scholarly journals Overall reduced lymphocyte especially T and B subsets closely related to the poor prognosis and the disease severity in severe patients with COVID-19 and diabetes mellitus

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Dafeng Liu ◽  
Yong Wang ◽  
Bennan Zhao ◽  
Lijuan Lan ◽  
Yaling Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Disease Progression ◽  
Poor Prognosis ◽  
Lymphocyte Subsets ◽  
Severe Disease ◽  
Peripheral Lymphocyte ◽  
Immunomodulatory Treatment ◽  
The Poor ◽  
Trial Register ◽  
Clinical Trial Register

Abstract Background A dysregulated host immune response is common in patients with COVID-19. Aim In this study, we aimed to define the characteristics of lymphocyte subsets and their relationship with disease progression in COVID-19 patients with or without diabetes mellitus (DM). Methods The baseline peripheral lymphocyte subsets were compared between 55 healthy controls and 95 patients with confirmed COVID-19, and between severe and non-severe COVID-19 patients with or without DM. Results The prevalence of DM in the COVID-19 group was 20%, and patients with severe COVID-19 had a higher prevalence of DM than those with non-severe disease (P = 0.006). Moreover, a significantly poor prognosis and a higher rate of severity were found in those with DM relative to those without DM (P = 0.001, 0.003). Generally, all lymphocytes and subsets of lymphocytes, especially B and T cells, were significant reduced in COVID-19 patients, particularly in those with DM. Patients with severe COVID-19 and DM had the lowest lymphocyte counts compared with those with severe COVID-19 without DM, and those with non-severe COVID-19 with or without DM. Partially decreased lymphocyte subsets, age and DM were closely related to disease progression and prognosis. Conclusions These findings provide a reference for clinicians that immunomodulatory treatment may improve disease progression and prognosis of COVID-19 patients, especially those with severe disease with DM. Trial registration Chinese Clinical Trial Register ChiCTR2000034563

scholarly journals Overall Reduced Baseline Lymphocyte Subsets Closely Related to the Poor Prognosis and the Disease Severity in Patients With COVID-19 and Diabetes Mellitus

2020 ◽  
Author(s):  
Dafeng Liu ◽  
yong Wang ◽  
Bennan Zhao ◽  
Lijuan Lan ◽  
Yaling Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Response ◽  
Disease Progression ◽  
Poor Prognosis ◽  
Lymphocyte Subsets ◽  
Peripheral Lymphocyte ◽  
Control Group ◽  
Immunomodulatory Treatment ◽  
The Poor ◽  
B And T Lymphocytes

Abstract IntroductionDysregulated host immune response was common in COVID-19. In this study we aimed at the characteristics of lymphocyte subsets and its relationship with the disease progression in COVID-19 patients with or without DM.MethodsThe baseline peripheral lymphocyte and subsets were compared between 55 healthy cases (control group) and 95 confirmed cases with COVID-19 (COVID-19 group), and between COVID-19 patients with and without DM.ResultsThe prevalence of DM in COVID-19 group was 20%, and severe cases had higher the prevalence of DM than non-severe cases (P=0.006), moreover significantly poor prognosis and higher severe rate were found in those with DM relative to those without DM (P=0.001,0.003, respectively). In COVID-19 group overall and significant reduced lymphocyte and subsets, especially B and T lymphocytes were found, especially in those with DM. Partial decreased lymphocyte subsets, age and DM closely related with the disease progression and the prognosis.ConclusionsThese findings provide a reference for clinicians that immunomodulatory treatment maybe improve disease progression and prognosis of COVID-19 patients, especially those with DM.

Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCRexpression, elevated BCR-ABL levels, or karyotypic instability

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4547-4553 ◽  
Author(s):  
Brian J. P. Huntly ◽  
Anthony J. Bench ◽  
Eric Delabesse ◽  
Alistair G. Reid ◽  
Juan Li ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Prognostic Indicator ◽  
Genetic Alterations ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
The Poor

