The impact of lymphocytosis and CD4/CD8 ratio on the anti-JCV antibody index and clinical data in patients treated with natalizumab

AbstractThe cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90–129 and 130–179 when compared to amino acids 1–89 and 200–288. Our data support variations among 90–130 as being a hotspot for sudden cardiac death and the region 131–179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90–129 and 130–180) and low risk (regions 1–89 and 200–288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification.

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Characterizing Pain Points in Clinical Data Management and Assessing the Impact of Mid-Study Updates

Therapeutic Innovation & Regulatory Science ◽

10.1007/s43441-021-00301-z ◽

2021 ◽

Author(s):

Beth Harper ◽

Zachary Smith ◽

Jane Snowdon ◽

Robert DiCicco ◽

Rezzan Hekmat ◽

...

Keyword(s):

Data Management ◽

Clinical Data ◽

The Impact ◽

Pain Points

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Project HALO: A Post-Market, Observational Registry of Data Derived from Serenity LiquidTM, Serenity GenomeTM, and Clinical Parameters (Preprint)

10.2196/preprints.31562 ◽

2021 ◽

Author(s):

Monika Hagen ◽

Danette Newton ◽

Jonathan Richina ◽

Petra Gambon Stow ◽

Jonathan Douissard

Keyword(s):

Clinical Data ◽

Clinical Course ◽

Genetic Data ◽

Data Repository ◽

Research Database ◽

Clinical Parameters ◽

Real World Setting ◽

Post Market ◽

Initial Dataset ◽

The Impact

BACKGROUND Registries are a valuable tool for data collection and observation of medical innovations in a real-world setting. Serenity LiquidTM and Serenity GenomeTM are newly launched diagnostic platforms analyzing large genetic datasets in combination with clinical data to deliver precision preventative medicine. To this point, no systematic data is available to observe the use and clinical implementations of these platforms. OBJECTIVE To create a data repository collecting data from Serenity LiquidTM, Serenity GenomeTM, and clinical parameters for analyses. METHODS Individuals receiving Serenity LiquidTM or Serenity GenomeTM are solicited to participate in this registry. In addition to the initial dataset, a clinical update is secured every six months. Data from the registry participants are pseudo-anonymized and archived in a HIPPA-compliant research database for regular analyses. RESULTS Includes but is not limited to correlations between genetic and clinical data, the impact of genetic data on the clinical course of patients, comparisons between specific cohorts (within this database and against historical cohorts) on an ongoing basis. CONCLUSIONS This is a prospective registry collecting genetic and clinical data to gather important information, provide novel insights by continuously analyzing the data in this registry.

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Impact of Hospitalized Nutritional Formula on Anthropometric, Clinical and Biochemical Indices among Egyptian Adult Cardio-Thoracic Critically Ill Patients: A Single Institutional Study

Journal of Clinical Research and Reports ◽

10.31579/2690-1919/139 ◽

2021 ◽

Vol 7 (1) ◽

pp. 01-11

Author(s):

Khalil NS

Keyword(s):

Critically Ill ◽

Clinical Data ◽

Critically Ill Patients ◽

Skin Color ◽

Admission Time ◽

Chest Disease ◽

Disease Hospital ◽

Biochemical Indices ◽

The Impact

Background: Malnutrition is a common consequence notably in patients admitted to the intensive care unit. Aim of the study: was to assess the Impact of hospitalized nutritional formula on anthropometric, clinical and biochemical indices among Egyptian adult cardio-thoracic Critically Ill Patients on admission and discharge days. Methods: Totally, A convenient sample of 100 cardiothoracic patients was evaluated from admission to discharge in ICUs at Damietta Chest Disease Hospital in Egypt. The patients' anthropometric measurements, clinical data and biochemical indices were assessed As well, hospital diet prescription and intake was also evaluated. Results: High significant statistical difference patients' clinical data on admission and after one week such as body built (X2 = 52.6; p = 0.0), skin color (X2= 12.9; p = 0.02), skin turgor (X2= 13.19; p = 0.0), and occurrence of bed sore (X2= 27.7; p = 0.0). On the other hand, no significant statistical differences were found in the patients' weight and body mass index on admission and discharge (one week). Moreover, significant statistical differences were found in patients biochemical indices such as albumin (t= 3.03; p=0.003) and lymphocyte counts (3.74; p=0.000). So, the 88 % of patients showed decreased albumin after one week when compared to admission time. While, 10 % of patients showed increased lymphocytic count after one week of admission when compared to admission time. Conclusion and Recommendations: Clinical assessment, anthropometric, and biochemical indices are essential for evaluation, follow-up and management of cardiothoracic critically ill patients

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Secondary hemorrhagic complications in aneurysmal subarachnoid hemorrhage: when the impact hits hard

Journal of Neurosurgery ◽

10.3171/2018.9.jns182105 ◽

2020 ◽

Vol 132 (1) ◽

pp. 79-86 ◽

Cited By ~ 3

Author(s):

