Elevated Ferritin Levels Research Articles

Predictors of mortality for patients with COVID-19 and large vessel occlusion.

BackgroundThis study evaluates the mortality risk of patients with emergent large vessel occlusion (ELVO) and COVID-19 during the pandemic.MethodsWe performed a retrospective cohort study of two cohorts of consecutive patients with ELVO admitted to a quaternary hospital from March 1 to April 17, 2020. We abstracted data from electronic health records on baseline, biomarker profiles, key time points, quality measures and radiographic data.ResultsOf 179 patients admitted with ischemic stroke, 36 had ELVO. Patients with COVID-19 and ELVO had a higher risk of mortality during the pandemic versus patients without COVID-19 (OR 16.63, p = 0.004). An age-based sub-analysis showed in-hospital mortality in 60% of COVID-19 positive patients between 61-70 years-old, 66.7% in between 51-60 years-old, 50% in between 41-50 years-old and 33.3% in between 31-40 years old. Patients that presented with pulmonary symptoms at time of stroke presentation had 71.4% mortality rate. 27.3% of COVID-19 patients presenting with ELVO had a good outcome at discharge (mRS 0-2). Patients with a history of cigarette smoking (p = 0.003), elevated d-dimer (p = 0.007), failure to recanalize (p = 0.007), and elevated ferritin levels (p = 0.006) had an increased risk of mortality.ConclusionPatients with COVID-19 and ELVO had a significantly higher risk for mortality compared to COVID-19 negative patients with ELVO. A small percentage of COVID-19 ELVO patients had good outcomes. Age greater than 60 and pulmonary symptoms at presentation have higher risk for mortality. Other risk factors for mortality were a history of cigarette smoking, elevated, failure to recanalize, elevated d-dimer and ferritin levels.

Ferritin levels in patients with COVID-19: A poor predictor of mortality and hemophagocytic lymphohistiocytosis.

IntroductionA hyperinflammatory environment has been a hallmark of COVID‐19 infection and is thought to be a key mediator of morbidity. Elevated ferritin has been observed in many patients with COVID‐19. Several retrospective studies have shown ferritin levels can be correlated and predictive of poor outcomes in COVID‐19, though a rigorous analysis has been lacking.MethodsA retrospective analysis of 942 adult COVID‐19 patients admitted in March 2020 at a large New York City health system with available ferritin levels.ResultsThe primary outcome, all‐cause mortality, was observed in 265 (28.1%) patients. Patients who died had a significantly higher median admission and maximum ferritin levels than those who did not. However, death was poorly predicted by admission and maximum ferritin levels on receiver operator curve (ROC) analysis, with AUCs of 0.677 and 0.638, respectively. AUCs increased when the cohort was limited to progressively younger patients. Ferritin levels were minimally better at predicting our secondary outcomes. These included mechanical ventilation, observed in 280 (29.7%) patients with an ROC yielding an area under the curve (AUC) of 0.769, and new renal replacement therapy, observed in 80 (8.5%) of patients with an ROC yielding an AUC of 0.787. We also performed a subset analysis on 22 patients with ferritins >20 000 ng/mL. None of the patients met HLH‐2004 diagnostic criteria. Fifteen (68.2%) of these patients had suspected or confirmed bacterial infections.ConclusionsThough many patients with COVID‐19 present with hyperferritinemia, elevated ferritin levels are not accurate predictors of outcomes and do not appear to be indicative of hemophagocytic lymphohistiocytosis.

Iron overload associated symptoms and laboratory changes in the Swiss Haemochromatosis Cohort - when a clinician should become attentive.

