scholarly journals Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

2021 ◽  
Vol 8 ◽  
Author(s):  
Stephen A. Klassen ◽  
Jonathon W. Senefeld ◽  
Katherine A. Senese ◽  
Patrick W. Johnson ◽  
Chad C. Wiggins ◽  
...  
Keyword(s):  
Survival Data ◽  
Survival Benefit ◽  
Patient Survival ◽  
Disease Outbreaks ◽  
Disease Course ◽  
Plasma Transfusion ◽  
Plasma Therapy ◽  
Kaplan Meier ◽  
Multiple Levels ◽  
Survival Plot

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

Insights for Quantifying the Long-Term Benefit of Immunotherapy Using Quantile Regression

2021 ◽  
pp. 173-176
Author(s):  
Bassirou Mboup ◽  
Christophe Le Tourneau ◽  
Aurélien Latouche
Keyword(s):  
Quantile Regression ◽  
Survival Data ◽  
Survival Benefit ◽  
Delayed Treatment ◽  
Kaplan Meier ◽  
Therapeutic Class ◽  
Tumor Types ◽  
Term Response ◽  
Term Benefit

PURPOSE Immunotherapy has been approved to treat many tumor types. However, one characteristic of this therapeutic class is that survival benefit is due to late immune response, which leads to a delayed treatment effect. Quantifying the benefit, if any, of such treatment, will thus require other metrics than the usual hazard ratio and different approaches have been proposed to quantify the long-term response of immunotherapy. METHOD In this paper, we suggest to use quantile regression for survival data to quantify the long-term benefit of immunotherapy. Our motivation is that this approach is not trial-specific and provides clinically understandable results without specifying arbitrary time points or the necessity to reach median survival, as is the case with other methods. We use reconstructed data from published Kaplan-Meier curves to illustrate our method. RESULTS On average, patients from the immunotherapy group have 60% chance to survive 5.46 months (95% CI, 2.57 to 9.02) more than patients in the chemotherapy group.

scholarly journals Analysis of the Expression of Cell Division Cycle-Associated Genes and Its Prognostic Significance in Human Lung Carcinoma: A Review of the Literature Databases

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Chongxiang Chen ◽  
Siliang Chen ◽  
Lanlan Pang ◽  
Honghong Yan ◽  
Ma Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Division ◽  
Survival Data ◽  
Patient Survival ◽  
Prognostic Significance ◽  
Cell Division Cycle ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Genes Expression ◽  
Kaplan Meier Plotter

Background. Lung cancer (LC) has become the top cause responsible for cancer-related deaths. Cell division cycle-associated (CDCA) genes exert an important role in the life process. Dysregulation in the process of cell division may lead to malignancy. Methods. Transcriptional data on CDCA gene family and patient survival data were examined for lung cancer (LC) patients from the GEPIA, Oncomine, cBioPortal, and Kaplan–Meier Plotter databases. Results. CDCA1/2/3/4/5/7/8 expression levels were higher in lung adenocarcinoma tissues, and the CDCA1/2/3/4/5/6/7/8 expression levels were increased in squamous cell LC tissues compared with those in noncarcinoma lung tissues. The expression levels of CDCA1/2/3/4/5/8 showed correlation with tumor classification. The Kaplan–Meier Plotter database was employed to carry out survival analysis, indicating that increased CDCA1/2/3/4/5/6/7/8 expression levels were obviously related to poor overall survival (OS) and progression-free survival (PFS) (P<0.05). Only LC patients with increased CDCA3/4/5/8 expression were significantly related to lower post-progression survival (PPS) (P<0.05). The following processes were affected by CDCA genes’ alteration: R-HAS-2500257: resolution of sister chromatid cohesion; GO:0051301: cell division; CORUM: 1118: chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB, and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: the PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression, all of which were remarkably modulated since the alterations affected CDCA genes. Conclusions. Upregulated CDCA genes’ expression levels in LC tissues probably play a crucial part in LC oncogenesis. The upregulated CDCA genes’ expression levels are used as the potential prognostic markers to improve patient survival and the LC prognostic accuracy. CDCA genes probably exert their functions in tumorigenesis through the PLK1 pathway.

scholarly journals Eye Salvage with Intra-Arterial and Intra-Vitreal Chemotherapy in Patients with Retinoblastoma: 8-Year Single-Institution Experience in Colombia

2021 ◽  
pp. 1-9
Author(s):  
María Elena González ◽  
Martha Lia Gaviria ◽  
Mariana Lópezf ◽  
Pablo Andrés Escudero ◽  
Andrés Bravo ◽  
...  
Keyword(s):  
Survival Data ◽  
Patient Survival ◽  
Secondary Treatment ◽  
Middle Income ◽  
Clinical Variables ◽  
Retrospective Assessment ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Therapeutic Alternatives ◽  
Group D

