scholarly journals Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome

2021 ◽  
Author(s):  
Aaron T. Gerds ◽  
Bart L Scott ◽  
Peter L. Greenberg ◽  
Tara L. Lin ◽  
Daniel A Pollyea ◽  
...  
Keyword(s):  
Adverse Event ◽  
Myelodysplastic Syndrome ◽  
Clinical Benefit ◽  
Death Rate ◽  
Single Agent ◽  
Early Death ◽  
Phase Ib ◽  
High Death Rate ◽  
High Death ◽  
Poor Efficacy

We present here primary results from the phase Ib GO29754 study (NCT02508870) evaluating the safety and tolerability of atezolizumab, a PD-L1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). R/R MDS patients received atezolizumab for 12 months (Cohort A), or atezolizumab plus azacitidine for six cycles followed by atezolizumab as maintenance for eight cycles (Cohort B). HMA-naïve MDS patients received atezolizumab plus azacitidine until loss of clinical benefit (Cohort C). Safety, activity, and exploratory endpoints were investigated. Forty-six patients were enrolled and received treatment (11 in Cohort A, 14 in Cohort B, 21 in Cohort C). All patients experienced ≥1 adverse event (AE) on study, and all patients discontinued atezolizumab. In Cohort A, seven patients (63.6%) died, and no patients responded. In Cohort B, eight patients (57.1%) discontinued azacitidine, 11 patients (78.6%) died, and two patients (14.3%) responded. In Cohort C, all 21 patients discontinued azacitidine, 13 patients died (61.9%), and 13 patients (61.9%) responded. The study was terminated by the sponsor prior to completing recruitment due to the unexpected high early death rate in Cohort C (6/13 deaths [46.2%] were due to AEs and occurred within the first four treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS.

A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11534-11534
Author(s):  
Cesar Serrano ◽  
Claudia Valverde ◽  
Josefina Cruz Jurado ◽  
Javier Martinez-Trufero ◽  
Xavier Guri ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Nuclear Export ◽  
Single Agent ◽  
Progression Free Survival ◽  
Antitumoral Activity ◽  
Clinical Activity ◽  
Activity Data ◽  
Phase Ib ◽  
Best Response ◽  
Heavily Pretreated

11534 Background: KIT or PDGFRA oncogenic activation drives GIST progression throughout the disease course. Accordingly, currently approved agents in metastatic GIST focus on the therapeutic suppression of these receptors. However, the clinical benefit after imatinib (IM) progression is still modest, suggesting the co-operation of KIT/PDGFRA-independent mechanisms in GIST cell survival. Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, and preclinical studies evidenced antitumoral activity in GIST as single agent and in combination with IM in both IM-sensitive and IM-resistant models. Methods: The phase Ib portion studied IM 400 mg daily plus weekly selinexor in patients (pts) with IM-resistant, advanced GIST. Prior intolerance to IM was not allowed. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Investigator-assessed response was evaluated every 8 weeks using RECIST 1.1. Results: At data cutoff of Sep 25, 2020, 12 pts were enrolled and received treatment with IM 400 mg and selinexor once weekly at dose levels (DL) 1 (60 mg), DL2 (80 mg) and DL3 (100 mg). Median age 57 (range 46-77), 42% female, median prior therapies 4 (range 2-7). Although only 1/6 pts developed a dose limiting toxicity (DLT) at DL3, the RP2D was defined at DL2 (IM 400 mg daily and selinexor 80 mg once weekly) based on activity data in the DL2 and the need for dose reductions in 5/6 pts at DL3 after the DLT window. All pts were evaluable for toxicity and response. One DLT occurred at DL3 (G3 nausea). Non-DLT G3/4 toxicities were anemia (1/12 pts), neutropenia (1/12 pts), vomiting (1/12 pts) and fatigue (2/12 pts). Common G1/2 toxicities were nausea (11/12 pts), vomiting (10/12 pts), neutropenia (5/12 pts) and anemia, fatigue, diarrhea, and periorbital edema (4/12 pts each). No unexpected toxicities were observed. Overall response rate in the 12 pts evaluable for response was 67% (95% CI 0.349-0.901), with 2 pts achieving PR (17%) and 6 pts SD (50%) as the best response. Clinical benefit rate (CBR = CR, PR, SD) ≥ 16 weeks was 42% (95% CI 0.157-0.723). Median progression free survival was 3.5 months (95% CI 1.7-7.3). Four pts remain on trial at data cutoff. Conclusions: IM and selinexor combination is well-tolerated and has clinical activity in heavily pretreated GIST pts. The trial is currently exploring selinexor as single agent in the IM-resistant GIST population. Clinical trial information: NCT04138381.

scholarly journals Causes of spontaneous death and euthanasia in dogs: A background study in Bahia, Brazil

2021 ◽  
Vol 66 (No. 4) ◽  
pp. 156-166
Author(s):  
JL Freitas ◽  
TS Andrade ◽  
ES Martins Filho ◽  
CS D’Soares ◽  
ACSN Souza ◽  
...  
Keyword(s):  
Death Rate ◽  
Northeast Brazil ◽  
Disease Category ◽  
Pathology Laboratory ◽  
High Death Rate ◽  
High Death ◽  
Veterinary Pathology ◽  
Diagnostic Capabilities ◽  
Health Programmes ◽  
Epidemiological Information