Hereditary haemochromatosis is a genetic disease characterised by progressive accumulation of iron in organs leading to many unspecific complaints, but even today diagnosis may be delayed. We aimed to identify symptoms associated with iron overload and parameters typical in patients with hereditary haemochromatosis which might help to facilitate detection and diagnosis in daily clinical routine. We analysed the prospective Swiss Haemochromatosis Cohort (SHC), including 163 patients for whom serum ferritin levels at diagnosis were available. The cohort was stratified according to the degree of iron overload. Substantial iron overload was defined as serum ferritin concentrations ≥1000 µg/ml. Patients with substantial iron overload had significantly higher liver enzymes (p <0.001) and more often arthropathy of the metacarpophalangeal joints (p <0.001) and upper ankle joint (p = 0.003). Elevated liver enzymes, especially elevated alanine aminotransferase (ALT) levels, were associated with a 10.1-fold (95% confidence interval [CI] 4.8–21.2) increased the risk for serum ferritin levels ≥1000 µg/ml. Furthermore, metacarpophalangeal joint arthropathy emerged as an important predictor for iron overload with a 3.6-fold increased risk (95% CI 1.8–7.1; p <0.001). Only elevated ALT levels and metacarpophalangeal joint arthropathy remained significantly associated with elevated iron levels after adjustment for possible confounders in patients diagnosed with hereditary haemochromatosis. Elevated ALT levels and metacarpophalangeal arthropathy remained independently associated with elevated ferritin levels in patients with haemochromatosis and should prompt clinicians to consider iron overload in patients with hereditary haemochromatosis.   &nbsp.

Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report

BackgroundThe rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse.Case presentationWe report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded.ConclusionCOVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.

Population-based study of serum ferritin in early pregnancy and adverse perinatal outcomes.

Chronic placental inflammation is associated with preterm birth (PTB) and perinatal mortality. Ferritin is often elevated in chronic inflammatory conditions, but prior studies of its relation to PTB were restricted to ferritin measurement within pregnancy, were underpowered to detect rarer outcomes, and did not account for pre-existing maternal inflammatory conditions, such as inflammatory bowel or rheumatological disease. To evaluate whether an elevated ferritin level prior to pregnancy is associated with major adverse pregnancy outcomes. A population-based cohort study was completed using Ontario, Canada. Included were all Ontarian women with a hospital livebirth or stillbirth at ≥20weeks' gestation, 2007-2018, and serum haemoglobin and ferritin measured as an outpatient within 120days before conception. Excluded were women with a diagnosed iron overload disorder or a ferritin concentration <15µg/L. The main exposure was a pre-pregnancy serum ferritin ≥95th percentile. Study outcomes included PTB<37weeks' gestation, including clinician-initiated and spontaneous PTB; PTB<32weeks; chorioamnionitis; and perinatal death. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each study outcome, comparing a serum ferritin concentration ≥95th vs <5th percentile (the referent), while adjusting maternal age, residence, haemoglobin concentration, diabetes mellitus, inflammatory bowel disease, illicit drug/tobacco use, chronic kidney disease, chronic hypertension, sickle-cell disease or thalassaemia, and rheumatological conditions. Among 89847 births, a preconceptional maternal serum ferritin ≥95th (112.0μg/L) vs <5th (16.9μg/L) percentile was associated with an adjusted relative risk (aRR) of 1.34 (95% CI 1.15, 1.57) for PTB, including spontaneous and clinician-initiated PTB. Results were equivocal for chorioamnionitis (aRR 1.23, 95% CI 0.81, 1.86), and there was no association with perinatal mortality (aRR 0.94, 95% CI 0.55, 1.61). A high preconceptional ferritin concentration is associated with some adverse perinatal outcomes.

P1361IS THE INFLAMMATORY STATE A DETERMINING FACTOR OF THE PRIMARY PERMEABILITY OF ARTERIOVENOUS FISTULES?

