Early stopping designs based on progression-free survival at an early time point in the initial cohort

2007 ◽  
Vol 26 (24) ◽  
pp. 4400-4415 ◽  
Author(s):  
Samuel Litwin ◽  
Yu-Ning Wong ◽  
Gary Hudes
Keyword(s):  
Early Time ◽  
Progression Free Survival ◽  
Early Stopping ◽  
Early Time Point ◽  
Free Survival ◽  
Initial Cohort ◽  
Time Point

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

Salt induced programmed cell death in rice: evidence from chloroplast proteome signature

2021 ◽  
Vol 48 (1) ◽  
pp. 8
Author(s):  
Vivek Ambastha ◽  
Sudhir K. Sopory ◽  
Baishnab C. Tripathy ◽  
Budhi Sagar Tiwari
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Early Time ◽  
Biological Functions ◽  
Rice Seedlings ◽  
Early Time Point ◽  
Phosphorylation Pattern ◽  
Moderate Salinity ◽  
Chloroplast Proteome ◽  
Time Point

Soil salinity, depending on its intensity, drives a challenged plant either to death, or survival with compromised productivity. On exposure to moderate salinity, plants can often survive by sacrificing some of their cells ‘in target’ following a route called programmed cell death (PCD). In animals, PCD has been well characterised, and involvement of mitochondria in the execution of PCD events has been unequivocally proven. In plants, mechanistic details of the process are still in grey area. Previously, we have shown that in green tissues of rice, for salt induced PCD to occur, the presence of active chloroplasts and light are equally important. In the present work, we have characterised the chloroplast proteome in rice seedlings at 12 and 24 h after salt exposure and before the time point where the signature of PCD was observed. We identified almost 100 proteins from chloroplasts, which were divided in to 11 categories based on the biological functions in which they were involved. Our results concerning the differential expression of chloroplastic proteins revealed involvement of some novel candidates. Moreover, we observed maximum phosphorylation pattern of chloroplastic proteins at an early time point (12 h) of salt exposure.

scholarly journals Equivalent tumor detection for early and late FAPI-46 PET acquisition

2021 ◽  
Author(s):  
J. Ferdinandus ◽  
L. Kessler ◽  
N. Hirmas ◽  
M. Trajkovic-Arsic ◽  
R. Hamacher ◽  
...  
Keyword(s):  
Early Time ◽  
Tumor Detection ◽  
University Hospital ◽  
Late Time ◽  
Early Time Point ◽  
Positron Emission ◽  
Organ Uptake ◽  
Significant Difference ◽  
Late Time Point ◽  
Time Point

Abstract Introduction Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. Methods This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). Results In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: − 0.48, − 0.14, − 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03). Conclusion In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Primo Lara ◽  
Laurel Beckett ◽  
Yueju Li ◽  
Mamta Parikh ◽  
Daniel Robles ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Organ Function ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Initial Cohort ◽  
Secondary Endpoints ◽  
Anti Tumor Activity ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, & 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), & neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 & 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.

scholarly journals Targeted Nanoprobes Reveal Early Time Point Kinetics In Vivo by Time-Resolved MRI

Theranostics ◽  
2011 ◽  
Vol 1 ◽  
pp. 274-276 ◽  
Author(s):  
Ashwinkumar Bhirde ◽  
Ning Guo ◽  
Xiaoyuan Chen
Keyword(s):  
Early Time ◽  
Early Time Point ◽  
Time Resolved ◽  
Point Kinetics ◽  
Kinetics In Vivo ◽  
Time Point

scholarly journals Oral bacteriophages are maintained at high levels for months in individuals but infrequently transmitted between mothers and infants

2019 ◽  
Author(s):  
Clifford J. Beall ◽  
Rosalyn M. Sulyanto ◽  
Ann L. Griffen ◽  
Eugene J. Leys
Keyword(s):  
Oral Cavity ◽  
Nucleotide Diversity ◽  
Early Time ◽  
Detectable Level ◽  
First Year ◽  
Bacterial Genomes ◽  
Early Time Point ◽  
Multiple Strains ◽  
Metagenomic Assembly ◽  
Time Point

ABSTRACTIn this work, we exploit recent advances in metagenomic assembly and bacteriophage identification to describe the phage content of saliva from 5 mother-baby pairs sampled twice 7 - 11 months apart during the first year of the babies’ lives. We identify 25 phage genomes that are comprised of one to 71 contigs, with 16 having a single contig. At the detectable level, phage were sparsely distributed with the most common one being present in 4 of the 20 samples, derived from two mothers and one baby. However, if they were present in the early time point sample from an individual, they were also present in the later sample from the same person more frequently than expected by chance. The nucleotide diversity (π) in phage from the same sample or the same person was much lower than between different individuals, indicating dominance of one strain in each person. This was different from bacterial genomes, which had higher diversity indicating the presence of multiple strains within an individual. We identify likely bacterial hosts for 16 of the 25 phage, including an apparent inovirus that is capable of integrating in the dif site ofHaemophilusspecies. It appears that phage in the oral cavity are sparsely distributed, but can be maintained for months once acquired.

