Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

Objective: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. Design: An observational, analytical, retrospective cohort study with longitudinal follow-up. Setting: Hospital Universitario Príncipe de Asturias (HUPA). Participants: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. Main outcome measures: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). Results: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. Conclusions: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient’s inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure.

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Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years)

Cancer Biomarkers ◽

10.3233/cbm-201497 ◽

2020 ◽

pp. 1-10

Author(s):

Maja Sirotković-Skerlev ◽

Natalija Dedić Plavetić ◽

Filip Sedlić ◽

Sanja Kusačić Kuna ◽

Damir Vrbanec ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Serum Levels ◽

High Serum ◽

Clinicopathological Parameters ◽

Enzyme Linked Immunosorbent Assay ◽

Breast Cancer Patients ◽

P53 Antibodies

BACKGROUND: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. OBJECTIVE: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. METHODS: Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. RESULTS: Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. CONCLUSIONS: Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

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Prognostic Value of CA125 Serum Levels in Female Patients with Acute Coronary Syndrome

10.21203/rs.3.rs-395092/v1 ◽

2021 ◽

Author(s):

YanHong Luo ◽

YongRan Cheng ◽

XiaoFu Zhang ◽

MingWei Wang ◽

Bin Ni ◽

...

Keyword(s):

Heart Failure ◽

Acute Coronary Syndrome ◽

Prognostic Value ◽

Serum Levels ◽

Left Ventricular ◽

Short Term ◽

Female Patients ◽

Coronary Syndrome ◽

Ca125 Level

Abstract Background: carbohydrate antigen 125 (CA125) is an increasingly promising biomarker of heart failure (HF), but its prognostic value in female patients with acute coronary syndrome (ACS) is unclear. We aimed to determine the short-term and mid-term prognostic value of CA125 serum levels in female ACS patients.Methods: A total of 131 consecutive female patients with ACS were retrospective enrolled. Their CA125 levels, B-type natriuretic peptide (BNP) levels and biochemical parameters were measured, and echocardiography was performed at admission. All-cause mortality during hospitalization and two-year follow-up was investigated for the prognosis.Results: The median value of CA125 serum level in the entire ACS patients was 13.85 U/mL. Patients in Killip Ⅲ had the highest values of CA125 level, followed by Killip Ⅱ and then Killip Ⅰ (p < 0.05). However, no statical difference was observed between Killip Ⅳ and Ⅰ-Ⅲ groups respectively (P > 0.05). The CA125 serum levels showed weak positive correlation with left ventricular end-diastolic diameter (LVEDD) (r = 0.3, P < 0.01) and a weak negative correlation with left ventricular ejection fraction (LVEF) (r = –0.23, p < 0.01). A receive operating characteristic (ROC) curve analysis showed that the AUC of CA125 in predicting acute heart failure (AHF) in ACS patients during hospitalization was 0.912, exhibiting higher sensitivity and specificity than BNP (0.846). The optimal cut-off value for CA125 in predicting AHF was 16.4 U/mL with a sensitivity of 0.916 and specificity of 0.893. The Kaplan-Meier survival analysis demonstrated that patients with high values of CA125 level had a poor overall survival than those with low values of CA125 level (log-rank, p < 0.001), whether during hospitalization or mid-term follow-up. Conclusion: Elevated CA125 level can be used to predict AHF in female ACS patients. Patients with elevated CA125 levels had higher mortality in short-term and mid-term than those with low CA125 levels.

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Changes and evolution among SARS-COV-2 hospitalised patients in terms of severity, mortality and virus genome in a Spanish cohort

10.21203/rs.3.rs-199395/v1 ◽

2021 ◽

Author(s):

Rocío Aznar-Gimeno ◽

J. Ramón Paño-Pardo ◽

Luis M. Esteban ◽

Gorka Labata-Lezaun ◽

M. José Esquillor-R ◽

...