Abstract Background and Aims Clinical practice guidelines recommend an arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis and are associated with a lower incidence of morbidity and mortality. However, primary vascular access (AV) failure is not uncommon. Low-grade inflammation is present in ERCT. We identify the inflammatory parameters that influence the primary permeability of vascular access for hemodialysis. Method Cross-sectional study; We include all the AVs performed in the HGUCR. We evaluate the initial operation after the creation of the AV. Demographic variables (age, sex), aetiology of CKD and associated comorbidity were collected. Statistical analysis with SPSS 25.0. Categorical variables are expressed as percentages and are compared using the Chi2 Test. Quantitative variables are expressed as mean ± standard deviation and the t-student was used to compare them. We performed a multivariate analysis to determine those factors involved in the primary failure of the VA. Statistical significance for a value of p &amp;lt;0.05. Results 600 VA performed on 466 patients were reviewed between October 2009 and December 2019. 492 autologous VA (86.8%) and 75 prosthetic VA (13.2%) were performed. The mean age of the patients was 65.3 ± 14.2 years and 66.2% were male. The most frequent etiology of CKD was diabetic nephropathy (29.9%), followed by non-affiliated (18%) and glomerulonephritis (16.5%). 90.8% of the patients had arterial hypertension (HT), diabetes mellitus (DM) 48%. 77.2% of AV presented primary permeability. In the univariate analysis using Chi2 and T student, statistical age (p = 0.017), HT (p = 0.002), statin treatment (p = 0.002), antiplatelet therapy (p = 0.001), low ferritin levels (p = 0.011) and PCR (p = 0.019). When performing a multivariate analysis, the high CRP figures (OR: 0.64 95% CI 0.42-0.98 p = 0.043) and ferritinemia (OR: 1.04 95% CI 1.01-1.06 p = 0.013) are predictive factors of primary AV failure. Conclusion In our study, high CRP decreases the probability of primary functioning of AVFs by 36% and elevated ferritin levels are predictors of primary failure after adjusting for age and sex in the multivariate model.

Serum hepcidin levels are related to serum markers for iron metabolism and fibrosis stage in patients with chronic hepatitis B: A cross-sectional study

Background and study aimsThe clinical significance of serum parameters of iron metabolism and hepcidin in liver disease remains unknown. Therefore, this study aimed to evaluate the association of serum hepcidin levels with fibrosis stage and serum iron parameters in patients with chronic hepatitis B (CHB). Patients and MethodsThis cross-sectional study included 126 treatment-naïve patients with CHB (median age, 39.0 years; 64.3% males) who were positive for hepatitis B surface antigen and 23 healthy controls (median age, 33.0 years; 52.2% males). Data on patient demographics, serum hepcidin levels, liver function tests and serum iron parameters and liver biopsy findings including fibrosis grade, histological activity index (HAI) and liver iron level were recorded. ResultsThe median (minimum–maximum) serum hepcidin levels were significantly lower in the CHB group than in the control group [71.2 (13.3–672.7) vs. 657.5 (201.7–2714.2) pg/mL, p < 0.001]. Higher fibrosis stage was associated with higher transferrin saturation (p = 0.029), serum ferritin level (p < 0.001) and viral load (p < 0.001). Fibrosis stage and HAI were positively correlated with ferritin (r = 0.407, p < 0.001 and r = 0.415, p < 0.001, respectively) and transferrin saturation (r = 0.219, p = 0.026 and r = 0.290, p = 0.003, respectively) levels, whereas hepcidin level was negatively correlated with fibrosis stage (r = −0.175, p = 0.051), viral load (r = −0.209, p = 0.020) and ferritin level (r = −0.244, p = 0.006) level. There were no significant differences in serum iron level, total iron binding capacity and liver iron level among patients with different stages of fibrosis. ConclusionReduced hepcidin levels and elevated transferrin saturation and ferritin levels are linked to fibrosis severity and HAI in patients with CHB.

Hubungan antara Kadar Feritin dengan Malondialdehyde pada Pasien Talasemia β Mayor di RSD dr. Soebandi Jember

Repeated blood transfusions, increased iron absorption, and ineffective erythropoiesis in major β thalassemia patients lead to iron overload characterized by elevated ferritin levels. Free iron will catalyze reactive oxygen species (ROS) formation by Fenton reaction that cause oxidative stress. Malondialdehyde (MDA) is the lipid peroxidation end product used to measure the oxidative stress. This study aimed to determine the correlation between ferritin levels and MDA levels in major β thalassemia patients at dr. Soebandi Hospital Jember. An analitic observational study with cross sectional study design which the subjects were 15 patients with major β thalassemia in the Pediatric Department at dr. Soebandi Hospital Jember who met inclusion and exclusion criteria. Ferritin levels measured by Enzyme-Linked Fluorescent Immuno Assay (ELFA) method and MDA levels measured by Thiobarbituric Acid Reactive Substances (TBARS) method using spectrophotometer at 535 nm. Data was analyzed with Shapiro Wilk normality test and Pearson correlation test. The mean of ferritin levels was 3540,46±3925,37 ng/mL and MDA levels was 4,77±2,03 nmol/mL. The result showed that there is strong positive correlation between ferritin levels and MDA levels with p value=0,001 and r=0,786 in major β thalassemia patients at dr. Soebandi Hospital Jember.