<b><i>Introduction:</i></b> Intra-arterial chemotherapy (IAC) is useful for eye preservation in advanced retinoblastoma (Rb). Intra-vitreal chemotherapy (IvitC) is the latest treatment for vitreous seeds. <b><i>Methods:</i></b> The present study is a retrospective assessment of 100 eyes, treated with primary or secondary IAC alone or with IvitC. We evaluated demographic and clinical variables, eye salvage, associated adverse events, and patient survival. Data were analyzed using descriptive statistics. Kaplan-Meier survival curves and Cox hazard ratios were utilized to assess the effect of demographic and clinical variables over eye salvage. <b><i>Results:</i></b> Bilateral Rb was observed in 61% of patients, and 57% of eyes received secondary treatment. Forty eyes needed intra-arterial plus IvitC and 62 presented advanced disease (group D and E). Three- and 5-year ocular survival probabilities were 75 and 68%. We found a higher risk in group D and E eyes and those requiring 2 or more routes for ophthalmic artery catheterization. Patients coming from other countries also showed increased risk. Using primary or secondary treatment, or IvitC, did not affect this risk. Overall rates of survival and eye salvages were 98.8 and 73%, and we had a 100% catheterization success and none ophthalmic arterial occlusions. <b><i>Conclusions:</i></b> In an upper middle-income country such as Colombia, a specialized institution counting with therapeutic alternatives and a multidisciplinary team can reach rates of patient survival and eye salvage similar to those of high-income countries.

scholarly journals EPID-36. ANTIDEPRESSANT DRUG USE IN GLIOBLASTOMA PATIENTS: AN EPIDEMIOLOGICAL VIEW

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii86-ii86
Author(s):  
Dorothee Gramatzki ◽  
James Rogers ◽  
Marian Neidert ◽  
Caroline Hertler ◽  
Emilie Le Rhun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Drug Use ◽  
Survival Data ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Methylation Status ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Population Level ◽  
Disease Course

Abstract PURPOSE Antidepressant drugs have shown anti-tumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level. METHODS Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time-frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival data and the log-rank test was performed for comparisons. RESULTS Four hundred four patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N=46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in overall survival between those patients who had taken antidepressants at some point in their disease course and those who had not (p=0.356). These data were confirmed in a multivariate analysis including age, Karnofsky performance status, gender, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (p=0.315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (p=0.639). CONCLUSIONS This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.

MO998EARLY VERSUS LATE ACUTE GRAFT PYELONEPHRITIS: A RETROSPECTIVE ANALYSIS OF GRAFT AND PATIENT OUTCOMES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anupma Kaul ◽  
Thomas Mathews
Keyword(s):  
Renal Transplant ◽  
Graft Survival ◽  
Patient Survival ◽  
Univariate Analysis ◽  
Graft Loss ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Acute Graft

Abstract Background and Aims Acute graft pyelonephritis(AGPN) is thought to affect graft and patient survival among renal transplant recipients. Our objective was to compare these outcomes in those having early AGPN(&lt;6 months from transplant) versus those having late AGPN(&gt;6months from transplant) Method This retrospective study analyzed 150 patients who had AGPN over a period of 8 years from 2005 to 2013. They were divided into early AGPN group and late AGPN group. Their baseline characteristics were compared. Predictors of graft loss and mortality were compared using logistic regression analysis. Graft survival and patient survival were analyzed using Kaplan-Meyer survival plots Results A total of 150 patients with AGPN were analyzed. Of these 55.3% (n=83) had early AGPN and 44.7% (n=67) had late AGPN. These two groups were comparable regarding baseline characteristics and immunosuppression. In early AGPN group, 13.3% (n=11) patients had CMV disease during follow up compared to 3% (n=2) in late AGPN group(p&lt;0.05). In the early AGPN group, 26.5% (n=22) had prolonged Foley’s catheterization (&gt;5days) following transplant surgery compared to 7.5% (n=5) in late AGPN group (p&lt;0.05). In the early AGPN group, 38.6% (n=32) had prolonged DJ stent in-situ (&gt;2weeks) following transplant surgery compared to 19.4% (n=13) in the late AGPN group (p&lt;0.05). Recurrent GPN was more common in the late AGPN group than the early AGPN group - 35.8% (n=24) versus 18.1% (n=15). Predictors for graft loss were assessed in patients with AGPN and the presence of renal abscess was predictive of graft loss in univariate analysis (HR-6.129, 95% CI 1.776–21.154, p-0.004). There were no significant predictors of mortality in univariate analysis. Kaplan Meier survival analysis showed decreased death censored graft survival in the early AGPN group (p-0.035). There was no Conclusion Occurrence of early AGPN had a significant impact on long term graft survival in renal transplant recipients with no significant effect on patient survival. This study underlines the paramount importance of the prevention of UTIs in renal transplant recipients.

