Absolute Neutrophil Count Values Research Articles

Post-Radiotherapy Exosomal Non-Coding RNA and Hemograms for Early Death Prediction in Patients with Cervical Cancer.

Concurrent chemo-radiotherapy (CCRT) is linked with accelerated disease progression and early death (ED) in various cancers. This study aimed to assess the association of plasma levels of exosomal non-coding ribonucleic acid (RNA) (ncRNA) and blood cell dynamics with ED prediction in patients with cervical cancer undergoing CCRT. Using propensity score matching, a comparison of complete blood counts (CBCs) was performed among 370 CCRT-treated patients. Differences in ncRNA and messenger RNA (mRNA) expression before and after CCRT in 84 samples from 42 patients (cohort 2) were represented as logarithmic fold change (log2FC). Networks were constructed to link the CBCs to the RNAs whose expression correlated with ED. From the key RNAs selected using multiple regression of all RNA combinations in the network, CBC dynamics-associated ncRNAs were functionally characterized using an enrichment analysis. Cohort 1 (120 patients) exhibited a correlation between elevated absolute neutrophil counts (ANC) and ED. Cohort 2 exhibited a prevalence of microRNA (miR)-574-3p and long intergenic non-protein coding (LINC)01003 ncRNA, whose expression correlated with ANC and hemoglobin values, respectively. Conversely, acyl-coenzyme A thioesterase 9 (ACOT9) mRNA was relevant to all CBC components. An integrative analysis of post-CCRT ncRNA levels and CBC values revealed that the patients with miR-574-3p-LINC01003-ACOT9 log2FC) < 0 had a better prospect of 30-month disease-specific survival. These findings indicate that miR-574-3p and LINC01003 could serve as ED prognostic biomarkers.

Analysis of the Risk of Infection Stratified By Absolute Neutrophil Counts during Deferiprone-Associated Severe Neutropenia or Agranulocytosis

Introduction Patients with transfusional iron overload receiving iron chelation therapy with deferiprone may experience a decrease in absolute neutrophil counts (ANC) that range from mild (ANC &amp;lt;1.5 x 10 9/L) to severe neutropenia/agranulocytosis (typically defined as ANC &amp;lt;0.5 x 10 9/L), and which put them at risk for infections. In patients taking deferiprone, the risk of infection and/or mortality associated with ANC of &amp;lt;0.2 or &amp;lt;0.1 x 10 9/L is unknown. Our objective was to analyze data from patients taking deferiprone in clinical trials and the postmarketing setting to determine the incidence and severity of infection stratified by ANC levels. s Methods The clinical trial setting involved patients with systemic iron overload who had thalassemia, sickle cell disease, or other anemias and received deferiprone across 15 clinical trials. Data associated with episodes of severe neutropenia/agranulocytosis in patients who had been treated with at least 1 dose of deferiprone were reviewed. For the postmarketing setting, all individual case safety reports since the first market approval of deferiprone on August 25, 1999 to August 31, 2021, were reviewed; cases coded to agranulocytosis were extracted; cases without any reported ANC were removed; and cases with at least 1 ANC value were analyzed. Obtaining confirmed ANC value was not always possible in the postmarketing setting. All infections occuring within ±2 weeks of agranulocytosis onset were identified, graded for severity, and classified as serious, including fatal or life-threatening. Serious events were defined as any event that resulted in death, was life-threatening, required hospitalization or prolonged existing hospitalization, caused disability or permanent damage, caused congenital anomaly, or was classified as an important medical event. Infection events associated with ANC values were categorized into 3 groups based on the nadir ANC (all x 10 9/L): Group A, ANC ≥0.2 to &amp;lt;0.5; Group B, ANC ≥0.1 to &amp;lt;0.2; or Group C: ANC &amp;lt;0.1. Results A total of 977 patients with systemic iron overload received deferiprone in sponsored clinical trials. Among those, 9 patients were in Group A, 3 in Group B, and 10 in Group C. Of the 12 patients in Groups A and B, none had serious, severe, or fatal infections ( Table 1). Three of the 10 (30.0%) patients in Group C experienced serious or severe infections that included (1) parvovirus infection accompanied by diarrhea, a maculopaular rash, and pyrexia resulting in hospitalization; (2) a severe but nonserious respiratory tract infection with esophageal candidiasis in a patient with a history of neutropenia prior to initiating deferiprone; and (3) a fatal case of Pseudomonal sepsis in a patient who had a history of multiple cardiac and pulmonary comorbidities. Deferiprone was permanently discontinued in all 3 patients. From postmarketing data, of a total of 238 adverse reactions that were coded as agranulocytosis, 176 had at least 1 ANC value. Among those, 65 reactions were in Group A, 20 in Group B, and 91 in Group C. Among the reactions in Group A, 5/65 (7.7%) had serious infections and 3 of them (4.6%) had fatal outcomes due to sepsis ( Table 2). Among the reactions in Group B, 2/20 (10.0%) had serious infections, with a fatal outcome in one of them (5.0%); the death was from sepsis and the life-threatening infection involved pneumonia with multiple pulmonary complications. Among the reactions in Group C, 12/91 (13.2%) had serious infections and 8 of them (8.8%) had fatal outcomes; the 8 deaths were associated with sepsis. The 4 serious non-fatal infections involved sepsis; pancytopenia with ANC nadir of 0 accompanied by oropharyngeal pain, fever, and diarrhea that required hospitilization; angioinvasive mucormycosis; and disseminated herpes simplex accompanied by sepsis, resulting in hospitalization. Conclusion Patients receiving deferiprone who become neutropenic are generally at a higher risk of infections or mortality with lower neutrophil levels (ie, ANC &amp;lt;0.2 or &amp;lt;0.1 x 10 9/L compared with ANC ≥0.2 to &amp;lt;0.5 x 10 9/L). Our findings are consistent with the recently published guidelines from the European Hematology Association and the European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias that used agranulocytosis to describe events with ANC of ≤0.2 x 10 9/L in association with a high risk of severe and life-threatening infections.