COVID-19. Etiology, pathogenesis, diagnosis and treatment

COVID-19 is a new epidemic infectious disease characterized by a relatively high contagiousness and the likelihood of life-threatening complications in the form of acute respiratory distress syndrome (ARDS), acute respiratory and multiple organ failure. The causative agent of the disease is the enveloped zoonotic RNA virus SARS-CoV-2 belongs to the Coronaviridae family, the genus Betacoronavirus, as well as the previously known SARS-CoV and MERS-CoV viruses, which cause severe acute respiratory syndrome and the Middle East respiratory syndrome, respectively. The virus is transmitted by air and contact routes, therefore, to protect medical personnel it is necessary to use individual protective suits and accessories, with protection of the respiratory tract and eyes, disinfection of hands and surfaces as when working with microorganisms of the I-II pathogenicity group. The diagnosis of COVID-19 is confirmed using real-time RT-PCR diagnostics that detect the presence of viral RNA. The clinical manifestations of COVID-19 vary from mild to moderate, to severe and extremely severe (5% of cases, ARDS, multiple organ failure, mechanical ventilation and resuscitation are necessary). The clinical picture of acute respiratory viral infections with severe fever, dry cough, respiratory failure, against the background of lymph and thrombocytopenia, normal procalcitonin, elevated levels of ferritin and CRP in the blood with signs of bilateral, polysegmental pneumonia and the phenomenon of "frosted glass" on CT, even in the absence of an unfavorable epidemiological An anamnesis makes it possible to diagnose COVID-19 with a high degree of probability and hospitalize the patient in an infectious isolation ward, without waiting for the results of PCR diagnostics. There is no specific etioptropic therapy for COVID-19; the only method that has proven effective in limited clinical trials is plasma infusion of convalescents with a high titer of neutralizing antibodies. High hopes are pinned on innovative treatments, such as the creation of neutralizing monoclonal antibodies and cell therapy using MSCs or NK cells. The first SARS-CoV-2 vaccine, mRNA-1273, is currently undergoing clinical trials.

Decreased lung function is associated with elevated ferritin but not iron or transferrin saturation in 42,927 healthy Korean men: A cross-sectional study.

Though elevated ferritin level and decreased lung function both predispose people to cardio-metabolic disease, few reports have investigated the association between them. Furthermore, it remains unclear whether the association reflects a change in iron stores or an epiphenomenon reflecting metabolic stress. Therefore, we looked for possible associations between ferritin, iron, and transferrin saturation (TSAT) and lung function to clarify the role of iron-related parameters in healthy men. We conducted a cohort study of 42,927 healthy Korean men (mean age: 38.6 years). Percent predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) were categorized into quartiles. Adjusted odds ratios (aORs) and 95% confidence intervals (using the highest quartile as reference) were calculated for hyperferritinemia, high iron, and high TSAT after controlling for potential confounders. The median ferritin level was 199.8 (141.5-275.6) ng/mL. The prevalence of hyperferritinemia (defined as >300 ng/mL) was 19.3%. Subjects with hyperferritinemia had lower FEV1% and FVC% than those with normal ferritin level with a slight difference, but those were statistically significant (99.22% vs.99.61% for FEV1%, p = 0.015 and 98.43% vs. 98.87% for FVC, p = 0.001). However, FEV1/FVC ratio was not significantly different between groups (P = 0.797). Compared with the highest quartile, the aORs for hyperferritinemia across decreasing quartiles were 1.081 (1.005-1.163), 1.100 (1.007-1.200), and 1.140 (1.053-1.233) for FEV1% (p for trend = 0.007) and 1.094 (1.018-1.176), 1.101 (1.021-1.188), and 1.150 (1.056-1.252) for FVC% (p for trend = 0.001). However, neither FEV1% nor FVC% was associated with iron or TSAT. Hyperferritinemia was associated with decreased lung function in healthy Korean men, but iron and TSAT were not. Longitudinal follow-up studies are required to validate our findings.