Marvin Darkwah Oppong ◽

Kathrin Buffen ◽

Daniela Pierscianek ◽

Annika Herten ◽

Yahya Ahmadipour ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Antiplatelet Therapy ◽

Clinical Data ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Final Analysis ◽

Minor Bleeding ◽

Thrombolytic Agents ◽

Poor Outcome ◽

Hemorrhagic Complications ◽

The Impact

OBJECTIVEClinical data on secondary hemorrhagic complications (SHCs) in patients with aneurysmal subarachnoid hemorrhage (SAH) are sparse and mostly limited to ventriculostomy-associated SHCs. This study aimed to elucidate the incidence, risk factors, and impact on outcome of SHCs in a large cohort of SAH patients.METHODSAll consecutive patients with ruptured aneurysms treated between January 2003 and June 2016 were eligible for this study. Patients’ charts were reviewed for clinical data, and imaging studies were reviewed for radiographic data. SHCs were divided into those associated with ventriculostomy and those not associated with ventriculostomy, as well as into major and minor bleeding forms, depending on clinical impact.RESULTSSixty-two (6.6%) of the 939 patients included in the final analysis developed SHCs. Ventriculostomy-associated bleedings (n = 16) were independently predicted by mono- or dual-antiplatelet therapy after aneurysm treatment (p = 0.028, adjusted odds ratio [aOR] = 10.28; and p = 0.026, aOR = 14.25, respectively) but showed no impact on functional outcome after SAH. Periinterventional use of thrombolytic agents for early effective anticoagulation was the only independent predictor (p = 0.010, aOR = 4.27) of major SHCs (n = 38, 61.3%) in endovascularly treated patients. In turn, a major SHC was independently associated with poor outcome at the 6-month follow-up (modified Rankin Scale score > 3). Blood thinning drug therapy prior to SAH was not associated with SHC risk.CONCLUSIONSSHCs present a rare sequela of SAH. Antiplatelet therapy during (but not before) SAH increases the risk of ventriculostomy-associated bleedings, but without further impact on the course and outcome of SAH. The use of thrombolytic agents for early effective anticoagulation carries relevant risk for major SHCs and poor outcome.

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The Impact of New and Emerging Clinical Data on Treatment Strategies for Atrial Fibrillation

Journal of Cardiovascular Electrophysiology ◽

10.1111/j.1540-8167.2010.01770.x ◽

2010 ◽

pp. no-no ◽

Cited By ~ 4

Author(s):

ERIC N PRYSTOWSKY ◽

JOHN CAMM ◽

GREGORY Y.H. LIP ◽

MAURITS ALLESSIE ◽

JEAN-FRANÇOIS BERGMANN ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Data ◽

Treatment Strategies ◽

The Impact

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Use of chemotherapy (CT) in BRCA1/2-deficient ovarian cancer (BDOC) patients (pts) with poly-ADP-ribose polymerase inhibitor (PARPi) resistance: A multi-institutional study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5022 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5022-5022 ◽

Cited By ~ 1

Author(s):

Joo Ern Ang ◽

Charlie Gourley ◽

Hilda Anne High ◽

Ronnie Shapira-Frommer ◽

C. Bethan Powell ◽

...

Keyword(s):

Clinical Data ◽

Cox Regression ◽

Progression Free Survival ◽

Resistance Rate ◽

Free Survival ◽

Predictors Of Response ◽

Single Centre Study ◽

Polymerase Inhibitor ◽

Brca1 Brca2 ◽

The Impact

5022 Background: Emerging clinical data point to the clinical utility of PARPi in BDOC. However, the impact of PARPi exposure on the prospects of response to further CT remains unclear. In our previous single centre study, we provided the first clinical data relating to the use of post-PARPi CT (JCO 2010: 28(15S), A5041). Our aim here was to re-examine this issue in a larger multi-institutional population. Methods: We included pts with advanced BDOC who received CT, having progressed on ≥200 mg bd olaparib. Pt, tumor and treatment characteristics and clinical outcomes were documented. Relationships between post-PARPi CT overall survival (OS) and other variables were explored using Cox regression. Results: We collected data on 75 pts (median age 51 y [range 31-77], BRCA1:BRCA2 54:21, mean 3 previous lines of CT [95% CI 2.5-3.4], pre-PARPi platinum (Plt) resistance rate 49% and olaparib RECIST-response rate [RR] 39% [95% CI 28-50]). Following olaparib, most pts received Plt alone or in combination with taxane (Tx) or liposomal doxorubicin (PLD). Weekly Plt was used in 36% of all Plt-treated pts, mainly in combination with weekly Tx. Overall RECIST and CA125 (GCIG) RRs were 38% and 48%, respectively; these responses occurred independently of PARPi response or pre-PARPi Plt sensitivity (all p>.1). The median progression free survival and OS of RECIST responders were 7.9 m (95% CI 5.8-10.9) and 10.5 m (95% CI 1.4-19.6), respectively. In all pts, the median OS from the start of post-PARPi CT was 7.9 m (95% CI 5.7-10.1) while that from diagnosis was 64.9 m (95% CI 52.9-76.9). Factors associated with improved OS on post-PARPi CT in the MVA included best olaparib response of non-disease progression (p=.003, HR 0.28), optimal initial debulking (p=.01, HR 0.36) and pre-PARPi Plt sensitivity (p=.05, HR 0.46). Conclusions: These data indicate potential for meaningful responses to CT in BDOC pts with PARPi resistance. Analysis to identify molecular predictors of response is ongoing. [Table: see text]