Patterns of Nonadherence to Hydroxyurea in Pediatric Sickle Cell Disease

Background: Sickle cell disease (SCD) affects an estimated 100,000 American children and adults (CDC, 2017). Hydroxyurea is the first-line disease-modifying treatment for SCD. Daily oral hydroxyurea significantly reduces the frequency of pain and serious medical complications associated with SCD, including dactylitis and acute chest syndrome (Wang et al., 2011). However, adherence to hydroxyurea is less than optimal at 74% among pediatric patients, with 20% of children who are prescribed hydroxyurea taking less than 50% of their prescribed doses (Louiselle et al., 2016). Suboptimal hydroxyurea adherence is associated with increased risk for medical complications, diminished quality of life, and higher health care costs and utilization (e.g., Badawy et al., 2017; Thornburg et al., 2010). Factors associated with hydroxyurea nonadherence in pediatric SCD include female sex, older age, more adherence barriers (e.g., difficulty obtaining refills), lower socioeconomic status, and lower parent treatment knowledge. Purpose: This study aims to characterize trajectories of pediatric hydroxyurea adherence to identify subgroups that may be at highest risk for hydroxyurea nonadherence (e.g., sociodemographic factors), critical time periods for adherence support interventions (e.g., adolescence), and minimal adherence thresholds to optimize hydroxyurea efficacy. Methods: Retrospective chart review across two institutions (i.e., Cincinnati Children's Hospital Medical Center and Nemours Children's Hospital, Delaware) are ongoing. Participants will include patients with SCD ages 2 to 21 years who were prescribed hydroxyurea from March 2007 to February 2017. Researchers are extracting the following data from patient electronic medical records (EMRs) to estimate hydroxyurea adherence: hemoglobin F levels (HbF), mean corpuscular volume (MCV), and absolute neutrophil count (ANC). Additional clinical information will be extracted from patient EMRs including demographic information, SCD genotype, SCD complications, acute care utilization, medical and social complexity, and concomitant medication use. Descriptive statistics will be used to summarize demographic and clinical characteristics of the sample. MCV will be the primary measure of hydroxyurea adherence and Hgb F and ANC will be secondary measures. If the final sample size is sufficiently large, we will conduct group-based trajectory modeling (GBTM) to analyze patterns of hydroxyurea adherence changes over time and identify hydroxyurea adherence trajectory subgroups. Multinomial logistic regression analyses will be used to analyze potential predictors of hydroxyurea adherence trajectory subgroup membership. Results: Preliminary results revealed that as of February 2017, 88% of eligible patients (based on age) were prescribed hydroxyurea.Data from the first 30 completed chart reviews indicates that half of the sample was female (sex assigned at birth), all identified as Black or African American, all but two participants had HbSS, and the mean age 13.0 years ( SD=8.0, range=2.47 to 26.81). Average MCV across an average of 21 time points ( SD=14.2, range=5-74) was 94.3 ( SD=11.2, range=58.4-114.2). As of February 2017, 53% of individuals had MCV values at or above 100. Specifically, 60% of 5-9 year olds, 47% of 10-15 year olds, and 46% of 16+ year olds had MCV values at or above 100. Average Hgb F across an average of 21 time points ( SD=15.3, range=3-81) was 22.9 ( SD=9.3, range=2.6-44.8). As of February 2017, 50% of individuals had HbF values at or above 20.0. Specifically, 55% of 5-9 year olds, 32% of 10-15 year olds, and 55% of 16+ year olds had HbF values at or above 20.0. Average ANC (at non-ill visits) across an average of 20.0 time points ( SD=13.6, range=5-71) was 3,965 ( SD=1,227; range=1,600-6,910). As of February 2017, 31% of individuals had ANC values less than 3,000. Specifically, 20% of 5-9 year olds, 34% of 10-15 year olds, and 30% of 16+ year olds had ANC values less than 3,000. Discussion:Results from this study have the potential to help researchers and clinicians better understand patterns and correlates of hydroxyurea adherence in pediatric SCD patients that can be targeted in future interventions.

