Peak C-reactive Protein Levels Research Articles

Early Metabolomic and Immunologic Biomarkers as Prognostic Indicators for COVID-19.

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19-89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: -3.30 to -8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.

Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

COVID-19 and myocardial injury: Targeting elevated biomarkers for potential novel therapies

BackgroundThe prevalence of COVID-19 as the primary diagnosis among hospitalized patients with myocardial injury has increased during the pandemic and targeting elevated oxidant stress and inflammatory biomarkers may offer a potential role for novel therapies to improve outcomes. MethodsAt a single VA Medical Center from January 1 through December 31, 2021, troponin assays from patients being evaluated in the Emergency Room for consideration of admission were analyzed and peak levels from each patient were considered abnormal if exceeding the Upper Reference Limit (URL). Among admitted patients with an elevated troponin level, ICD-10 diagnoses were categorized, biomarker elevations were recorded, and independent predictors of death in patients with COVID-19 were determined at a median of 6-months following admission. ResultsOf 998 patients, 399 (40 %) had a negative troponin and were not included in the analysis. Additional patients with an elevated troponin were also excluded, either because they were not admitted (n = 68) or had a final diagnosis of Type 1 MI (n = 117). Of the remaining 414 patients with an elevated peak troponin, COVID-19 was the primary diagnosis in 43 patients (10 %) and was the 4th most common diagnosis of patients admitted with myocardial injury behind congestive heart failure, sepsis, and COPD or pneumonia. At a median of 6-months following admission, 18 (42 %) of the COVID-19 patients had died and independent predictors of death (Odd Ratio: Confidence Intervals) were age (1.18: 1.06‒1.37), Troponin level (Log 10 transformed) (16.54: 2.30‒266.65) and C-Reactive Protein (CRP) (1.30: 1.10‒1.65). ConclusionsNewly diagnosed COVID-19 during the pandemic was a common cause of elevated troponin in hospitalized patients without a Type 1 MI. Age, peak troponin level and peak CRP level were independent predictors of poor outcomes and suggest a need to target these cardiac biomarkers, potentially with novel antioxidant or anti-inflammatory therapies.

D-dimers as a prognostic plasma biomarker in patients with a first episode of acute pericarditis

Abstract Introduction/Background At present the impact of plasma biomarkers in predicting outcome of patients with isolated acute pericarditis (AP) has been poorly investigated. Purpose This study aimed to investigate the prognostic role of fibrin d-dimers (DD), an easily obtainable biomarker, in patients with AP. Methods This is a prospective clinical study enrolling 265 consecutive patients hospitalized between September 2010 and May 2019 with a first episode of AP. At baseline demographics, clinical features, laboratory, imaging findings and treatment were recorded. All patients were followed-up for a minimum period of 18 months. DD measurement at presentation was at the discretion of the examining physician since their measurement is not performed as per protocol in patients with suspected AP. End-points included cardiac tamponade, new-onset atrial fibrillation, pericardial drainage, recurrent/constrictive pericarditis and death. Results DD were measured in 165 out of 265 patients (62.3%, median levels 1456 ng/ml) at presentation. Among them 121 patients (73.3%) presented with elevated age-adjusted DD levels. Patients with elevated DD compared to those without depicted a higher rate of pleural (69.4%, vs 38.6%, p&amp;lt;0.001) and pericardial effusions (89.3% vs 72.7%, p=0.009). Concerning baseline laboratory values, patients with elevated DD presented with lower hematocrit and higher platelet counts, admission and peak C-reactive protein levels, as well as serum Glutamic pyruvic transaminase (SGPT) (Figure 1). In terms of outcome patients with elevated DD depicted a trend towards a greater prevalence of pericardial tamponade vs those without (14.9% vs 4.5% respectively, p=0.07). No significant difference was observed in the remainder of the endpoints during a median follow-up of 51 months. Notably, 43.8% of patients with elevated DD underwent computed tomography pulmonary angiography (CTPA), with all of the examinations being negative for pulmonary embolism. Conclusion Elevated DD plasma values in AP patients is a marker of high inflammatory burden. A trend of this plasma biomarker elevation and in-hospital cardiac tamponade was also observed. DD elevation in AP patients should be interpreted with caution and should not prompt unnecessary investigations (such as CTPA).