Corona Virus Disease 2019 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition.

ABSTRACTIntroduction:With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19.Methods:An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members.Results:Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD. Among the Porto group members, face-to-face appointments were often replaced by remote consultations but almost all did not change current IBD treatment. Ten guidance points for clinicians caring for PIBD patients in epidemic areas have been endorsed with consensus rate of 92% to 100%.Conclusions:Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other.Supplemental digital content:An infographic accompanying this article can be found at.

Iron metabolism and indicators reflecting its changes in pulmonary tuberculosis (literature review).

Iron is an essential element for human and bacteria, including mycobacterium tuberculosis. Over review includesthe literature on the problem of iron metabolism in patients with tuberculosis and with comorbid pathology HIV infection and tuberculosis. The literature was searched for when writing this review using the RSCI, CyberLeninka, Scopus, Web of Science, MedLine, PubMed databases using the following keywords: iron, ferritin, hepsidin, lactoferrin, tuberculosis, pneumonia, HIV infection. Iron compounds are involved in many redox reactions: oxygen transport, cellular respiration, the trichloroacetic acid cycle, DNA biosynthesis, and others. The ratio of intracellular and extracellular iron in the body is regulated by the low molecular weight hormone hepcidin, the mechanism of action of which is to block the function of ferroportin, an exporter of iron from cells, which leads to the accumulation of the intracellular iron pool and the prevention of the toxic effect of free iron. The role of iron in the interaction of the human body with ferro-dependent bacteria has been established. Iron is necessary for the growth and development of bacterial cells, and the methods for its production from the host are different. Information on the effect of iron metabolism on pulmonary tuberculosis is scarce and contradictory: some authors have identified a decrease in hemoglobin and transferrin in combination with elevated levels of ferritin in patients with tuberculosis; according to other sources, hyperferritinemia in tuberculosis cannot be predictive, but is a marker inflammation. At the same time, there are studies that indicate a significant increase in ferritin in patients with disseminated tuberculosis relative to other clinical forms. Currently, the incidence of tuberculosis in patients with HIV infection is increasing, while diagnostic tests are not very informative. The search for diagnostic markers in terms of iron metabolism may open up new possibilities for the diagnosis of pulmonary tuberculosis.

Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis

Iron dyshomeostasis is implicated in Alzheimer’s disease (AD) alongside β-amyloid and tau pathologies. Despite the recent discovery of ferroptosis, an iron-dependent form cell death, hitherto, in vivo evidence of ferroptosis in AD is lacking. The present study uniquely adopts an integrated multi-disciplinary approach, combining protein (Western blot) and elemental analysis (total reflection X-ray fluorescence) with metabolomics (1H nuclear magnetic resonance spectroscopy) to identify iron dyshomeostasis and ferroptosis, and possible novel interactions with metabolic dysfunction in age-matched male cognitively normal (CN) and AD post-mortem brain tissue (n = 7/group). Statistical analysis was used to compute differences between CN and AD, and to examine associations between proteins, elements and/or metabolites. Iron dyshomeostasis with elevated levels of ferritin, in the absence of increased elemental iron, was observed in AD. Moreover, AD was characterised by enhanced expression of the light-chain subunit of the cystine/glutamate transporter (xCT) and lipid peroxidation, reminiscent of ferroptosis, alongside an augmented excitatory glutamate to inhibitory GABA ratio. Protein, element and metabolite associations also greatly differed between CN and AD suggesting widespread metabolic dysregulation in AD. We demonstrate iron dyshomeostasis, upregulated xCT (impaired glutathione metabolism) and lipid peroxidation in AD, suggesting anti-ferroptotic therapies may be efficacious in AD.