Keyword(s):

Risk Factors ◽

Retrospective Cohort ◽

Mortality Rates ◽

Virus Genome ◽

Hospitalized Patients ◽

Icu Admission ◽

Hospitalised Patients ◽

Survival Differences ◽

Second Wave ◽

Spanish Cohort

Abstract A comparison between pandemic waves could help to understand the evolution of this disease. The objective of this work was to study the evolution of COVID-19 hospitalized patients on different pandemic waves in terms of severity and mortality. We performed an observational retrospective cohort study of hospitalized patients (5,220) with SARS-CoV-2 infection from February to September in Aragon, Spain. In a comparative way, we analyzed ICU admission and 30-day mortality, clinical characteristics and risk factors, of first and second waves. SARS-CoV-2 virus genome were analyzed in 236 samples. Patients in the first wave (n=2,547) were older (74 y, IQR: 60-86 vs. 70 y, IQR: 53-85; p<0.001) and showed worse clinical and analytical parameters related to severe COVID-19 than in the second wave (n=2,673). The probability of ICU admission at 30 days was 16% and 10% in the first and second wave, respectively (p<0.001). The cumulative 30-day mortality rates were 38% in the first wave and 32% in the second one (p=0.007). Survival differences were observed among patients aged 60 to 80 years. There was variability among death risk factors and virus genome between waves. Therefore, the two COVID-19 pandemic waves analyzed were different, in terms of disease severity and mortality.

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Increased Risk of Velopharyngeal Insufficiency in Patients Undergoing Staged Palate Repair

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665620913440 ◽

2020 ◽

Vol 57 (8) ◽

pp. 975-983

Author(s):

Hilary McCrary ◽

Sarah Hatch Pollard ◽

Vanessa Torrecillas ◽

Leon Khong ◽

Helene M. Taylor ◽

...

Keyword(s):

Cleft Palate ◽

Retrospective Cohort ◽

Outcome Measure ◽

Single Stage ◽

Velopharyngeal Insufficiency ◽

Increased Risk ◽

Management Procedures ◽

Palate Repair ◽

Surgery Rates

Objective: To evaluate the association of 2-stage cleft palate (CP) surgery on velopharyngeal insufficiency (VPI) incidence, speech surgeries, and cleft-related surgical burden. Design: Retrospective cohort with follow-up of 4 to 19 years. Setting: Academic, tertiary children’s hospital. Patients: Patients who underwent CP surgery between 2000 and 2017. Exclusions included submucous CP or age at last contact under 3.9. Interventions: Cleft palate surgery, completed in either a single-stage or 2-stage repair. Main Outcome Measure(s): Rates of VPI diagnosis and speech surgery and total cleft surgeries; t tests, tests of proportion, and linear and logistic regression were performed. Total cleft-related surgeries were examined in a subset (n = 418) of patients with chart reviews. Results: A total of 1047 patients were included; 59.6% had 2-stage CP repair, 40.4% had single-stage repair. Approximately 32% of children with 2-stage CP repair were diagnosed with VPI, as opposed to 22% of single-stage patients ( P < .001). Children with 2-stage CP repair were 1.8 times as likely to be diagnosed with VPI ( P < .001). Speech surgery rates were similar across groups. Patients who had 2-stage repair received an average of 2.3 more cleft-related procedures, when excluding prosthesis management procedures. Conclusion: Our data show an increased risk of VPI diagnosis and increased surgical burden among patients receiving 2-stage CP repair.

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Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique—A Pilot Study

Journal of Clinical Medicine ◽

10.3390/jcm10040776 ◽

2021 ◽

Vol 10 (4) ◽

pp. 776

Author(s):

Michael C. Tanner ◽

Sonja Boxriker ◽

Patrick Haubruck ◽

Christopher Child ◽

Fabian Westhauser ◽

...

Keyword(s):

Growth Factors ◽

Treatment Protocol ◽

Blood Perfusion ◽

Serum Levels ◽

Non Union ◽

Masquelet Technique ◽

Before And After ◽

Diamond Concept ◽

Lost To Follow Up

Two-step Masquelet-technique established a new procedure in the treatment of osseous defects, addressing prerequisites postulated by the “diamond concept”. Increase in blood perfusion and growth factors are enhanced by the “Masquelet-membrane”. To describe this, we measured serum levels of Vascular Endothelial Growth Factor (VEGF) of patients with atrophic non-unions of long bones undergoing Masquelet-technique. From over 500 non-union patients undergoing Masquelet-technique with prospective follow-up we randomly selected 30 patients. 23 were included, 7 lost to follow-up or excluded because of incomplete data. Serum was drawn at specified intervals before and after surgery. Patients were followed for at least 6 months after step 2. Classification into both groups was performed according to radiological results and clinical outcome 6 months after step 2. Concentration of VEGF in patients’ serum was performed via ELISA. 14 achieved osseous consolidation (responder group), 9 cases did not (non-responder). Responders showed a significant increase of serum-VEGF in the first and second week when compared to the preoperative values of step 1. Non-responders showed a significant increase of VEGF in the second week after Steps 1 and 2. Comparison of groups showed significantly higher increase of serum-VEGF week2 after step 1 and preoperative to step 2 for responders. Results show one possibility of illustrating therapeutic progress by monitoring growth factors and possibly allowing prognostic conclusions thereof. This might lead to a more targeted treatment protocol.