Cladribine and Cyclophosphamide Lymphodepletion Prior to Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma

Introduction : Chemotherapy-based lymphodepletion (LD) with fludarabine and cyclophosphamide (Flu/Cy) is a standard preparatory step for chimeric antigen T-cell (CAR T) therapy and its importance for optimal CAR T expansion and efficacy is well-established. An international Flu shortage required our center and others to utilize alternative agents for LD or risk interruption in patient therapy. When unable to utilize Flu as part of the LD regimen for patients with relapsed/refractory large B-cell lymphoma (RR LBCL) that required CD19-directed CAR T as a standard of care therapy, our center adopted a standard operating procedure to substitute Flu with Cladribine (Clad), an alternate purine analogue with similar chemical structure, as part of Clad/Cy LD prior to axicabtagene ciloleucel (axi-cel). Here we report outcomes in these patients. Methods : We performed a retrospective, single-center analysis of consecutive RR LBCL patients who received Clad/Cy LD prior to axi-cel at Moffitt Cancer Center between 8/2022 and 1/2023, and compared outcomes to a historical cohort, consisting of 144 Flu/Cy axi-cel LBCL patients treated between 11/2017 and 2/2021. The Clad/Cy LD regimen, given as standard care, maintained Cy at 500 mg/m 2 and substituted Flu 30 mg/m 2 with Clad 5 mg/m 2/day with both agents given on Days -5, -4, and -3. For efficacy we compared best overall response (BOR) at 90 days and progression-free survival (PFS) comparing the two LD regimens. For safety we compared the rates of cytokine release syndrome (CRS) and neurotoxicity as graded by ASTCT criteria. We also performed correlative analyses exploring absolute lymphocyte count (ALC) kinetics, axi-cel expansion by quantitative PCR, and changes in the cytokine milieu as assessed by the enzyme-linked immunosorbent Ella™ system (Bio-Techne, Oxford, UK) at serial time points following infusion. Results : 23 patients received Clad/Cy LD followed by axi-cel for R/R DLBCL. Baseline characteristics of the study cohort based on LD are shown in the Table. Compared to the historical cohort, Clad/Cy patients received axi-cel after fewer lines of treatment (median 2 [range, 1-3] vs 2 [range, 1-7]; Rank-Sum test p&amp;lt;0.01) and had a greater proportion of relapsed (not refractory) disease (52% vs 22%, p&amp;lt;0.01). The 90-day BOR did not differ between the Clad/Cy and Flu/Cy groups (79% vs 84%; P=0.54) with a similar distribution of complete (22% vs 24%) and partial responders (57% vs 60%). With a median follow-up of 4.6 (95% CI, 3.2-6.2) months for Clad/Cy and 24.2 (95% CI, 21.5-25.8) months for Flu/Cy cohorts, PFS was similar (Figure 1B, Log-Rank p=0.84). Rates of CRS grade ≥ 2 were higher in the Clad/Cy cohort (70% vs 44%; p=0.02), but no CRS grade ≥ 3 was observed in the Clad/Cy compared to 13 (9%) of Flu/Cy patients, including three grade 5 events. Neurotoxicity ≥ grade 2 (44% vs 43%; p=0.77) and peak C-reactive protein levels (15 vs Flu/Cy 12; p=0.3) did not differ for the Clad/Cy and Flu/Cy cohorts. Both regimens had comparable peak axi-cel copy numbers (Clad/Cy 7.9 × 10 6 vs Flu/Cy 5.1 × 10 6 copies/µg). Clad/Cy resulted in a predictable decrease in the ALC from Day -5 to Day 0, but a less profound degree of lymphopenia on Day 0 (0.04 vs 0.02; p&amp;lt;0.01) with ALC 0 achieved later (Day +2 [IQR, +1 to +4] vs Day +1 [IQR, -1 to +2] for Flu/Cy). The median magnitude of change of cytokine levels (Delta = Day -5 - Day 0 concentration) differed between Clad/Cy and Flu/Cy for all tested analytes except IL-6 (3.4 vs 4.6 pg/mL for Flu/Cy; p=0.29). Clad/Cy resulted in greater increases in IL-2 (0.5 vs 0.2 for Flu/Cy; p=0.01) and GM-CSF (2.0 vs 0.9 for Flu/Cy; p=0.03), whereas Flu/Cy had higher IL-15 (31.4 vs 16.8 for Clad/Cy; p&amp;lt;0.01). Interestingly, IFN-γ tended to increase in Clad/Cy and to decrease in Flu/Cy (1.2 vs 0.0; p=0.01). Conclusions : Clad/Cy LD is feasible for axi-cel conditioning in the treatment of RR LBCL. Although it resulted in less profound LD on the day of CAR T infusion, a later ALC nadir, and a different cytokine milieu compared to Flu/Cy, it was associated with similar peak axi-cel expansion and, at short term follow-up, there appears to be similar initial efficacy and toxicity. Future analyses focusing on response durability and long-term toxicities such as infections and post-CAR T cytopenias are warranted.