STUDY OF HAEMOGLOBIN, IRON AND FERRITIN LEVELS IN PRETERM DELIVERY

Introduction: Preterm birth (PTB) is a major determinant of neonatal mortality and morbidity. Preterm babies are prone to serious illness or death during the neonatal period. PTB is one of the unresolved problems in clinical obstetrics and one of the greatest threats to the developing fetus, there is need to determine predictive biomarker for preterm delivery. Therefore present study aimed to assess serum levels of haemoglobin, iron and Ferittin in preterm and full-term delivery&#x0D; Materials &amp; Methods: The present study includes total 80 subjects that comprise forty women presenting with preterm onset of labor followed by delivery and forty women who delivered at term served as controls. Blood Samples from the patients were obtained for haemoglobin, iron and ferritin estimation, when patient was in labor. Serum Iron was estimated by coral clinical kit method. Serum ferritin was performed by Electrochemiluminescence method. Haemoglobin levels were measured by automated haematology analyser.&#x0D; Results: Serum ferritin levels were significantly increased (P&lt;0.001) in preterm delivery as compared to full term delivery. Haemoglobin levels are significantly decreased in preterm delivery (p&lt;0.001) as compared to full term delivery. Serum iron levels were non significantly increased in preterm delivery as compare to the full-term delivery. (P ≤0.05).&#x0D; Conclusion: Our study showed that low levels of Haemoglobin and elevated ferritin levels may be associated with preterm delivery in asymptomatic pregnant women. Though ferritin is an acute phase reactant is elevated in women predisposed to preterm delivery.&#x0D; Keywords: HAEMOGLOBIN, IRON, FERRITIN, PTB, CVF, BMI

Identification of Early Predictive Markers of Toxicity and Efficacy in Patients with DLBCL Treated with Axicabtagene Ciloleucel

<h3>Objective</h3> CAR T cells have been extensively investigated using constructs targeting CD19+ B cells for lymphoid malignancies demonstrating efficacy (Neelapu NEJM 2018; Schuster NEJM 2018). One of the main challenges of adoptive T cell therapy are immune mediated toxicities of cytokine release syndrome (CRS) and neurotoxicity (NT). Despite impressive objective response rates, durable responses are only seen in approximately 40% of patients treated in the pivotal axicabtagene ciloleucel (axi-cel) and tisagenlecleucel trials, highlighting the need for better understanding of the mechanisms of toxicity and efficacy. We aimed to evaluate the association of early biomarkers with severe toxicity and day 90 outcomes in patients treated with commercial axi-cel in a real world setting. <h3>Methods</h3> Seventy-five patients treated with commercial axi-cel were included in this analysis. Baseline characteristics are summarized in Table 1. Patient serum samples were collected at baseline (within 30 days of conditioning chemotherapy), and then daily thereafter starting at the day of axi-cel infusion. Serum cytokine samples were analyzed using the Ella multiplex assay system. Cytokines analyzed include IL1b, IL2, IL6, IL15, TNFa, IFNg, Angiopoietin 1 and 2, as well as CRP and ferritin. Toxicities were graded daily using ASTCT consensus guidelines and retrospectively confirmed. Outcomes were evaluated at day 90 by the treating physician according to the International Working Group Response Criteria for Malignant lymphoma. P values were calculated using Wilcoxon rank sum test. <h3>Results</h3> We observed that baseline levels of CRP (p=0.0018) and Angiopoietin 2/1 ratio (p=0.0092) were associated with grade ≥3 [n=16] neurotoxicity Figure 1A-B). Baseline elevated levels of CRP (p=0.0413) and Ferritin (0.0264) were associated with more grade ≥3 CRS [n=16] (Figure 1C-D). Baseline elevated levels of CRP(p=0.0016), ferritin(p=0.0096) and IL6 (p=0.0029) were associated with poor outcomes at D90 defined as stable disease, progressive disease or death (Figure 1E-G). <h3>Conclusion</h3> We demonstrate that baseline biomarker profile can identify patients at highest risk of developing severe toxicity and/or and treatment resistance highlighting the need to validate these findings in prospective studies. Patients in this poor outcome cohort may benefit from clinical trials evaluating prophylactic agents or more combination therapies to ameliorate severe toxicities or increase response rates.