Deletions of the derivative chromosome 9 have recently been reported in chronic myeloid leukemia. These deletions are large, occur at the time of the Philadelphia (Ph) translocation, span the translocation breakpoint, and represent a powerful prognostic indicator. However, the molecular mechanisms responsible for the poor prognosis associated with deletions are obscure, and several possible models are investigated here. First, we demonstrate that all derivative chromosome 9 deletions detected by fluorescence in situ hybridization were associated with an absence ofABL-BCR expression. However, loss ofABL-BCR expression also occurred without an overt deletion, suggesting the existence of other mechanisms by whichABL-BCR transcription can be abolished. Furthermore, analysis of survival in 160 patients demonstrated that loss ofABL-BCR expression, in contrast to deletion status, was not an indicator of poor prognosis. Second, we addressed the possibility that concomitant small deletions of the Ph chromosome modulateBCR-ABL transcription. Real-time reverse-transcription polymerase chain reaction was used to demonstrate that derivative chromosome 9 deletions were not accompanied by altered levels of BCR-ABL transcripts. Third, deletions may represent a consequence of genetic instability within the target cell at the time of the Ph translocation, with the poor prognosis reflecting a predisposition to subsequent additional genetic alterations. However, patients with deletions do not exhibit an increased frequency of secondary cytogenetic changes following disease progression. Taken together, these data support a model in which deletions of the derivative chromosome 9 result in rapid disease progression as a result of the loss of one or more genes within the deleted region.

DIAGNOSTICS OF DIABETIC CARDIAC AUTONOMOUS NEUROPATHY

2021 ◽  
pp. 135-138
Author(s):  
Holupko N.V. ◽  
◽  
Mohort , T.V. ◽  
Korzhenevskaja N.I. ◽  
Benchuk N.L. ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Practice ◽  
Poor Prognosis ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Diagnostic Methods ◽  
Cardiac Autonomic Neuropathy ◽  
Clinical Implications ◽  
Diabetic Cardiac Autonomic Neuropathy

Diabetes mellitus is a severe disease that leads to an early disability and premature death. Diabetic cardiac autonomic neuropathy (DCAN) is a serious and frequent complication of diabetes mellitus with a poor prognosis. Timely diagnosis of DCAN can have important clinical implications, since DCAN is an independent risk factor for cardiovascular mortality, arrhythmias, painless ischemia, and other cardiovascular disorders. Despite this, until now, in clinical practice, they are rarely engaged in an active search for the symptoms of DCAN and it remains a poorly studied and rarely diagnosed complication of diabetes mellitus. The article discusses the methods of detecting and assessing DACN in clinical practice, including the assessment of clinical manifestations, the use of reflex cardiovagal tests and common instrument6al diagnostic methods.

scholarly journals The Effect of Heterogenous Subregions in Glioblastomas on Survival Stratification: A Radiomics Analysis Using the Multimodality MRI

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Lulu Yin ◽  
Yan Liu ◽  
Xi Zhang ◽  
Hongbing Lu ◽  
Yang Liu
Keyword(s):  
Poor Prognosis ◽  
Intratumor Heterogeneity ◽  
Short Term ◽  
Prognostic Information ◽  
Manual Delineation ◽  
Flair Sequence ◽  
The Poor ◽  
Contrast Enhanced ◽  
Mri Sequences

Intratumor heterogeneity is partly responsible for the poor prognosis of glioblastoma (GBM) patients. In this study, we aimed to assess the effect of different heterogeneous subregions of GBM on overall survival (OS) stratification. A total of 105 GBM patients were retrospectively enrolled and divided into long-term and short-term OS groups. Four MRI sequences, including contrast-enhanced T1-weighted imaging (T1C), T1, T2, and FLAIR, were collected for each patient. Then, 4 heterogeneous subregions, i.e. the region of entire abnormality (rEA), the regions of contrast-enhanced tumor (rCET), necrosis (rNec) and edema/non-contrast-enhanced tumor (rE/nCET), were manually drawn from the 4 MRI sequences. For each subregion, 50 radiomics features were extracted. The stratification performance of 4 heterogeneous subregions, as well as the performances of 4 MRI sequences, was evaluated both alone and in combination. Our results showed that rEA was superior in stratifying long-and short-term OS. For the 4 MRI sequences used in this study, the FLAIR sequence demonstrated the best performance of survival stratification based on the manual delineation of heterogeneous subregions. Our results suggest that heterogeneous subregions of GBMs contain different prognostic information, which should be considered when investigating survival stratification in patients with GBM.

scholarly journals Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

2021 ◽  
Author(s):  
Juan Tong ◽  
Lei Zhang ◽  
Huilan Liu ◽  
Xiucai Xu ◽  
Changcheng Zheng ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Chemotherapy Group ◽  
Blood Transplantation ◽  
The Poor ◽  
First Complete Remission