CT findings of 144 in-hospital patients with influenza pneumonia: A retrospective analysis

Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations. In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores. The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73±6.29 vs 12.49±6.69 vs 18.94±4.57, p<0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02±7.27 vs 8.95±5.99, p<0.05). Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia.

Factors Associated with Increased Risk of Major Cardiovascular Events for Patients Undergoing CAR T Therapy

Introduction: Chimeric antigen receptor (CAR)-T cell therapy use has increased exponentially following its approval for multiple indications in non-Hodgkin lymphomas, multiple myeloma, and acute lymphoblastic leukemia. While cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias are well-described and frequently encountered side effects, a significant proportion of patients experience major adverse cardiovascular events (MACE). This study investigates factors associated with increased risk for MACE. Methods: We performed a retrospective analysis of a consecutive cohort of patients treated with CAR-T therapy at our center between 2018 and 2022. Clinical, laboratory, and imaging parameters were collected. MACE were defined as acute myocardial infarction (AMI), stroke or transient ischemic attack, cardiovascular death, unstable angina, life-threatening arrhythmias, and heart failures. Data was analyzed using SPSS v23. Categorical variables were compared using univariate chi-square test. Results: A total of 126 patients were included. Of these, ten patients (12.5%) had a MACE event. Baseline characteristics including age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, CRS, ICANS, and tocilizumab use are summarized in Table. The median follow-up period was 8.9 months. Patients who experienced MACE versus no MACE had a significantly higher age at CAR-T cell therapy (74.5 years vs. 64.9 years, p = .009), higher peak C-reactive protein (CRP) with a median of 116.7 mg/dL versus 73.85 mg/dL, p = 0.006 respectively. CRS and ICANS grades were associated with MACE events (p = 0.008 and 0.005, respectively). No echocardiographic differences were found. No progression free or overall survival differences were observed in the groups (p = 0.67 and 0.16, respectively). Conclusions: Our results indicate that patients undergoing CAR-T cell therapy who are older and who experience an increased degree of inflammatory response, reflected by peak CRP level, were associated with MACE. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE in CAR-T therapy-treated patients. Prospective inflammation monitoring combined with trials incorporating anti-inflammatory strategies may mitigate the risk of MACE in this patient population. Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. G. Kaur Consultant or advisory role: SANOFI, BMS, Janssen, Cellectar, Arcellx Y. F. Madanat Consultant or advisory role: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Honoraria: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Educational grants: Blueprint Medicines and Morphosys.

Evaluation of neurodevelopmental impairments and risk factors in children following cardiac surgery: The first cohort from China

ObjectiveNeurodevelopmental impairment has been realized as the most common complication in children with congenital heart disease undergoing cardiac surgery during the past 30 years. But little attention has been paid to this problem in China. The potential risk factors for adverse outcomes include demographic, perioperative, and socioeconomic factors, which are vastly different in China compared with the developed countries in previous reports. MethodsFour hundred twenty-six patients (aged 35.9 ± 18.6 months) at about 1- to 3-year follow-up after cardiac surgery were prospectively enrolled from March 2019 to February 2022. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination, and performance skills. Demographic, perioperative, socioeconomic, and feeding type during the first year of life (breastfeeding, mixed, or never breastfeeding) were examined to identify the risk factors for adverse neurodevelopmental outcomes. ResultsMean scores were 90.0 ± 15.5 for development quotient, 92.3 ± 19.4 for locomotor, 89.6 ± 19.2 for personal-social, 85.5 ± 21.7 for language, 90.3 ± 17.2 for eye-hand coordination, and 92 ± 17.1 for performance subscales. For the entire cohort, the impairment in at least 1 subscale was found in 76.1% of the cohort (>1 SD below population mean) with 50.1% being severe (>2 SDs below the mean). The significant risk factors included prolonged hospital stay, peak level of postoperative C-reactive protein, socioeconomic status, and never breastfeeding or mixed feeding. ConclusionsNeurodevelopmental impairment is substantial in terms of incidence and severity in children with congenital heart disease undergoing cardiac surgery in China. Risk factors contributing to the adverse outcomes included prolonged hospital stay, early postoperative inflammatory response, socioeconomic status, and never breastfeeding or mixed feeding. There is an urgent need for standardized follow-up and neurodevelopmental assessment in this special group of children in China.