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The Prognostic Value of Retroperitoneal Lymphadenectomy in Apparent Stage IA Endometrial Endometrioid Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.618499 ◽

2021 ◽

Vol 10 ◽

Author(s):

Zhao Liu ◽

Jinghe Lang ◽

Ming Wu ◽

Lei Li

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Lymph Nodes ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Prognostic Value ◽

Lower Uterine Segment ◽

Survival Outcomes ◽

Stage Ia

Study designRetrospective cohort study.IntroductionDebates remain regarding the role of lymphadenectomy in patients with apparent stage IA endometrial cancer, especially subtypes with a favorable prognosis. This study aimed to explore the prognostic value of staging surgeries in apparent stage IA endometrial endometrioid cancer patients in a retrospective cohort study.MethodsCases from June 1, 2010 to June 1, 2017 were reviewed in patients with pathologically confirmed endometrial endometrioid carcinoma limited to <1/2 of the myometrium, without extrauterine metastasis on preoperative evaluation and during surgical inspection. Survival outcomes were compared between patients with and without lymphadenectomy and between patients with and without metastasis to lymph nodes.ResultsIn total, 1,312 eligible patients were included, among which 836 underwent staging surgeries and 476 underwent simple hysterectomy. Twenty-eight patients were found with metastasis to retroperitoneal lymph nodes. After a median follow-up of 57.4 months, lost to follow-up, recurrence, death, and cancer-specific death occurred in 28, 39, 24, and 16 patients, respectively. In a univariate analysis, lymphadenectomy of the pelvis with or without para-aortic lymph nodes had no significant impact on disease-free survival, overall survival or cancer-specific overall survival (p values >0.05). However, after adjusting for important baseline risk factors [menopausal status, tumor differentiation, maximum diameter and location, lymph-vascular space invasion (LVSI) status, and postoperative adjuvant therapy), lymphadenectomy resulted in significantly improved survival outcomes (p values <0.05). Menopause (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.3–16.4, p=0.015), tumor diameter larger than 2 cm (OR 4.6, 95% CI 1.3–16.0, p=0.016), grade 3 tumors (OR 3.0, 95% CI 1.0–8.5, p=0.042), positive LVSI (OR 8.7, 95% CI 3.7–20.4, p<0.001) and lower uterine segment involvement (OR 3.1, 95% CI 1.4–7.2, p=0.007) had more extrauterine metastases.ConclusionIn cases of apparent stage IA endometrioid endometrial carcinoma, staging surgeries should be considered in patients with larger, higher grade tumors, positive LVSI, or lower uterine segment involvement.

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Prognostic Significance of the Fission1/Parkin Ratio for Sepsis: A Prospective Cohort Study

Frontiers in Medicine ◽

10.3389/fmed.2021.642749 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wei Huang ◽

Xiaoting Wang ◽

Hongmin Zhang ◽

Guangjian Wang ◽

Dawei Liu

Keyword(s):

Operating Characteristic ◽

Independent Predictor ◽

Mitochondrial Fission ◽

Prognostic Significance ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Icu Admission

Introduction: Fission1 (Fis1) and parkin are key proteins related to mitochondrial fission and mitophagy, respectively. This study aimed to assess the prognostic value of the Fis1/parkin ratio as a biomarker in patients with sepsis.Methods: Consecutive patients with sepsis (n = 133) or simple infection (n = 24) were enrolled within 24 h of arrival at the intensive care unit (ICU). Serum levels of Fis1, parkin, mitofusin2 (Mfn2), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were measured by enzyme-linked immunosorbent assay (ELISA) upon ICU admission. Clinical parameters and standard laboratory test data were also collected. All patients received follow-up for at least 28 days.Results: Patients with sepsis presented with significantly decreased serum levels of parkin, Mfn2, and PGC-1α, but an increased serum Fis1 level and Fis1/parkin, Fis1/Mfn2, and Fis1/PGC-1α ratios at ICU admission. Relative to patients with simple infections, the ratios were remarkably elevated in septic patients—particularly septic shock patients. The area under the receiver operating characteristic (ROC) curve of the Fis1/parkin ratio was greater than that of Fis1, parkin, Mfn2, and PGC-1α levels as well as that of the Fis1/Mfn2 and Fis1/PGC-1α ratios for prediction of 28-day mortality due to sepsis. All of the ratios were significantly higher in non-survivors than survivors at the 28-day follow-up examination. Fis1/parkin ratio was found to be an independent predictor of 28-day mortality in patients with sepsis.Conclusions: The Fis1/parkin ratio is valuable for risk stratification in patients with sepsis and is associated with poor clinical outcomes for sepsis in the ICU.