Relationship of CRP and Ferritin Levels and Length of ICU Stay in Patients with B-Cell Lymphomas Treated with Axicabtagene Ciloleucel (axi-cel)

Background Axicabtagene ciloleucel (Axi-cel) is an autologous chimeric antigen receptor (CAR) T-cell therapy which is effective in relapsed/refractory (R/R) anti-CD19 B-cell leukemia and lymphomas. Axi-cel is associated with unique toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Management of these toxicities often requires ICU admission. Scoring systems have been developed to grade severity of these toxicities and help guide treatment escalation as needed; however, they provide little insight into duration of ICU stay. C-reactive protein (CRP) and ferritin are serum inflammatory markers associated with onset and persistence of CAR-T cell related toxicity. Here, we examine the relationship between these serum inflammatory markers and the duration of ICU stay in CAR-T Cell therapy recipients. Methods We conducted a retrospective analysis of patients (pts) treated with axi-cel across two Mayo Clinic campuses (Jacksonville and Phoenix) from 06/01/2018 until 07/01/2019. Primary objective was to examine the relationship between serum ferritin and CRP levels with need for and length of ICU stay in axi-cel treated pts. Results Our study population consisted of 18 pts (11 males, 61%), median age of 51 (26-67) years. Nine were admitted to the ICU during their initial hospitalization. The median time from axi-cel infusion to ICU admission was 4 (2-8) days with a median ICU length of stay of 4 (2-24) days. All 9 admitted pts developed CRS: grade 1 (1), grade 2 (7), and grade 3 (1); 7 pts developed ICANS: grade 2 (1), grade 3 (1) and grade 4 (5). Eight of the 9 non-ICU pts developed CRS: grade 1 (5) and grade 2 (3). Three pts developed grade 1 ICANS. Grade of CRS and ICANS were higher in ICU pts vs non-ICU pts (p=0.01 and p=0.001, respectively). There was no correlation between the severity of CRS and length of ICU stay (correlation of 0.07, p=0.86) or severity of ICANS and length of ICU stay (correlation of 0.36, p=0.35). Initial median CRP level at infusion was higher in ICU vs. non-ICU pts (25.2 mg/L vs. 13.9 mg/L); however, this difference was not significant, p=0.38. Initial ferritin levels at infusion were over 2-fold higher, albeit not statistically significant, in ICU pts (837 mcg/L vs 387 mcg/L, p=0.21). The median CRP at the time of ICU admission was 54.1 mg/L (3.2-341) mg/L. There was no significant correlation between CRP levels at time of ICU admission and length of ICU stay (correlation of 0.067, p = 0.86). The median ferritin level at the time of ICU admission was 2010mcg/L (344-10943). There was a strong direct correlation between serum ferritin levels and length of ICU stay (correlation of 0.93, p = 0.0003). Conclusions This study showed that an elevated ferritin level at the time of escalation of medical care may be indicative of anticipated prolonged ICU hospitalization in axi-cel recipients.

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13).Case presentationAn 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13.ConclusionsIt is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

Болезнь Стилла у взрослых в практике врача-инфекциониста

Adult-onset Still’s disease (AOSD) is a rare multisystem disease of unknown etiology. According to the literature, AOSD incidence in the world is 0.1–0.4 per 100 thousand population and it has two age-related peaks: the first peak — young age (15–25 years), the second — in persons aged 35–46 years. The causes and pathogenetic mechanism of AOSD are not established. The infectious pathology nature has not received proper scientific confirmation. According to modern concepts, this disease belongs to the group of auto-inflammatory, occurring without autoimmune disorders. It was found that patients with AOSD have a T-cell regulation disorder, increased production of the proinflammatory cytokine, the long-term persistence of which leads to the occurrence of fever and aseptic inflammation in various organs and tissues. The main criteria for this nosology are young age, persistent fever, arthritis, maculopapular rash, elevated ferritin level, neutrophilic leukocytosis, seronegative rheumatoid arthritis. Concomitant diseases include polyserositis, lymphadenopathy, hepatosplenomegaly, and nasopharyngeal infection. The article presents a clinical case of AOSD verified in a young woman at the Infectious Diseases Clinical Hospital. The difficulties of diagnostics are described, taking into account the variety of symptoms and the absence of pathognomonic disease signs. KEYWORDS: Adult-onset Still’s disease, fever, auto-inflammatory disease, arthritis, maculopapular rash, ferritin. FOR CITATION: Kharlamova T.V., Smirnova T.Yu., Golub V.P. et al. Adult-onset Still’s disease in the clinical practice of infectious disease physician. Russian Medical Inquiry. 2020;4(11):705–709. DOI: 10.32364/2587-6821-2020-4-11-705-709.