High pre-transplant Mucosal Associated Invariant T Cell (MAIT) count predicts favorable course of myeloid aplasia.

Mucosal Associated Invariant T (MAIT) cells are unconventional T cells with anti-infective potential. MAIT cells detect and fight against microbes on mucosal surfaces and in peripheral tissues. Previous works suggested that MAIT cells survive exposure to cytotoxic drugs in these locations. We sought to determine if they maintain their anti-infective functions after myeloablative chemotherapy. We correlated the amount of MAIT cells (measured by flow cytometry) in the peripheral blood of 100 adult patients before the start of myeloablative conditioning plus autologous stem cell transplantation with the clinical and laboratory outcomes of aplasia. The amount of MAIT cells negatively correlated with peak C-reactive protein level and the amount of red blood cell transfusion units resulting in earlier discharge of patients with the highest amount of MAIT cells. This work suggests the anti-infectious potential of MAIT cells is maintained during myeloid aplasia.

Association of peak C-reactive protein with long-term clinical outcomes in patients with ST-segment elevation myocardial infarction.

Peak C-reactive protein (CRP) levels following ST-segment elevation myocardial infarction (STEMI) are associated with left ventricular thrombus formation or cardiac rupture. However, the impact of peak CRP on long-term outcomes in patients with STEMI is not completely understood. The purpose of this retrospective study was to compare the long-term all-cause death after STEMI between patients with and without high peak CRP levels. We included 594 patients with STEMI, and divided them into the high CRP group (n = 119) and the low-moderate CRP group (n = 475) according to the quintile of peak CRP levels. The primary endpoint was all-cause death after the discharge of the index admission. The mean peak CRP level was 19.66 ± 5.14mg/dL in the high CRP group, whereas that was 6.43 ± 3.86mg/dL in the low-moderate CRP group (p < 0.001). During the median follow-up duration of 1045days (Q1 284days, Q3 1603days), a total of 45 all-cause deaths were observed. The Kaplan-Meier curves showed that all-cause death was more frequently observed in the high CRP group than in the low-moderate CRP group (p = 0.002). The multivariate Cox hazard analysis revealed that high CRP was significantly associated with all-cause death (hazard ratio 2.325, 95% confidence interval 1.246-4.341, p = 0.008) after controlling for confounding factors. In conclusion, high peak CRP was significantly associated with all-cause death in patients with STEMI. Our results suggest that peak CRP may be useful to stratify patients with STEMI for the risk of future death.

Effectiveness of a postoperative continuous irrigation system via a catheter following implant-based breast reconstruction

Background Implant-based breast reconstruction is a technique frequently used for breast reconstruction. Infection and inflammation are considered to be the most troublesome complications of implant-based breast reconstruction and can lead to capsular contracture or implant failure. To date, however, only a few methods have been proposed to prevent these complications. Therefore, the authors introduce a simple irrigation system using indwelling drain catheters to decrease postoperative inflammation.Methods Continuous saline irrigation was performed once per day for 3 days immediately after prosthesis-based breast reconstruction. Normal saline (500 mL) was inserted into the implant pocket through a superomedial-oriented drain catheter and drained through an inferolateral-oriented drain catheter using a suction device. Inflammatory indicators, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and postoperative complications were compared between the non-irrigation and irrigation groups.Results This study included 37 patients divided into two groups (20 non-irrigation and 17 irrigation). An analysis of inflammatory indicators revealed that the peak CRP level in the irrigation group was significantly lower than that in the non-irrigation group, while no statistically significant differences were found for the other mediators (ESR and WBC). In the immediate postoperative period, continuous irrigation effectively washed out tissue debris and blood clots within the implant pocket, which helped maintain the function of the drain catheter and decrease pro-inflammatory mediators.Conclusions This irrigation method was simple and cost-effective for decreasing inflammation within the breast pocket. Furthermore, it can also be applied to infected breast pockets in combination with antibiotics.