Phase II Study Assessing Safety and Preliminary Efficacy of High Dose Intravenous Ascorbic Acid in Patients with TET2 Mutant Clonal Cytopenias

Background: Clonal cytopenia(s) of undetermined significance ( CCUS) is defined as persistent cytopenias arising in the context of myeloid neoplasm ( MN)-associated somatic mutations ( MT) in hematopoietic stem cells. Patients ( PTs) with TET2MT CCUS have a high probability of progression to MN. To date, no FDA-approved therapies exist for CCUS, and PTs often have similar cytopenias/transfusion needs as those with myelodysplastic syndromes ( MDS). TET2 is an ascorbic acid (AA)-dependent dioxygenase that catalyzes the conversion of 5-methylcytosine ( 5mC) to 5-hydroxymethylcytosine ( 5hmC), providing rationale to study high-dose IV (HI)-AA in TET2MT CCUS. Here we report the final results of this pilot trial. Methods: This is an investigator-initiated, single-institutional, phase II trial assessing the safety and efficacy of HI-AA in PTs with TET2MT CCUS (NCT03418038). PTs≥ 18 years with ≥1 TET2MT with or without additional somatic MTs, without prior treatment, and with any of the following laboratory criteria: (1) hemoglobin ( Hb) ≤10g/dL, (2) absolute neutrophil count ( ANC) ≤1(10^9/L), (3) platelet count ( PLT)≤100 (10^9/L) were eligible. HI-AA (1g/kg, maximum 100g) was given 3 times weekly for 12 weeks. The primary endpoint was hematologic response rates determined by MDS IWG 2018 criteria at week 20. (Platzbecker Blood 2018) and reported as hematologic improvement ( HI)- erythropoietic ( HI-E), platelets ( HI-P), neutrophils ( HI-N). Secondary endpoints include safety and adverse events ( AEs), graded by NCI-CTCAE v4.03. Correlative studies include changes in TET2MT variant allele fraction ( VAF), in vitro colony formation and differentiation, global and sequence-specific DNA methylation/hydroxymethylation, and quantitative 5hmC estimated by IHC in bone marrow biopsy specimens. Results: Ten patients were enrolled, with a median age of 71.4 (range: 65, 79) years, 8 (80%) males. The median number of mutations was 3, with 9 (90%) having co-mutations. All PTs but one [-Y] had normal karyotype. Baseline Hb levels were normal in all but one who was red blood transfusion dependent. Five (50%) PTs were thrombocytopenic, and 5 (50%) PTs had ANC&amp;lt;1 (10^9/L). ( Table). HI-AA was well tolerated with the most common AEs being infusion-related polyuria (40%) and polydipsia (40%, 3 Grade 1, 1 Grade 2). One (10%) PT had constipation and headaches (both Grade 1), and 1 (10%) experienced dyspepsia. No treatment-related Grade 3 or 4 AEs' or deaths were reported. The median follow-up duration was 16.8 months (range: 9.4, 24.1). Overall, no PTs met the criteria for HI. There were no significant differences with regards to median Hb, PLT, and ANC values at baseline, week 20, and 1-year (median Hb: 13.3, 12.5, and 12.7 g/dL, p=0.93; PLT: 97 vs. 120 vs. 92.5X10^9/L, p&amp;gt;0.99, and ANC: 0.9 vs. 1.2 vs. 1.3X10^9/L, p=0.99). By CTCAE grading criteria for cytopenias, 3 (30%) PTs had an improvement in severity of cytopenias, while 2 had worsening. One (10%) PT had an improvement in PLT (baseline vs. week 20: 62 vs 192X10^9/L) but was morphologically deemed to meet criteria for CMML-1 at week 20. Four (40%) PTs met criteria for disease progression (PT_4, 7,8,10); CMML-1- 2 and MDS-2. The median time to progression was 5 months (95% CI: 4.9, unreached). Two PTs had mutational clonal evolution, with 1 (PT_8) acquiring a RUNX1 (VAF: 20%) and 1 (PT_9) acquiring 2 CBL mutations (both VAF:4%) at one-year follow-up. There were no significant differences regarding the clinical characteristics or the TET2 variants between PTs who had stable disease vs. progression. There were no significant differences in TET2 VAF at baseline, week 20, and 1-year (median: 39% vs. 43% vs. 42%, p=0.54). We profiled changes in 5-mC and 5-hmC (Ilumina EpicArray) in PTs pre- and post-IV AA treatment and did not observe global changes. However, we were able to highlight site-specific changes in differentially methylated regions, largely resulting in hypomethylation at enhancer sites and affecting actively transcribed states in PTs with an improvement in cytopenia(s) severity by CTACE criteria ( Figure). Conclusion: We report the final safety and efficacy analysis of HI-AA in PTs with TET2 MT CCUS. The trial data suggest that HI-AA is safe and well tolerated. Although there were no significant responses by IWG MDS criteria, alleviation in severity of cytopenias in a subset of PTs (n=3) along with correlative epigenetic changes in enhancer regions, needs further exploration.