Abstract P430: Inflammatory Survival Gene Expression Patterns Differentiate Favorable and Unfavorable Outcomes Following Surgical Intervention in Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ifeanyi O Iwuchukwu ◽  
doan nguyen ◽  
Jasmine Warren ◽  
ALIREZA SHIRAZIAN ◽  
Vi Tran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Surgical Management ◽  
Expression Patterns ◽  
Early Time ◽  
Pcr Analysis ◽  
Early Time Point ◽  
Time Points ◽  
Arginase 1 ◽  
Anti Inflammatory ◽  
Time Point

Background and Aims: Surgical management of intracerebral (ICH) remains controversial due to unclear benefit. In this study, we analyzed temporal changes in expression of proinflammatory and anti-inflammatory survival genes to discern the molecular differences between favorable and unfavorable outcomes after surgery. Methods: Venous blood collected in Paxgene Blood RNA from ICH patients before surgery at ‘early’ (Day 0-2) and at ‘delayed’ (Day 3-5) timepoints. Extracted total RNA was used for real-time Taqman PCR analysis for anti-inflammatory, survival genes superoxide dismutase 1(SOD1), COX-2, IL-10, peroxisome proliferator activated receptor gamma (PPARG), TGF-B1, and IL-10. The pro-inflammatory genes included arginase-1 (ARG1), TNF, IL-1B, monocyte/macrophage activity markers (CD36, CD163) and NF-kB members (NFKB1, NFKB2, RELA, RELB, REL, NFKBIA). Relative fold changes were determined after normalizing to GAPDH. 90-day Modified Rankin Score (mRS) were collected and classified as favorable, mRS 0-3 (n=4) and unfavorable, mRS 4-6 (n=8). Statistical analysis was carried out by Welch’s ANOVA test (p<0.05). Results: Mean age was 56.25yrs (SD 19.7). ICH location was 10 deep nuclei (thalamus or basal ganglia), 1 cerebellum, and 1 lobar. ICH volume was lower in the mRS 0-3 group (24.15ml SD21.2 vs 35.8ml SD 31.7 p=0.68). All patients had a decompressive hemicraniectomy and 7 included hematoma evacuation. Overall, the NFkB family gene expression was increased at ‘delayed’ relative to the early time points in both groups. However, RELB expression was significantly higher at the early time point of mRS 0-3 compared to mRS 4-6 group. Expression of ARG1, SOD1, COX2, IL-1B, IL-10, TGF-B1, PPARG and CD36 increased significantly at the delayed compared to the early time point. In the unfavorable outcome group (mRS 4-6), TNF expression increased significantly at the delayed timepoints compared to mRS 0-3 which was unchanged. Conclusions: The studied genes were highly expressed and differed significantly between time points. TNF was significantly expressed at the delayed time point in the mRS 4-6 group but unchanged in the mRS 0-3 group. Further studies will explore the role of TNF and related genes in patient selection and outcomes for surgical management of ICH.

scholarly journals Essential Role of CCL2 in Clustering of Splenic ERTR-9+ Macrophages during Infection of BALB/c Mice by Listeria monocytogenes

2006 ◽  
Vol 75 (1) ◽  
pp. 462-470 ◽  
Author(s):  
Jadwiga Jablonska ◽  
Kurt E. Dittmar ◽  
Tanja Kleinke ◽  
Jan Buer ◽  
Siegfried Weiss
Keyword(s):  
Listeria Monocytogenes ◽  
Marginal Zone ◽  
Early Time ◽  
Cell Types ◽  
Host Cells ◽  
Early Time Point ◽  
Infected Cells ◽  
Different Cell Types ◽  
Time Point

ABSTRACT Early interactions between pathogens and host cells are often decisive for the subsequent course of infection. Here we investigated early events during infection by Listeria monocytogenes, a ubiquitously occurring facultative intracellular microorganism that exhibits severe pathogenicity, mainly in immunocompromised individuals. We show that the inflammatory chemokine CCL2 is highly up-regulated early after Listeria infection in spleens of BALB/c mice. ERTR-9+ macrophages of the marginal zone were identified as the only infected cells and exclusive producers of CCL2 at the early time point. Consequently, clusters of different cell types were formed around infected ERTR-9+ cells. Metallophilic MOMA-1+ marginal zone macrophages were, however, excluded from the clusters and migrated into the B-cell follicles. Depletion of CCL2 during infection resulted in a different composition of cell clusters in the spleen and increased the mortality rate of treated mice. Interestingly, ERTR-9+ macrophages no longer were part of clusters in such mice but remained at their original location in the marginal zone.

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