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Alterations Of The Chemokine Microenvironment In Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.1619.1619 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1619-1619

Author(s):

TILL M SEILER ◽

Roland Aydin ◽

Tobias Herold ◽

Stefan Holdenrieder ◽

Michael Hallek ◽

...

Keyword(s):

T Cells ◽

Growth Factors ◽

Chronic Lymphocytic Leukemia ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

Advanced Stage ◽

Healthy Individuals ◽

T Cell Migration ◽

Cytokines And Chemokines ◽

Disease Specific

Abstract Background In chronic lymphocytic leukemia (CLL), proliferation of the leukemic cell clone occurs in the bone marrow and lymphatic tissues rather than peripheral blood. In this microenvironment, CLL cells interact with accessory cells, such as T-cells and CD68+ nurselike cells (NLCs). In addition, cytokines and chemokines secreted by leukemic cells, stromal cells and T-cells are essential in forming the disease-specific microenvironment. However, the exact biological role of cytokines and chemokines needs to be defined. Methods In order to address this issue, we measured serum levels of 20 chemokines and cytokines in a prospective cohort of 159 previously untreated Binet stage A patients (pts) (GCLLSG CLL1 trial), 50 pts with advanced CLL in need of first line treatment (GCLLSG CLL8 trial) and 27 healthy individuals. For the study cohorts, serum samples had been centrally collected at study entry and stored at -80°C. Sera were analyzed on a Luminex-based multiplex platform, allowing simultaneous screening of multiple serum parameters. Results Serum levels of 13 chemokines (EGF, MCP-1, MIP-1alpha, MIP-1beta, sIl2Ralpha, VEGF, MCP-2, MCP-4, SDF-1, 6CKine, CTACK, TRAIL, SCF) differed significantly between healthy controls and CLL patients (p<0.05), indicating that the expression of these cytokines may potentially impact pathways common to CLL and the disease specific microenvironment. In addition, 7 chemokine serum levels were significantly higher in advanced stage CLL compared to patients at primary diagnosis, indicating a pronounced shift of the chemokine homeostasis upon disease progression. (Table) We identified a strong correlation of inflammatory cytokines (TRAIL, TNFalpha; p=0.039), growth factors (EGF, VEGF, TPO, SCF; p<0.001) and chemokines involved in B- and T-cell migration and homing (MIP-1alpha, MIP-1beta, 6CKine, Il-16; p<0.05). These coordinately regulated cytokines may reflect pathways important to the pathobiology of CLL. Hierarchical cluster analyses revealed distinct chemokine expression patterns in healthy individuals, early CLL and advanced stage disease. Finally, sIl2Ralpha has been previously confirmed as an independent prognostic factor in early stage CLL Conclusion Due to the comparison of 27 healthy individuals and 209 CLL pts we were able to demonstrate that the chemokine homeostasis is significantly altered in CLL compared to healthy individuals. Chemokines involved in B- and T-cell migration and homing and recruitment, inflammation and growth factors are coordinately overexpressed, pointing towards pathways crucial to the formation of a disease specific microenvironment. These pathways might serve as potential targets for future therapeutic strategies. Disclosures: No relevant conflicts of interest to declare.

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AB0666 PROGNOSTIC VALUE OF SERUM KREBS VON DEN LUNGEN-6 GLYCOPROTEIN CIRCULATING LEVELS IN COVID-19 PNEUMONIA: A PROSPECTIVE COHORT STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1359 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1365.1-1365

Author(s):

D. Lobo Prat ◽

I. Castellví ◽

D. Castillo ◽

S. Orozco ◽

A. Mariscal ◽

...

Keyword(s):

Cohort Study ◽

Retrospective Cohort ◽

Prognostic Value ◽

Screening Tool ◽

Clinical Course ◽

Meta Analysis ◽

Area Under The Curve ◽

Serum Levels ◽

Descriptive Study ◽

Circulating Levels

Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; p<0.02).Conclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

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