Significance of Hematological Parameters and Biochemical Markers in Severe Forms of Covid-19

"SARS-CoV-2 is a new virus that affects the human population, about which not all the details are known, and for which the research is ongoing. Several common in vitro diagnostic tests have been implicated in the unfavorable progression of COVID-19, providing potentially important prognostic information. According to some synthesis studies, the progressively low values of the lymphocyte / leukocyte ratio, and progressively increased of the neutrophil / lymphocyte and neutrophil / platelets ratios, correlate with the more severe evolution of COVID-19. The existence of a number of lymphocytes &lt;20% on day 10-12 indicates a pre-severe condition, and a number of &lt;5% on days 17-19 indicates a critical one. D-dimers are the most important prognostic element in monitoring patients with severe forms of COVID-19. Elevated levels of D-dimers compared to the reference biological interval observed at hospitalization of patients with COVID-19 and their marked increase, up to 3-4 times the initial value, were associated with increased mortality, which probably reflects the activation of coagulation in infection / sepsis, cytokine storm and imminent organ failure. Increasing ALT values by more than 5 times the reference biological interval increased the risk of mortality of patients with COVID-19 by seven times. High levels of AST compared to the biological reference range were observed in both patients with non-severe COVID-19 disease as well as in a double the number of patients with severe disease. The value of serum creatinine at hospitalization is a predictor of the death of hospitalized patients for COVID-19. More frequent measurements of serum creatinine are recommended in the management of COVID-19 to improve the early detection of renal lesions in patients with COVID-19. At patients confirmed with COVID19, elevated levels of highly sensitive troponin I (hs-cTnI) were observed during hospitalization, and more than 50% of those who died had a significantly higher concentration of hs-cTnI compared to the biological interval of reference. Hyperferritinemia has been associated with an increased severity of COVID-19 disease, because of elevated ferritin levels compared to the reference biological range, the so-called ""cytokine storm"" is developed which can be fatal for half of COVID-19 patients, especially for the elderly. Lactate dehydrogenase (LDH) has been associated with altered outcomes in patients with viral infections. In an American study (n = 1532 COVID-19 patients), the association between elevated LDH levels (that were measured as soon as possible after hospitalization ) and the severity of the disease in patients with COVID-19 was assessed. Elevated LDH levels were associated with a 6 fold increase in the chance of developing severe symptoms and a 16 fold increase in mortality in patients with COVID-19. C-reactive protein (CRP) is part of the acute phase plasma proteins. COVID-19 increases CRP. This seems to correlate the severity and prognosis of the disease. Studies have found low levels of PCR in patients who do not require oxygen therapy (mean 11 mg / L,) compared to patients who have become hypoxemic (mean 66 mg / L)."

Evaluation of Serum Ferritin as a Prognostic Marker in Acute Hemorrhagic Stroke.

Background Acute hemorrhagic stroke (AHS) resulting from intracerebral hemorrhage (ICH) is a rampant neurological disorder with devastating consequences, particularly in Indians. Recently, serum ferritin levels have been related to adverse cardiovascular and stroke outcomes. We aimed to evaluate the prognostic utility of serum ferritin in AHS. Materials and Methods Admission serum ferritin levels were estimated in 50 AHS patients with primary supratentorial hemorrhage. Study subjects were categorized based on their prognostic scores in modified Rankin scale (mRS) assessment. Ferritin levels were compared across the study groups, correlated with mRS and other ICH severity indicators. Results Serum ferritin and other ICH severity indices such as Glasgow coma scale (GCS) and ICH volume were significantly altered in the mRS groups by the end of 7th and 30th days of hospitalization. Elevated ferritin levels, ICH volume together with decreased GCS, characterized the groups with adverse prognosis. Serum ferritin moderately correlated with GCS ( r = –0.643), ICH volume ( r = 0.562), and had significantly higher correlations with long-term prognostic scores of 7th day mRS ( r = 0.802) and 30th day mRS ( r = 0.916). Conclusion Elevated admission serum ferritin levels indicate poor AHS short-term and long-term outcomes, thereby making serum ferritin a possible prognostic index for the same.