P481 Visceral fat to skeletal muscle area ratio predicts for Ustekinumab loss of response.

Abstract Background Loss of response (LOR) to anti-TNFα therapy in inflammatory bowel disease (IBD) is common and biologic therapies such as anti-IL12/23 agents have shown greater durability in efficacy. Anti-TNFα LOR is increased in higher body mass index (BMI) patients however the evidence for the association between body composition or BMI and Ustekinumab’s (Ust) therapeutic response is limited, with the latter not impacting clinical efficacy in the ‘IM-MUNITI’ post-hoc analyses. This study’s primary aim was to evaluate the impact of body composition on time to LOR to Ustekinumab in Crohn’s disease (CD) patients. Methods 99 adult CD patients aged ≥16 yrs. from two tertiary IBD centres were studied retrospectively. Included patients had received Ust ≥12 weeks, abdominal imaging (CT or MRI) within 6 months of Ust induction, and documented follow up until 30th April 2022. A single experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle (SMA), and subcutaneous fat at the mid L3 vertebral level. Each compartment was corrected for height2 to derive visceral fat (VFI), skeletal muscle (SMI) and subcutaneous fat (SFI) indices. VFA:SMA ratio was also calculated. Clinico-demographic details including therapeutic and surgical history were recorded. Kaplan Meir survival analyses, univariate and multivariate cox regression analyses were performed to evaluate factors predictive of Ust LOR. Results 99 patients met the inclusion criteria with mean age (±SE) 46.6yrs (±1.6) and 49 (49.5%) male. 63 (63.6%) patients were bio-experienced. Univariate Cox regression analyses of age, sex, BMI, peak C-reactive protein (CRP) and nadir Albumin level within 3 months of the CT/MRI scan, disease duration, prior biologic failure and concurrent immunomodulator used within 6 months of Ust induction showed that none of these were predictive of Ust LOR (P&amp;gt;0.05). There was a numerical trend for the middle VFI tertile (40.01-79.99cm2/m2) to having a lower risk for LOR compared to the lowest and highest VFI tertile (Fig. 1a), (HR=0.37, 95%CI= 0.13, 1.11, P=0.08), as well as a higher SMI for having a lower risk of LOR (Fig. 1b), (HR= 0.6, 95%CI= 0.24,1.31, P= 0.18), but these were not statistically significant. A higher VFA: SMA ratio however, was a significant predictor of LOR (HR=2.98, 95%CI 1.2,7.3, P= 0.02) (Fig. 1c), which persisted when it was adjusted on multivariate analysis for age, sex, albumin, CRP, BMI, disease duration, prior biologic failure and concurrent immunomodulator use (HR= 10.6, 95%CI 2.8-39.8, P=&amp;lt;0.0001). Conclusion The ratio of VFA:SMA, but not BMI, is a superior predictor of losing response to Ustekinumab.

Pulmonary function test results and radiological findings 90-120 days after COVID-19 pneumonia: a single-center retrospective study

Background: Survivors of Coronavirus Disease 2019 (COVID-19) pneumonia may have permanent loss of lung function and radiological sequelae. There is a need for markers that predict patients for whom follow-up is required. Aim of the study: To identify the risk factors associated with post-COVID-19 radiological and functional findings. Material and Methods: This is a single-center retrospective study performed in a university hospital. We obtained the data from all hospitalized patients with COVID-19 pneumonia. We included those who underwent pulmonary function tests (PFT) and chest computerized tomography (CT) 90-120 days later. We analyzed initial and peak laboratory results (C-reactive protein (CRP), d-dimer, ferritin, and fibrinogen), and the length of hospital and intensive care unit (ICU) stay. We examined the relationship between baseline data and radiological findings and PFT. Results: Fifty-six patients were included in this study. Of these, 31 (55.4%) were women. The mean age of the patients was 55.05 ± 13.29 years. The mean peak ferritin, fibrinogen, d-dimer, and CRP values recorded during hospitalization follow-up were 285.56 ± 339.82, 518.59 ± 186.93, 1.99 ± 5.69, and 98.94 ± 80.77, respectively. The mean length of hospital and ICU stay were 10.21 ± 8.01 and 8.38 ± 8.90 days, respectively. In 18 (32.1%) patients, we observed a restrictive pattern on PFT, and 22 (39.3%) patients had an abnormal diffusion test. In 21 (37.5%) patients we observed ground glass opacities and in 4 (7.1%) patients reticulation was seen on their chest CT. A multivariate logistic regression analysis revealed that the first visit and peak fibrinogen values were significantly associated with abnormal PFT (p = 0.049, R2 = 0.272), while ferritin and CRP levels at the first visit and peak levels were significantly associated with an abnormality on chest CT (p &lt; 0.001, p = 0.05, respectively). Conclusions: High initial and peak ferritin, fibrinogen, and CRP levels were associated with persistent radiological findings on chest CT and abnormal PFT at 90–120 follow-up after COVID-19 pneumonia.