scholarly journals SURVIVAL OF NONAGENARIAN PATIENTS WITH HIP FRACTURES: A COHORT STUDY

2017 ◽  
Vol 25 (4) ◽  
pp. 132-136 ◽  
Author(s):  
Alexa Ovidiu ◽  
Gheorghevici Teodor Stefan ◽  
Popescu Dragos ◽  
Veliceasa Bogdan ◽  
Alexa Ioana Dana
Keyword(s):  
Internal Fixation ◽  
Hip Fractures ◽  
Survival Data ◽  
Demographic Data ◽  
Level Of Evidence ◽  
Asa Score ◽  
Kaplan Meier ◽  
Trochanteric Region ◽  
One Year ◽  
Retrospective Comparative Study

ABSTRACT Objective: The objective of this study was to assess survival and factors that may influence survival in nonagenarians with hip fracture. Methods: We retrospectively analyzed 134 nonagenarian patients admitted for hip fractures over a period of 9 years, and reviewed medical records and survival data from the National Population Register. The analysis included demographic data, ASA score, surgical delay, type of treatment, and mortality. Results: Mean patient age was 92.53 years (range 90-103 years). Of the total, 35.8% of the fractures involved the femoral neck and 64.2% were in the trochanteric region. Overall mortality was 18.7% at 30 days, and 9% at one year. Mean survival for the entire sample was 683±78.1 days, with a median of 339 days; survival in men and women was 595±136.8 days and 734±94.6 days, respectively. We found that type of fracture (p=0.026) and ASA score (p=0.004) were the main factors influencing survival. Kaplan-Meier survival analysis indicated that patients with extracapsular fractures treated by internal fixation had a better survival rate (p=0.047). There was no significant differences between sexes (p = 0.102) or diagnosis (p = 0.537) Conclusion: Although nonagenarian patients have numerous comorbidities, surgical treatment using internal fixation seems superior to a conservative approach. Level of Evidence III, Retrospective Comparative Study.

Mahalanobis distance informed by clustering

2018 ◽  
Vol 8 (2) ◽  
pp. 377-406
Author(s):  
Almog Lahav ◽  
Ronen Talmon ◽  
Yuval Kluger
Keyword(s):  
Mahalanobis Distance ◽  
High Dimensional Data ◽  
Hidden Variables ◽  
Real Data ◽  
Risk Groups ◽  
High Dimensional ◽  
Data Sets ◽  
Kaplan Meier ◽  
Data Points ◽  
Survival Plot

Abstract A fundamental question in data analysis, machine learning and signal processing is how to compare between data points. The choice of the distance metric is specifically challenging for high-dimensional data sets, where the problem of meaningfulness is more prominent (e.g. the Euclidean distance between images). In this paper, we propose to exploit a property of high-dimensional data that is usually ignored, which is the structure stemming from the relationships between the coordinates. Specifically, we show that organizing similar coordinates in clusters can be exploited for the construction of the Mahalanobis distance between samples. When the observable samples are generated by a nonlinear transformation of hidden variables, the Mahalanobis distance allows the recovery of the Euclidean distances in the hidden space. We illustrate the advantage of our approach on a synthetic example where the discovery of clusters of correlated coordinates improves the estimation of the principal directions of the samples. Our method was applied to real data of gene expression for lung adenocarcinomas (lung cancer). By using the proposed metric we found a partition of subjects to risk groups with a good separation between their Kaplan–Meier survival plot.

scholarly journals 48 Immune environment correlates with NSCLC and CRC patient survival

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A55-A55
Author(s):  
Dannah Miller ◽  
Huong Nguyen ◽  
Kate Hieber ◽  
Charles Caldwell ◽  
Roberto Gianani
Keyword(s):  
T Cells ◽  
Image Analysis ◽  
Immune Cells ◽  
Survival Data ◽  
Immune Cell ◽  
Patient Survival ◽  
Machine Learning Algorithms ◽  
Primary Tumors ◽  
Cell Lung Carcinoma ◽  
Analysis Platform