Evaluating the epidemiology of clozapine-associated neutropenia among people on clozapine across Australia and Aotearoa New Zealand: a retrospective cohort study

Clozapine is associated with the risk of serious neutropenia. However, this risk might decrease over time, meaning that indefinite absolute neutrophil count (ANC) monitoring could be unnecessary. We aimed to determine the epidemiology and timing of clozapine-associated neutropenia outcomes, to investigate variables that might contribute to the odds of neutropenia, and to determine risk of competing neutropenic events during clozapine treatment. We performed a retrospective analysis of the Australian and New Zealand Viatris Pharmacovigilance system (one of two monitoring databases for these two countries) between June 6, 1990, and Oct 25, 2022. Patients were excluded from analysis if they commenced clozapine before 1990, did not have a haematology test within 2 weeks of commencement date, or had no follow-up. We measured minor neutropenia (ANC 1·0-1·5 × 109 per L) and serious neutropenia (ANC <1·0 × 109 per L) leading to cessation of clozapine within 6 weeks of the neutropenic event. We determined the rates of minor and serious neutropenia and calculated odds ratios (ORs) for the likelihood of neutropenia leading to cessation. For serious neutropenia leading to cessation, we used time-to-event to calculate rolling weekly averages and to perform competing risk analysis of outcomes using Cox proportional hazards models and a Fine-Gray subdistribution hazards regression model. For the subset of data where information on previous clozapine use was available, we did an analysis for participants who did and did not have previous clozapine exposure. We included 26 630 people, with 2·6 million ANC values. Within the total cohort, 17 585 people (66%) were male, 9025 (33·9%) female, and 20 (0·1%) other gender, and the mean age was 36·1 years (SD 13·7). We did not have data on race or ethnicity. Of the 26 630 people taking clozapine, 1146 (4·3%) had minor neutropenia, 313 (1·2%) had serious neutropenia leading to cessation, and 223 (0·8%) had serious neutropenia unrelated to clozapine without cessation. In people with no previous exposure to clozapine (n=15 973), the cumulative incidence of serious neutropenia leading to cessation was 0·9% at 18 weeks and 1·4% at 2 years; the weekly incidence rate for serious neutropenia leading to cessation peaked at 9 weeks (0·128%) and fell to a rolling average weekly incidence of 0·001% by 2 years. For minor neutropenia, the cumulative incidence was 1·7% at 18 weeks and 3·5% at 2 years; the weekly incidence rate peaked at 9 weeks (0·218%) and fell to a stable rolling average of 0·01%. The median time to a serious neutropenic event leading to cessation was 17 weeks (IQR 9·96-102). Previous clozapine exposure reduced the risk of serious neutropenia leading to cessation (OR 0·19, 95% CI 0·12-0·31; p <0·0001). Most serious neutropenia leading to clozapine cessation occurs within 18 weeks of treatment and becomes negligible after 2 years. Weekly haematological monitoring after the first 18 weeks could be safely reduced to once every 4 weeks and ceased after 2 years unless clinically indicated. Clozapine retrial after interruption with 2 cumulative years of unremarkable testing might not require further haematological monitoring. A serious neutropenia ANC threshold of ≤1·0 × 109 per L could be used in more jurisdictions. None.