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

scholarly journals SAT0330 NEW IMMUNOMODULATORY COMBINATION THERAPIES IN PATIENTS WITH SYSTEMIC SCLEROSIS: A RETROSPECTIVE CROSS-SECTIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1110.1-1111
Author(s):  
J. Qiao ◽  
S. X. Zhang ◽  
T. T. Zhang ◽  
J. Zhang ◽  
M. T. Qiu ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Side Effects ◽  
Lymphocyte Subsets ◽  
Cross Sectional Study ◽  
Peripheral Lymphocyte ◽  
High Morbidity ◽  
Combination Therapies ◽  
Sectional Study ◽  
Cross Sectional ◽  
Long Term Treatment

Background:Systemic sclerosis (scleroderma, SSc) is a rare complex connective tissue disease associated with high mortality and high morbidity1. Active SSc are typically treated with immunosuppressants, which may create a variety of severe side-effects, especially for long-term treatment2. As the pathogenesis of SSc is still a matter of debate, growing evidences have focused on the immune disorders3. However, the quantitative status of lymphocyte subsets in SSc patients are unclear and effects of immunomodulatory combination therapies (avoiding side-effects of conventional therapy) on the lymphocyte subsets are unknown.Objectives:To investigate the quantitative status of peripheral lymphocyte subpopulations and CD4+T subsets in SSc patients for the exploration of SSc pathogenesis and evaluate the effects of new immunomodulatory combination therapies on those cells.Methods:From July 2014 to December 2019, total 166 patients with SSc and 206 healthy controls (HCs) were enrolled in this study, in which, 79 follow-up patients received immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Tregs in peripheral blood of these subjects were detected by flow cytometry combined with standard absolute counting beads.Results:Patients with SSc had lower absolute counts of total T, NK, Th2, Th17 and Tregs as compared with those of HCs (P<0.05) (Figure 1). After immunomodulatory combination treatments, there were increases in a various of peripheral lymphocyte subsets such as T, B and CD8+T (P< 0.05). Moreover, the increased level of Tregs was much more dramatical than those of other lymphocyte subsets, resulting in the decrease ratios of Teffs/Tregs such as Th1/Tregs and Th2/Tregs and rebuilding immunologic equilibrium (Figure 2).Conclusion:This cross-sectional study clarified the abnormal status of lymphocyte subsets in SSc patients, suggesting lymphocyte subsets, especially Tregs, might be relevant and play a crucial role in the pathogenesis of SSc, thus providing a potential therapeutic target for SSc patients. Immunomodulatory combination therapies effectively increase the level of Tregs as well as other lymphocytes to some degree and maintain the immunologic equilibrium, which may help for SSc patients’ symptom remission.References:[1]Denton CP, Khanna D. Systemic sclerosis. Lancet 2017;390(10103):1685-99. doi: 10.1016/S0140-6736(17)30933-9 [published Online First: 2017/04/18][2]Winthrop KL, Weinblatt ME, Bathon J, et al. Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019. Ann Rheum Dis 2020;79(1):88-93. doi: 10.1136/annrheumdis-2019-216151 [published Online First: 2019/10/31][3]Skaug B, Khanna D, Swindell WR, et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Ann Rheum Dis 2019 doi: 10.1136/annrheumdis-2019-215894 [published Online First: 2019/11/27]Acknowledgments :None.Disclosure of Interests:None declared

scholarly journals Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Iannetta ◽  
Francesco Buccisano ◽  
Daniela Fraboni ◽  
Vincenzo Malagnino ◽  
Laura Campogiani ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Severe Disease ◽  
Laboratory Data ◽  
Lymphocyte Subset ◽  
Multivariable Logistic Regression Analysis ◽  
Double Positive ◽  
Increased Risk ◽  
T Lymphocyte Subset

AbstractThe aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

scholarly journals The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study

2020 ◽  
Vol 58 (7) ◽  
pp. 1106-1115 ◽  
Author(s):  
Yufen Zheng ◽  
Ying Zhang ◽  
Hongbo Chi ◽  
Shiyong Chen ◽  
Minfei Peng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Platelet Count ◽  
Disease Progression ◽  
Neutrophil Count ◽  
Calibration Curve ◽  
Lymphocyte Count ◽  
Severe Disease ◽  
Clinical Impact ◽  
Predictive Tool ◽  
Potential Biomarker