Abstract 13446: Predicting Cardiovascular Risk and Preempting Major Cardiovascular Events During CAR T Therapy

Chimeric antigen receptor (CAR) T cell therapy is a breakthrough personalized, genetically engineered therapy that has been proven effective for the treatment of refractory multiple myeloma and large B cell lymphoma. However, significant major adverse cardiovascular events (MACE) have been reported with its application. To further investigate associated risk factors for MACE, we performed a retrospective analysis of a cohort of consecutive patients treated with CAR T therapy at our center. Clinical, laboratory and imaging parameters were collected for 48 patients. Of these, 7 patients (14.6%) had a MACE event. Variables analyzed included age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), tocilizumab, among others (Table). Peak C-reactive protein (CRP, median [IQR]) level was 76.00 (73.1) mg/dL in patients without MACE and 121.30 (133.22) mg/dL in patients with MACE, p = 0.028). CRS and ICANS grades were associated with MACE events ( p = 0.039 and 0.03, respectively). No echocardiographic differences were found. Our results indicate that the degree of inflammatory response, reflected by peak CRP level, is associated with MACE events in patients receiving CAR T therapy. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE complications in patients receiving CAR T therapy. Prospective inflammation monitoring and anti-inflammatory strategies may preempt MACE in this patient population.

Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial.

BackgroundIon channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recovery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes.MethodsRECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned.ResultsThe trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52–1.14) with amiodarone and 0.97 (0.81–1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27–2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37–3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying.ConclusionsIn this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.

Postoperative serum C-reactive protein dynamics after pharyngolaryngectomy with jejunal free-flap reconstruction.

Pharyngolaryngectomy with jejunal free-flap (JFF) reconstruction can be offered for locally advanced hypopharyngeal cancer. However, the procedure carries significant morbidity. Postoperative serial serum C-reactive protein (CRP) has been shown to be a marker predicting postoperative complications, and the aim of this study was to describe the dynamics and value of CRP in this patient group. Retrospective analysis of pharyngolaryngectomies with JFF reconstruction was performed in our institution. Daily postoperative CRP values were analysed within the first 14 days, as were complications. Twenty-one cases were included. Total morbidity was 57.1% including 14.3% (temporary) anastomotic leaks and 14.3% flap failures. Patients in the normal group showed peak CRP levels around postoperative day 2 (2.2). Increased CRP levels on or after day 4 were associated with complications (p<0.01) with a sensitivity of 83.3% and specificity of 77.8%. In keeping with CRP kinetics from other surgical studies, peak CRP values on day 2 or 3 are expected, followed by a decline. Peaks in CRP on day 4 or later raise the suspicion of complications. CRP is not specific for any one complication but rather can help guide early appropriate clinical assessment and management. The natural postoperative CRP response peaks around postoperative day 2 (2.2) and declines thereafter. Rising CRP levels after postoperative day 3 are suspicious of surgical complications (p<0.01) with positive and negative predictive values of 83.3% and 77.8%, respectively. Therefore, serial postoperative CRP can be used as an adjunct to monitor outcomes in this group.