Understanding the causes of death in dogs enhances the diagnostic capabilities of veterinarians, as well as reduces animal mortality. Studies on this topic assist in the control and prophylaxis of epidemics and in structuring public health programmes. In total, 1 355 necropsy reports of dogs filed at the Veterinary Pathology Laboratory of the Federal University of Bahia, Northeast, Brazil (2005–2017) were analysed. The epidemiological information and anatomopathological diagnoses were obtained. The diagnosed diseases were classified into 10 categories. The frequency of the zoonoses, the overall age of the death (AD) of the dogs, and the AD of the dogs for each disease category were determined. Infectious and parasitic diseases were the most frequent primary causes of death in puppies (44.62%) and adult dogs (26.52%). In elderly dogs, most deaths occurred due to neoplasms (42.37%). Distemper (10.46%) was the most prevalent condition. A high frequency of zoonoses (6.12%) and a high death rate caused by diseases that could have been prevented (15.06%), such as distemper, parvovirus and canine visceral leishmaniasis, were reported. The AD in the population studied was eight years. The results confirmed the hypothesis of a high death rate in dogs in the state of Bahia, Northeast, Brazil, because of preventable infectious diseases.

scholarly journals DECLARATION OF EPIDEMIC PUBLIC HEALTH WITH NOVEL CORONAVIRUS

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Rafid A. Abdulkareem
Keyword(s):  
Public Health ◽  
Early Detection ◽  
Diagnostic Tests ◽  
Death Rate ◽  
Rna Viruses ◽  
Virus Disease ◽  
Respiratory Problems ◽  
High Death Rate ◽  
High Death ◽  
Novel Coronavirus

Coronaviruses (CoV) are broad enveloped RNA viruses in humans and animals are mostly correlated with enteric and respiratory problems. Within the last decades, incidents of high death rate triggered by the spread of CoV from animals to humans have occurred. Certain pathogen city of CoV is known species-dependent as with the extent of infection; Complications typically appear in closely associated human hosts. Epidemiologists assume that the SARS virus arose in bats (natural reservoirs hosts) that were transferred to persons in Wuhan, China. Presently, the available diagnostic tests are aimed at the traditional early detection of the causes of pneumonia, promote disease prevention efforts and collaborate with research laboratories that can conduct pan coronavirus detection or controlled sequencing. No vaccine is sufficient to protect toward coronaviruses. Also there is no clear treatment for corona virus disease. Patients take comprehensive medication in clinics and typically heal on their own after several times. A vaccine can take up to 45 months to develop. Let’s stay safe during this period of time. Keywords: Coronaviruses, Spreading, bats, diagnostic, vaccine

Inquiry found surgeon had high death rate for operation

BMJ ◽  
1998 ◽  
Vol 316 (7144) ◽  
pp. 1553-1553 ◽  
Author(s):  
C. Dyer
Keyword(s):  
Death Rate ◽  
High Death Rate ◽  
High Death

Portraits in Stone

2017 ◽  
Author(s):  
Jennifer Van Horn
Keyword(s):  
South Carolina ◽  
Social Network ◽  
Death Rate ◽  
High Death Rate ◽  
High Death ◽  
Stone Carvers

Elite residents of Charleston, South Carolina, sought a unique means of memorializing their dead: gravestones embellished with bust-length depictions of the deceased. Commissioned from stone carvers in Boston, these portrait gravestones reimagined the small, ivory form of the portrait miniature at a public scale suitable for the cemetery. This chapter examines why Charlestonians patronized this type of memorial, tying the gravestones to residents’ horror at the savagery unleashed upon corpses by putrefaction and to their desire to preserve bodies’ former politeness. Considering portrait gravestones along with mourning rituals and coffin construction illuminates the stones’ role as protective containers that kept savagery at bay, an important function given Charleston’s high death rate and steamy climate. Recognizing the memorials’ similarity to boundary markers, such as those erected to mark the Mason Dixon line, illuminates how the gravestones demarcated a space of colonial control. By erecting stone portraits of civil persons, Charlestonians created a social network with incredible permanence.

scholarly journals WeReview: CRISPR Tools—Live Repository of Computational Tools for Assisting CRISPR/Cas Experiments

2019 ◽  
Vol 6 (3) ◽  
pp. 63 ◽  
Author(s):  
Torres-Perez ◽  
Garcia-Martin ◽  
Montoliu ◽  
Oliveros ◽  
Pazos
Keyword(s):  
Fast Moving ◽  
Death Rate ◽  
Scientific Literature ◽  
Computational Tools ◽  
Guide Rna ◽  
Comprehensive List ◽  
High Death Rate ◽  
High Death ◽  
On Line ◽  
Rapid Pace