Outcomes of Antithymocyte Globulin and Cyclosporine for Severe Aplastic Anemia

Background: Aplastic anemia (AA) is mediated by T cell destruction of hematopoietic stem and progenitor cells causing pancytopenia and bone marrow hypoplasia. The current standard of care for severe aplastic anemia (SAA) is hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CsA) with or without eltrombopag (Epag), a thrombopoietin receptor agonist. HSCT is preferred for SAA in young adults as a curative option, but only a small proportion of patients have histocompatible siblings and mortality increases with age. The IST plus CsA combination with or without Epag has led to survival rates comparable with those observed with HSCT recipients. However, complete hematologic remission is rare with IST and there is a considerable risk of clonal complications, including PNH evolution and progression to MDS. The aim of this study was to evaluate outcomes of ATG plus CsA therapy in a large cohort of SAA patients. Methods: We retrospectively analyzed medical records of 156 patients with SAA, aged ≥2 years treated with ATG plus CsA with or without Epag at our institution between July 2000 and January 2023. Hematologic responses were evaluated at 3-, 6- and 12-months post therapy initiation. Super response (SR) was defined as hemoglobin ≥12 g/dL, platelet count ≥150x10 9/L and absolute neutrophil count (ANC) ≥1.0x10 9/L; complete response (CR) was defined as hemoglobin ≥10 g/dL, platelet count ≥100x10 9/L and ANC ≥1.0x10 9/L. Partial response (PR) was defined as not meeting the criteria for CR and SAA. Overall response encompassed SR, CR, and PR. Statistical analyses were performed with the use of Chi-squared test and Kaplan Meier method. Results: The median age at diagnosis was 52 (IQR 30-66) years, 47% were male, and 86% were Caucasian. Twenty three percent of the cohort had coexisting paroxysmal nocturnal hemoglobinuria. Most patients were treated with ATG plus CsA (92%), the remaining 8% additionally received Epag. Overall response rates were 70%, 67%, and 77% at 3-, 6- and 12-months post-treatment initiation, respectively. CR was achieved in 10%, 15%, and 18% at 3-, 6- and 12-months, respectively. SR was achieved in 16.3% of patients at 12 months, as shown in Figure 1. Patients who achieved SR were young with median age at diagnosis of 28 years, while those who achieved PR or no response had a median age of 54 and 56 years, respectively. Patients who responded to the ATG + CsA therapy had significantly higher baseline ANC (p=0.04), absolute reticulocyte count (ARC) (p&amp;lt;0.001) and absolute lymphocyte count (ALC) (p&amp;lt;0.001). Pre-treatment median values of ANC, ARC and ALC were higher for patients who achieved SR compared to the rest of responders. With a median follow up time of 4.5 years, the estimated median relapse free survival was 9.2 years (95% CI, 3.2 - not reached [NR]) (Figure 2). Of the entire cohort, 21 (13%) patients progressed to acute myeloid leukemia or myelodysplastic syndrome. At data cut off, a total of 66 patients had died; the estimated median OS was 11.6 years (95% CI, 8.4 - NR). In particular, 30 patients died within the first 12-months, 13 within 3-months of ATG initiation from treatment-related complications, 6 from pneumonia and the rest from unknown causes. Conclusion: The findings of our study demonstrate that ATG plus CsA is an effective and safe treatment option for patients with SAA, especially in the older patient population where HSCT-related toxicities can lead to high mortality. Those with higher baseline ALC, ANC and ARC were more likely to respond to therapy compared to those with lower counts. A small percentage of patients progressed to myeloid neoplasia. Mortality within the first 12-months was high, indicating the need for close monitoring to avoid treatment-related mortality.

Analytical Performance Evaluation of Three Point-of-Care CBC Analyzers for Management of Clozapine Therapy in Ambulatory Psychiatry Clinics.

Clozapine is a first-line therapy and the only FDA-approved drug for patients with treatment-resistant schizophrenia (TRS). However, frequent measurement of absolute neutrophil count (ANC) is required to monitor for potential adverse severe neutropenia from clozapine therapy. We evaluated 3 point-of-care (POC) instruments that perform the complete blood count (CBC) with differential to assess their analytical performance and potential to meet the clinical need for clozapine therapy management. A CBC with differential was performed on 104 residual whole blood specimens using 3 CBC analyzers (Sight OLO, PixCell HemoScreen, and Sysmex pocH-100i) to assess analytical precision, linearity, and accuracy vs the ADVIA 2120i and manual differential reference methods. Clinical concordance of ANC between POC devices and manual differential at medical decision points for mild, moderate, or severe neutropenia, and the threshold for clozapine therapy discontinuation (1.0 × 109/L) were determined. For CBC parameters, a CV ≤ 6.4% was observed on the OLO, CV ≤ 6.2% for the HemoScreen, and CV ≤ 5.1% with the pocH-100i. Each device accurately identified ANC with the greatest mean bias ±0.42 × 109/L using the pocH-100i vs manual differential. For results near the medical decision points (ANC <1.5 × 109/L), clinical concordance of ANC results was 55.6% for the OLO, 89.5% for the HemoScreen, and 82.4% for the pocH-100i. The HemoScreen device demonstrated the best clinical concordance in ANC values at medical decision thresholds for clozapine therapy management.

The predictive value of hematological markers in renal cell carcinoma.