LONG -TERM FOLLOW-UP OF COVID-19 PATIENTS TO ASSESS THE RISK FACTORS FOR THE DEVELOPMENT OF POST-COVID FIBROSIS

Purpose: This study aimed to nd the risk factors associated with the development of brosis in follow-up CT in patients of COVID-19 pneumonia. In this retrospective study, fty-four patients with RT-Methods: PCR proved COVID-19 pneumonia with two chest CTs in a 12-month interval between the initial and follow-up CT were included. Patients were classied into two groups: Patients with complete resolution and patients with brosis on follow-up CT. Demographic, laboratory, and therapeutic data and CT ndings were compared and analyzed. A total of 54 patientsResults: (38 men, 16 women) were included in this study. Post-COVID brosis and brotic-like changes were observed on follow-up CT scans in 34 of the 54 patients (63%). The remaining 20 patients (37%) showed no brotic changes with complete resolution. Patients with post covid brosis were signicantly older than those with normal CT. Males were affected more than females. Patients with post covid brosis had more comorbidities when compared with patients without comorbidities. Post-Covid brosis patients had a greater frequency of ICU admission, high frequency noninvasive mechanical ventilation( NIV), higher peak levels of C-reactive protein and D-dimer levels, low level of SpO2, and high CT Severity score in initial CT. Conclusion: Elderly patients, patients with comorbidities, high CT severity score, longer duration of hospital stay, ICU admission, high CRP and D dimer levels, Patients with NIV were associated with more prevalence of brosis in follow up CT.

Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease

ObjectiveTo determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease. Patients and MethodsWe undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT). ResultsAmong 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001). ConclusionInitial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)—Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas–kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed. The primary study outcome was the detection of occurrence of early pancreatic graft dysfunction (ePGD), the secondary study outcome was early renal graft dysfunction (eRGD) as well as all other outcome parameters associated with the graft function. In this context, ePGD was defined as pancreas graft-related complications including graft pancreatitis, pancreatic abscess/peritonitis, delayed graft function, graft thrombosis, bleeding, rejection and the consecutive need for re-laparotomy due to graft-related complications within 3 months. With regard to analyzing ePGD, serum levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), pancreatic lipase as well as neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) were measured preoperatively and at postoperative days (POD) 1, 2, 3 and 5. Further, peak serum levels of CRP and lipase during the first 72 h were evaluated. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for ePGD and eRGD. Cut-off levels were calculated with the Youden index. Significant diagnostic biochemical cut-offs as well as other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 105 patients included, 43 patients (41%) and 28 patients (27%) developed ePGD and eRGD following SPKT, respectively. The mean WBC, PCT, NLR, PLR, CRP and lipase levels were significantly higher on most PODs in the ePGD group compared to the non-ePGD group. ROC analysis indicated that peak lipase (AUC: 0.82) and peak CRP levels (AUC: 0.89) were highly predictive for ePGD after SPKT. The combination of both achieved the highest AUC (0.92; p < 0.01) in predicting ePGD. Concerning eRGD, predictive accuracy of all analyzed serological markers was moderate (all AUC < 0.8). Additionally, multivariable analysis identified previous dialysis/no preemptive transplantation (OR 2.4 (95% CI: 1.41–4.01), p = 0.021), donor age (OR 1.07 (95% CI: 1.03–1.14), p < 0.010), donor body mass index (OR 1.32 (95% CI: 1.01–1.072), p = 0.04), donors cerebrovascular cause of death (OR 7.8 (95% CI: 2.21–26.9), p < 0.010), donor length of ICU stay (OR 1.27 (95% CI: 1.08–1.49), p < 0.010), as well as CIT pancreas (OR 1.07 (95% CI: 1.03–1.14), p < 0.010) as clinical relevant prognostic predictors for ePGD. Further, a peak of lipase (OR 1.04 (95% CI: 1.02–1.07), p < 0.010), peak of CRP levels (OR 1.12 (95% CI: 1.02–1.23), p < 0.010), pancreatic serum lipase concentration on POD 2 > 150 IU/L (OR 2.9 (95% CI: 1.2–7.13), p = 0.021) and CRP levels of ≥ 180 ng/mL on POD 2 (OR 3.6 (95% CI: 1.54–8.34), p < 0.01) and CRP levels > 150 ng/mL on POD 3 (OR 4.5 (95% CI: 1.7–11.4), p < 0.01) were revealed as independent biochemical predictive variables for ePGD after transplantation. Conclusions: In the current study, the combination of peak lipase and CRP levels were highly effective in predicting early pancreatic graft dysfunction development following SPKT. In contrast, for early renal graft dysfunction the predictive value of this parameter was less sensitive. Intensified monitoring of these parameters may be helpful for identifying patients at a higher risk of pancreatic ischemia reperfusion injury and various IRI- associated postoperative complications leading to ePGD and thus deteriorated outcome.