AbstractObjectivesIn December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19.MethodsIn this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy.ResultsThe data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954–10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097–0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111–0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746–0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients.ConclusionsWe designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

scholarly journals THU0070 DEFINING SYNOVIAL SIGNATURES IN THE RAT CIA MODEL: WHAT CAN WE LEARN ABOUT RA PROGRESSION?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 247.2-248
Author(s):  
D. Ruelas ◽  
R. LI ◽  
C. Franci ◽  
V. Lira ◽  
D. Lopez ◽  
...  
Keyword(s):  
Disease Progression ◽  
Synovial Tissue ◽  
Current Knowledge ◽  
Severe Disease ◽  
Unmet Need ◽  
Poor Response ◽  
Multiple Time ◽  
Combination Therapies ◽  
Course Of Disease ◽  
Time Point

Background:Patients showing inadequate or no response to current therapies represent a key unmet need in rheumatoid arthritis (RA). To address this, novel or combination therapies are of high clinical interest. Identification of novel therapeutic targets requires a greater understanding of the pathogenic molecular drivers in the RA synovium. However, our current knowledge of human molecular patterns that emerge as a result of disease progression is complicated by patient-to-patient heterogeneity and access to synovial tissue.Objectives:Here we use the current knowledge of human synovial heterogeneity to conduct a longitudinal study of global molecular responses in the rat collagen-induced arthritis (CIA) model to better understand synovial biology, improve the preclinical modeling of human disease, and discover novel targets for RA.Methods:A rat CIA model was performed as previously described.1RNA-Seq was performed on 56 knee synovial tissues collected at multiple time points throughout the course of disease. Differential gene expression was determined at each individual time point and longitudinally with disease progression. Published human synovial datasets were used to categorize these genes into myeloid, lymphoid, fibroid, and low inflammatory signatures.2Differentially expressed genes (DEGs) at each time point were compared to human synovial datasets of RA patients before and after treatment. In addition, we compared disease-driven genes in CIA to genes in RA patients that are unchanged following therapy to identify possible combination therapies.Results:Disease pathology in the rat CIA natural history study progressed as expected: significant decreases were seen in body weight, as well as increases in ankle diameter, paw weight, and histopathology scores of joints in collagen-injected vs noninjected rats. There were 1900 DEGs identified between diseased and naïve rats over the course of disease, representing disease-induced gene signatures (Fig. 1). Comparing these DEGs to reported human RA synovial signatures, both the lymphoid and myeloid signatures were found to be highly upregulated. Interestingly, there were no significant DEGs representing the human fibroid and low inflammatory synovial signatures identified in the CIA rat model. This suggests that the rat CIA model most closely models RA patients with an immune synovial phenotype. In addition, we examined the overlap between disease-driven genes in CIA and genes in RA patients that are unchanged following therapy to identify signaling pathways that may be of utility in combination therapy. Of genes that were upregulated in CIA, 94% of genes that mapped to extracellular matrix-receptor pathways remained unchanged in the synovial tissue of RA patients following tocilizumab treatment.Conclusion:Previous studies have shown that nearly 30% of treatment-naïve early RA patients exhibit a strong fibroid phenotype that correlates with less severe disease and a relatively poor response to disease-modifying anti-rheumatic drugs.3These data indicate that the synovial biology associated with such patients (fibroid or pauci-immune) is not well captured in CIA, the most common preclinical RA model. To assess potential new therapies targeting these patients, it will be necessary to develop alternative animal models with more intact fibroid signatures. In addition to these findings, we also characterized the global molecular changes that occur with disease progression in the CIA rat and made a comparison to RA patients on treatment, providing an overall understanding of disease-relevant pathways in the synovium that may point to possible combination therapies.References:[1]Trentham DE, et al.J Exp Med. 1977;146(3):857-868.[2]Dennis G Jr, et al.Arthritis Res Ther. 2014;16(2):R90.[3]Humby F, et al.Ann Rheum Dis. 2019;78(6):761-772.Disclosure of Interests:Debbie Ruelas Employee of: Gilead, Ruidong Li Employee of: Gilead, Christian Franci Employee of: Gilead, Victor Lira Employee of: Gilead, David Lopez Employee of: Gilead, Li Li Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

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