621 Background: Renal cell carcinoma (RCC), which accounts for about 3% of adult malignancies, is regarded as a major cause of morbidity and mortality. The neutrophil-lymphocyte ratio (NLR) is a simple, reliable, and cost-effective biomarker of systemic inflammation that has been linked to oncologic outcomes in a variety of malignancies. The objective of this study is to determine whether NLR, along with other hematological parameters such as absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and the Systemic Immune-Inflammation Index (SII; defined as neutrophils counts X platelets counts divided by lymphocyte count), are related to baseline distant metastases and overall survival (OS) in RCC patients. Methods: Clinical data from 203 RCC patients treated at King Hussein Cancer Center (Amman, Jordan) were retrospectively reviewed. We examined the relationship between age, sex, ANC, AMC, ALC, AEC, NLR, MLR, PLR, and SII with baseline distant metastasis and patients’ OS. Results: Of the 203 patients, 97 patients (48.5%) were stage 4 at the time of diagnosis. Univariate analysis showed that patients with high baseline ANC (&gt;5400), AMC (&gt;600), AEC (&gt;120), NLR (&gt;4.36), MLR (&gt;0.33), PLR (&gt;140.44), WBC count (&gt;8.2), SII (&gt;757.7) and low baseline ALC (≤1900) had more baseline metastasis. (p-value: &lt;0.001, 0.007, 0.020, &lt;0.001, &lt;0.001, &lt;0.001, 0.006, &lt;0.001, and 0.004, respectively). On multivariate analysis, patients who had elevated NLR (&gt;4.36) were more likely to have distant metastasis at the time of diagnosis (p-value = 0.0076, odds ratio (OR): 4.45, CI: 1.49–13.33). Moreover, univariate and multivariate analysis showed that patients with elevated NLR (&gt;4.36) were associated with poorer OS (p-value: &lt;0.0001 and 0.0065, respectively). In addition, patients with elevated baseline ANC, AMC, MLR, PLR, SII, WBC count, and low ALC values were associated with poorer OS (p-value: &lt;0.0001, 0.0234, &lt;0.0001, &lt;0.0001, &lt;0.0001, 0.0290, and &lt;0.0001, respectively). Conclusions: The results of this study indicate a substantial correlation between several hematological parameters, including NLR, with the presence of distant metastases at the time of diagnosis and OS. Further research is required to uncover whether these hematological markers may be used to identify patients who are more likely to develop metastases and predict treatment response.

Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa

AbstractRealizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include ∼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.

Therapeutic Modulation of the Marrow Microenvironment in MDS: A Phase I Trial of Abaloparatide and Bevacizumab

Background: The bone marrow microenvironment (BMME), including mesenchymal stromal cells (MSCs) and osteolineage cells, vascular endothelial growth factor (VEGF) signaling, and marrow angiogenesis, is altered in myelodysplastic syndromes (MDS). BMME manipulation represents a novel therapeutic strategy for MDS. Preclinical studies have demonstrated that parathyroid hormone (PTH) increases MSC and osteoblast support of hematopoietic stem cells and remodels marrow vascularity. This effect can be augmented with the addition of bevacizumab (BEV), which also decreases angiogenesis. Here we report the results of a phase 1 study of abaloparatide (ABL), a PTH-related protein analog, plus BEV in patients with MDS. Methods: Eligible patients were ≥ age 18 with MDS or non-proliferative chronic myelomonocytic leukemia and at least one cytopenia. Those categorized as very-low to intermediate risk per the Revised International Prognostic Scoring System (IPSS-R) who were treatment-naive or had received only prior growth factors were eligible. Patients of all risk categories who had not responded to disease modifying agents were also eligible. Prior therapies were stopped at least 14-days before study start. Patients received one 28-day cycle of ABL (80 mcg/day self-injected) followed by three 28-day cycles of ABL + BEV (5 mg/kg on days 1 and 15). Bone marrow samples were collected at baseline, after cycles 1 and 4, and 3 months after treatment completion. The primary endpoint was the rate of treatment-limiting toxicities (TLTs). Response rates, impact of therapy on BMME cell populations, and effect on health-related quality of life (HRQoL) and geriatric assessment were additional endpoints. Results: Nineteen patients were enrolled and treated. The majority (n=13) received prior therapy, most commonly with an erythropoietin stimulating agent (ESA; 77%). Typical molecular heterogeneity was present and included mutations in SF3B1 (44%), TET2 (33%), ASXL1 (22%), and DNMT3A (22%). No TP53 mutations were noted. Additional baseline characteristics are outlined in Table 1. Three patients (16%) experienced a TLT: a grade 3 infusion-related reaction and grade 2 fatigue with orthostatic hypotension attributed to ABL, and a grade 3 colonic perforation possibly attributed to BEV. There were no other grade 3 events related to treatment (TRAEs). Frequent (≥15%) TRAEs were: back pain (n=6), chills (n=3), and epistaxis (n=3). Analysis of bone marrow samples revealed a significant increase in mean MSC colony forming units (CFU-Fs) after cycle 1 of ABL compared to baseline (20.7 ± 5.8 vs 36.5 ± 6.4 CFU-F per 1x106 cells, p=0.004). This increase was not maintained with the addition of BEV. Of the 17 patients evaluable after at least 2 cycles on study, 15 (88%) had stable disease and 2 (12%) had progression. Five of 6 patients (83%) with MDS with excess blasts 2, prior hypomethylating agents, and/or high to very-high IPSS-R maintained stable disease over 7 months of follow up. The sixth patient achieved a neutrophil response by 2006 International Working Group criteria after 8 weeks of therapy. In the subset of patients with baseline neutropenia (n=4) there was a significant increase in absolute neutrophil count (ANC) after 8 weeks on study (0.89 ± 0.26 vs 1.28 ± 0.32 103 cells/µL, p=0.04). All patients with baseline neutropenia or thrombocytopenia that had improved ANC (n=4) or platelet counts (n=3), respectively, over the first 8 weeks of treatment, had increased CFU-Fs after cycle 1. Three patients (18%) had decreased transfusion needs over the first 8 weeks despite discontinuation of prior ESAs; all 3 also demonstrated increases in CFU-Fs after cycle 1. HRQoL and geriatric assessments were stable throughout the study. Conclusions: ABL + BEV therapy is safe and well-tolerated in MDS. A significant increase in MSCs was noted following single-agent ABL for 4 weeks, suggesting BMME remodeling. This corresponded with significant early improvements in ANC values and transfusion requirements during the first 8 weeks of therapy in some patients. Prolonged stable disease was maintained in a majority of patients, including several with high-risk clinical features. These data suggest successful manipulation of the BMME with effects on hematopoiesis, and warrant further investigation of longer ABL monotherapy as a new treatment paradigm for patients with MDS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clozapine and Neutropenia in Patients with Schizophrenia and SARS-CoV-2 Infection.