BackgroundImmune cells within the tumor microenvironment (TME) play a vital role in regulating tumor progression. Therefore, immunotherapies that stimulate anti-tumor responses are of great interest for the treatment of various cancers. PD-L1 expression on immune cells is positively correlated with increased patient survival. Our hypothesis is that non-small cell lung carcinoma (NSCLC) and colorectal cancer (CRC) patients with high immune infiltration and greater amounts of anti-tumor immune cells within the tumor compartment have an increased time of survival compared to cancers with immune excluded or immune desert environments.MethodsOne NSCLC and one CRC tumor microarray (TMA) containing primary tumors, metastases, and normal tissue were stained via multiplex immunofluorescence (mIF) for 6 different immune markers: CD3, CD8, CD56, CD68, CD163, and PD-L1. This multiplex panel was designed to evaluate the immune cell population as well as tumor and immune cell PD-L1 status to aid in research for immunotherapies, specifically anti-PD-L1 therapies. The stained TMAs were analyzed utilizing Flagship Biosciences’ proprietary image analysis platform. Machine learning algorithms stratified cells as belonging to the tumoral or stromal space based on their cellular features. Core level expression data was pulled and represented on a whole-cohort basis. All staining and image analysis outputs were reviewed by a board-certified, MD pathologist. Kaplan-meier curves were generated based on survival data in relation to the levels of immune cells present within the tumor cores as well as the percentage of immune cells infiltrating into the tumor.ResultsThere is a clear correlation between patient survival and the presence or absence of various types of immune cells, including helper T cells, cytotoxic T cells, M1 macrophages, M2, macrophages, NK cells, as well as PDL1 expression on tumor and immune cells. Specifically, the increased presence of anti-tumor immune cells as well as increased expression of PD-L1 on immune cells within the tumor compartment correlates with an increase in patient survival.ConclusionsData generated through Flagship Biosciences’ image analysis platform showed a strong relationship between immune cell presence and localization and NSCLC and CRC patient survival. Altering the immune cells within the tumor to an anti-tumor immune environment could increase patient survival times. Combining immune checkpoint inhibitors with current FDA approved therapies for NSCLC and CRC are of interest to further extend patient survival. Further, utilizing Flagship Biosciences’ image analysis software to understand cancer immune microenvironments should be further utilized to aid in diagnosis and treatment decisions.

scholarly journals Convalescent Plasma Therapy in COVID 19 an Indian Scenario: Comprehensive Review

2021 ◽  
pp. 453-465
Author(s):  
Shruti Vimal ◽  
Pratiksha Naval ◽  
Manoj Sawadker ◽  
Pallavi Bhomia ◽  
Neha Jadhav ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Scientific Data ◽  
Plasma Transfusion ◽  
Eligibility Criteria ◽  
Plasma Therapy ◽  
Comprehensive Review ◽  
Proof Of Efficacy ◽  
Indian Scenario

The recent pandemic due to Corona virus more popularly known as COVID 19 has reassessed the usefulness of historic convalescent plasma transfusion. (CPT) The CPT is one of the promising therapies in the current pandemic situation. This review was conducted to evaluate the effectiveness of CPT therapy in COVID 19 patients based on the publications reported till date. PubMed, EMBASE and Medline databases were screened up to 30 April 2021. All the records were screened as per the protocol eligibility criteria.  The main features of the studies reviewed were, convalescent plasma can reduce mortality in severely ill patients, an increase in neutralizing antibodies titre and disappearance of SARS CoV 2 RNA was observed in all the patients on CPT therapy and over all a beneficial effect on clinical symptoms after administration of CP.  Based on the review findings and the limited scientific data, CPT therapy in COVID 19 patients appear safe, clinically effective and reduces mortality. However, the need of a multicentre clinical trials, unequivocal proof of efficacy, effectiveness and the need for the standardisation of the CPT needs to be addressed immediately for the full utilisation of potential of CPT.

Impact of morphine use on mortality in STEMI patients treated with primary PCI - preliminary data from a new registry

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
D Szabo ◽  
A Szabo ◽  
IF Edes ◽  
D Becker ◽  
B Merkely ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Survival Data ◽  
Preliminary Data ◽  
Laboratory Data ◽  
Rank Test ◽  
Primary Pci ◽  
Kaplan Meier ◽  
P2y12 Antagonists ◽  
Current Guidelines

Abstract Funding Acknowledgements Type of funding sources: None. Background Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use is associated with larger infarct size. Our research group presented previously, using a prospective single-center registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel. Purpose Our purpose is to check this interaction using a new registry of patients treated according to the current guidelines, including novel antiplatelet agents. Methods From May until November 2020, we collected 196 STEMI patients treated with primary PCI. 88 (44.9%) of them got morphine during the prehospital and periprocedural care. Baseline demographic, anamnestic, procedural, and laboratory data were collected. Survival data were analysed using Kaplan-Meier survival curves and the log-rank test. To adjust for confounding, a 1:1 propensity score-matching analysis was performed using 114 cases. Results An adequate balance on baseline covariates was achieved during propensity score-matching. Kaplan-Meier analysis showed no difference in 30-days mortality of the patients treated with or without morphine neither in the original nor in the propensity score-matched population (p = 0.094 and p = 0.309, respectively). Conclusion Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists. Abstract Figure. Kaplan-Meier curves

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