Computational tools are essential in the process of designing a CRISPR/Cas experiment for the targeted modification of an organism’s genome. Among other functionalities, these tools facilitate the design of a guide-RNA (gRNA) for a given nuclease that maximizes its binding to the intended genomic site, while avoiding binding to undesired sites with similar sequences in the genome of the organism of interest (off-targets). Due to the popularity of this methodology and the rapid pace at which it evolves and changes, new computational tools show up constantly. This rapid turnover, together with the intrinsic high death-rate of bioinformatics tools, mean that many of the published tools become unavailable at some point. Consequently, the traditional ways to inform the community about the landscape of available tools, i.e., reviews in the scientific literature, are not adequate for this fast-moving field. To overcome these limitations, we have developed “WeReview: CRISPR Tools,” a live, on-line, user-updatable repository of computational tools to assist researchers in designing CRISPR/Cas experiments. In its web site users can find an updated comprehensive list of tools and search for those fulfilling their specific needs, as well as proposing modifications to the data associated with the tools or the incorporation of new ones.

High death rate from neoplasms in French diabetic and non-diabetic men

The Lancet ◽  
1998 ◽  
Vol 351 (9114) ◽  
pp. 1512
Author(s):  
B Balkau ◽  
M-A Charles ◽  
E Eschwége
Keyword(s):  
Death Rate ◽  
High Death Rate ◽  
High Death

Comparison of Clinical Results between GDC Treatment and Direct Surgery for Ruptured Cerebral Aneurysms

1999 ◽  
Vol 5 (1_suppl) ◽  
pp. 207-210
Author(s):  
K. Fukui ◽  
M. Miyazaki ◽  
K. Hattori ◽  
H. Osawa ◽  
S. Miyachi ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Glasgow Outcome Scale ◽  
Death Rate ◽  
Cerebral Aneurysms ◽  
Clinical Results ◽  
Acute Stage ◽  
Clinical Grade ◽  
Systemic Complication ◽  
High Death Rate ◽  
High Death

We present a comparison of clinical results between GDC treatment and direct surgery for ruptured cerebral aneurysms. From May 97 to April 98, 32 aneurysms were treated by direct surgery (DS) or GDC treatment. Treatments were selected depending on the clinical grade, degree of hematoma and anatomical aspect of the aneurysms. There were 13 GDC treated cases and 19 direct surgery cases. In GDC cases, there were acute stage embolization for ruptured basilar aneurysm, recurrence of case after clipping for BA-SCA aneurysm, advanced age cases, and systemic complication cases. Glasgow outcome scale (GOS) in GDC cases were 8 GR, 2 MD and 3 SD. GOS in direct surgery cases were 7 GR, 4 MD, 4 SD and 4 deaths. Cases of severe subarachnoid hemorrhage with hematoma influenced the high death rate in direct surgery group. There were three complications associated with the procedure in the GDC group, however, the rate improved after advancement of the procedure. In conclusion, GDC treatment for ruptured cerebral aneurysm was satisfactorily acceptable compared to the results of direct surgery, however, more cases will be needed for precise comparison.

High death rate in mice treated topically with diclofenac

2011 ◽  
Vol 20 (4) ◽  
pp. 336-338 ◽  
Author(s):  
Catharina M. Lerche ◽  
Peter A. Philipsen ◽  
Thomas Poulsen ◽  
Hans Christian Wulf
Keyword(s):  
Death Rate ◽  
High Death Rate ◽  
High Death

Observations on the Life History of Laemophloeus minutus (Ol.) (Col. Cucujidae) when bred on various Stored Cereals and Cereal Products

1954 ◽  
Vol 45 (2) ◽  
pp. 341-350 ◽  
Author(s):  
Gwyneth C. Williams
Keyword(s):  
Life History ◽  
Adult Development ◽  
Death Rate ◽  
Fourth Instar ◽  
Cereal Products ◽  
High Death Rate ◽  
High Death ◽  
History Of ◽  
Newly Hatched Larvae ◽  
Maize Germ

Laemophloeus minutus (Ol.) has been reared on six food materials of a type with which the genus, Laemophloeus, is commonly associated in the field. Consideration of the length of egg to adult development, together with the mortality, recorded from each medium indicates that Manitoba wheat and whole-meal flour are equally favourable for the development of the species, followed in order of precedence by Plate maize, English wheat and, finally, National (85 per cent. extraction) and Canadian (70–75 per cent. extraction) flour which proved equally unfavourable.The stage of the life-history at which mortality mainly occurred varied with the diet. The high death-rate on English wheat was caused by the inability of newly hatched larvae to enter grains undamaged in the germ region. Mortality on National and Canadian flour occurred chiefly in the fourth instar.There were indications of cannibalism in both larval and adult stages, at any rate when the diet was unfavourable.The germ of wheat was attacked in preference to any other part of the grain. Maize germ was also consumed but whether it was preferred to the same extent as that of wheat was not established.Pupation was mainly, but not exclusively, intergranular in wheat. Normal cocoons were formed in National and Canadian flours but some larvae pupated in loose webbing or in flour free from webbing and freshly emerged adults were observed in unwebbed National and Canadian flour.

Sign in / Sign up

Export Citation Format

Share Document