BackgroundClozapine (CLZ) is used for treatment-resistant schizophrenia (TRS). Adverse reactions to clozapine include neutropenia. In March 2020, WHO declared the COVID-19 pandemic and after, psychiatrists raised concerns regarding continuation of clozapine, due to multiple restrictions. We aimed to provide a study on the association between neutropenia and clozapine in patients with schizophrenia and COVID-19.AimTo assess the neutrophil count in patients with schizophrenia treated with clozapine and infected with COVID-19.MethodsThe study patients with schizophrenia, according to DSM-5, admitted to the Clinical Hospital of Psychiatry and Neurology Brasov, Romania, between April 2020 and October 2021. The inclusion criteria included positive RT-PCR (real-time PCR) test for COVID-19 and treatment with clozapine. We assessed three values of ANC (absolute neutrophil count): before COVID-19 infection (last ANC obtained at mandatory check), during infection and 1 month after resolution (first negative PCR test).ResultsOf the 105 cases, 95 did not have neutropenia. Fifty-nine patients were males (62.1%), mean age was 43.5 years (SD = 12.1) with an average of clozapine treatment of 52.4 months (SD = 11.9). At baseline, they had a small reduction in the ANC mean value (4.41 × 109/l; SD = 2.22) which did not constitute a statistically significant decline from the prior to COVID-19 mean value of 4.66 × 109/l (SD = 2.34; p = 0.45). Values were also normal in the first month after negative PCR testing (4.45 × 109/l; SD = 2.35; p = 0.91). A total of 10 patients (9.5%) had neutropenia. The age, dose of clozapine and duration of treatment were not statistically different compared to the group without neutropenia.ConclusionPsychiatrists and other health professionals should keep in mind that neutrophil count may decrease during COVID-19 infection in patients taking clozapine and in some cases, neutropenia may even occur. We assumed that neutropenia could be caused by COVID-19 and clozapine interaction.

Diagnostic utility of combined immature and total neutrophil counts along with C-reactive protein in early detection of neonatal sepsis: A cross-sectional study

IntroductionA timely diagnosis is critical for management of Neonatal sepsis. Blood Culture is considered to be the “Gold Standard” for its diagnosis, but it has some limitations. In recent times, highly sensitive and specific inflammatory markers like interleukins, ELISA, counter immune-electrophoresis etc. have been in use for its diagnosis. But these are impractical for developing countries, due to their high cost and requirement of sophisticated equipments. A combination of haematological parameters like total leucocyte count (TLC), immature to total neutrophil ratio (I/T ratio), absolute neutrophil count (ANC), platelet count and C-reactive protein (CRP) estimation provide an early diagnosis of bacteremia. This study was undertaken to evaluate the usefulness of the above mentioned parameters as indicators for early diagnosis of neonatal sepsis. Material and methodsIn the present cross-sectional study, we intent to analyse various hematologic parameters in 160 neonates admitted in the neonatal care unit of a tertiary care hospital in Delhi. We obtained data from the records of blood culture and complete blood counts of neonates from pathology and microbiology departments of the hospital. Out of 160 admitted neonates, 80 were taken as cases and remaining 80 were taken as controls. Medical records were studied to identify infants born at ≥ 34 weeks gestation. CBCs was analysed, blood cultures and CRP were done in department of Microbiology. CBC, CRP and Blood culture was done as per standard protocols and clinical assesment by paediatrician. The statistical analyses were performed using SPSS version 22 for windows. ResultsAmong 80 neonates, who were in early neonatal sepsis, 44 cases (55%) were females, and 36 (45%) were males. The Microbiological profile of 80 septic neonates was analysed. The I/T value, ANC and CRP values were significantly higher in the neonates suffering from sepsis as compared to the control group. Among 80 septic neonates (cases), 30 (37.5%) were having normal ANC while 50 (62.5%) were having increased ANC and 34 (42.5%) were having normal I:T ratio while 46 (57.5%) were having increased I:T ratio. Out of 80 septic neonates (cases), 18 (22.5%) were having normal CRP while 62 (77.5%) were having increased CRP. ConclusionANC, I/T Ratio and CRP are quick, simple and cost-effective routine laboratory tests which help in early diagnosis of neonatal sepsis. Although there are many serological markers available, ANC and I/T Ratio serves as a reliable predictor of neonatal sepsis. With a good sensitivity, high specificity and a good negative predictive value these parameters can therefore help in timely and early identification of neonatal sepsis.