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Expanded molecular routine testing for targetable mutations in non-small cell lung cancer to reveal frequent co-occuring mutations.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20596 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20596-e20596

Author(s):

Anna Kostenko ◽

Jana Fassunke ◽

Susanne Steinhauser ◽

Matthias Scheffler ◽

Sabine Merkelbach-Bruse ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Molecular Diagnostics ◽

Clinical Data ◽

Single Gene ◽

Genomic Medicine ◽

Genetic Alterations ◽

Clinical Diagnostics ◽

Central Platform ◽

The Impact

e20596 Background: Using next-gen sequencing of predefined gene panels in routine clinical diagnostics of lung cancer allows, in contrast to single-gene assays, assessment of co-occuring mutations, which might underly heterogeneity of response to targeted drugs and survival. The Network Genomic Medicine (NGM) performs high sensitive next generation sequencing (NGS) based routine molecular diagnostics on a central platform for about 5000 inoperable lung cancer patients (pts) annually in Germany. Methods: NGS panel used in NGM consists of 17 genes to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, while FISH analyses were performed separately. In 2016, we have started the evaluation of all NGM pts with available clinical data who had received NGS-based molecular diagnostics. In particular, we have focused on non-squamous (non-sq) and squamous (sq) NSCLC pts with co-occurring mutations: their frequency, significance and impact on overall survival. Results: From 2014 molecular genotyping was performed for 7,893 NGM pts (n = 7,246 NSCLC (5,667 non-sq and 1,487 sq pts) and n = 489 SCLC) with eligible clinical data. Genetic alterations in transformation-associated pathways were found in 79 % of all NSCLC pts. Furthermore, co-occurring mutations were detected in 39 % of these pts: 40 % in non-sq and 37 % in sq NSCLC. 11 % of pts had more than 2 co-occurring mutations. 1 % of all pts had 5 co-occurring mutations. The most frequent paired mutations were KRAS, EGFR and MET each with TP53 in non-sq and FRGF1 and TP53 in sq NSCLC. The incidences and significance of 3, 4 and 5 co-mutations as well as the impact of these co-occurring mutations on overall survival will be presented. Conclusions: Frequent occurrence of co-occuring mutations in transformation – associated pathways underlines the genetic heterogeneity also of lung cancer with classical driver mutation and the impact of co-occurring mutations on survival. This work confirms the use of molecular multiplex testing in routine molecular diagnostics of NSCLC. Assessment of co-occuring mutations will help to further specify genetically defined subgroups of lung cancer with therapeutic relevance.

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Variations in inpatient stays for non-metastatic HER2- breast cancer (BC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) in a real world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18099 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18099-e18099

Author(s):

Jennifer Malin ◽

Stacey DaCosta Byfield ◽

Benjamin Chastek ◽

Stephanie Korrer ◽

Thomas Horstman ◽

...

Keyword(s):

Clinical Data ◽

Claims Data ◽

Administrative Claims ◽

Cancer Type ◽

Prior Authorization ◽

Inpatient Stay ◽

Her2 Breast Cancer ◽

Real World Setting ◽

End Of Treatment ◽

The Impact

e18099 Background: We aim to compareprevalence and duration of inpatient stays during the most commonly used chemotherapy regimens for BC, NSCLC, and CRC in a commercially insured population. Methods: This analysis used clinical data obtained from a prior authorization program for chemotherapy linked with administrative claims data from 6/1/2015 to 5/31/2016. Clinical data included cancer type, stage at diagnosis, relevant biomarkers, and evidence of progression/relapse. Eligible patients included commercially insured members with a prior authorization request for one of the most commonly used NCCN recommended regimens for BC, NSCLC and CRC. Outcomes, including percent of patients experiencing an inpatient stay and number of inpatient days were tracked from the first claim for chemotherapy until end of treatment due to discontinuation, death or change in treatment, with remaining patients censored at 5/31/2016 or end of enrollment. Results: There were 1612 HER2- BC, 237 NSCLC, and 386 CRC patients who completed therapy during the study period. Incidence and inpatient stay days per 100 patient months for the most common regimens for each cancer are summarized in the table. Conclusions: The rates and duration of inpatient stays varied substantially across the most commonly used therapies for BC, NSCLC and CRC. These data show the importance of systematically incorporating the impact of hospitalizations alongside other clinical outcomes in treatment choice in routine clinical practice. As the database grows over time, these data will help clinicians and patients better evaluate regimen choices for various cancers. [Table: see text]

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