However, no report can be found on modeling about the contact stiffness of the cross roller guide. In this study, a theoretical model for the static stiffness of cross roller guide with five degrees of freedom was established. On the basis of the Hertzian line contact theory and the Boussinesq solution of elasticity theory, the function expressions of contact force and moment between the roller and the raceway were derived using the slicing method. On this basis, the guide deformation compatible equation, physical equation, and force equilibrium equation of the guide were established, and the static stiffness of the cross roller guide with degrees of freedom was obtained by iteratively solving the equations. Then, a test rig was developed to measure the static stiffness of the cross roller guide, and the proposed model was verified by comparing the experimental data with the theoretical results. Further analysis regarding the effect of preload on the displacement and stiffness of the cross roller guide was conducted, which lays a theoretical foundation for the preload adjustment of the cross roller guide.
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