Manifestation of Large Granular Lymphocyte Leukemia in Pediatric and Young Adult Population Is Distinct from Older Adult Cohorts

Introduction: Large Granular Lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder usually manifested in elderly individuals, with mean age of onset at 65. However, LGL leukemia cases in pediatric and young adult (age <30) populations are occasionally observed. Severity of disease, response to routine LGL treatments (methotrexate, cyclophosphamide, cyclosporine), and molecular profiling of this cohort is largely unknown, with only a few case reports describing the occurrence. Here we present the first comprehensive analysis of pediatric and young adult LGL leukemia patients, where we compare demographic and hematologic parameters, frequency of STAT3 mutations, whole exome and transcriptomic profile, and treatment responses to the older adult (age >50) cohort.Methods: We retrospectively collected clinical data from 23 young adult (age <30), 105 adult (age 30-50), and 89 older adult (age >50) LGL leukemia patients. All participants signed informed consent to provide biospecimens and clinical records to the LGL Leukemia Registry. Whole exome (PBMC and saliva) and RNA sequencing (PBMC) was conducted on 115 patients. Sanger sequencing was utilized to determine STAT3 mutational status in the remaining 102 patients.Results: STAT3 is the most frequently mutated gene in LGL leukemia, and the mutation is associated with lower absolute neutrophil counts (ANC). We observed no differences in the frequency of STAT3 somatic mutations in young adult, adult, and older adult LGL leukemia (p=0.143). However, we detected a significant positive linear relationship between age of the patient and ANC values (p=0.002) for STAT3 mutant patients (Figure 1A). STAT3 wild-type (WT) patients did not display this relationship (p=0.756). No age associated trends were detected for hemoglobin values, although we detected decreasing red blood cell (RBC) values with increasing age for both STAT3 mutated and WT patients (p= 0.031, 0.010, respectively). No difference in sex (male vs female) balance was found within the young adult cohort (p=0.190). As rheumatoid arthritis (RA) is observed in ~30% of LGL leukemia patients, we asked if this prevalence also holds in the younger cohort. RA was observed in similar proportion in all young, adult, and older adult groups (p=1).To compare the severity of disease manifestation between the age groups, we first asked how many patients ever initiated LGL-related treatments in each age group. We found that patients under 50 are more likely to be on LGL related treatments compared to patients over the age of 50 (p=0.016) (Figure 1B). Next, we examined length of survival between age groups. Despite increased initiation of LGL related treatments, no statistically significant difference in overall survival (OS) was observed between patients under 50 and patients over the age of 50 (p=0.33) (Figure 1C). Therefore, we asked if the treatment response in younger patients is better compared to older patients. We observed no statistically significant differences in the routine LGL treatment responses between patients under 50 and patients over the age of 50 (p=0.732).Interestingly, epigenetic and chromatin modifier mutations are equally common in patients 50 years old and under relative to older adult patients (p= 0.271) (Figure 1D). Transcriptomic analysis of the PBMC data revealed enrichment of TNFα signaling in patients older than 50, while IFNα and IFNγ signaling was enriched in patients 50 years old and younger.Conclusions: We report the clinical and molecular analysis of LGL leukemia in pediatric/young adult and adult patients compared to the older adult patients that comprise the majority of LGL cases. We show that while STAT3 mutation frequency is similar across all age groups, younger patients with STAT3 mutation show lower ANC values compared to older patients. Importantly, we show that younger patients exhibit a more severe disease, as indicated by increased initiation of LGL treatment. However, overall survival in younger groups compared to older patients is not impacted. Finally, we show that younger patients display similar proportions of epigenetic and chromatin modifying mutations that are a prominent feature of older patients, and feature enrichment of IFNα and IFNγ signaling distinct from older patients. [Display omitted] DisclosuresFeith: Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees. Loughran: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Keystone Nano: Membership on an entity's Board of Directors or advisory committees; Bioniz Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees.

IDH Mutations Are Enriched in Myelodysplastic Syndromes Patients with Severe Neutropenia: A Potential Targeted Therapy

IDH Mutations Are Enriched in Myelodysplastic Syndromes Patients with Severe Neutropenia: A Potential Targeted Therapy

Real-world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia.

BackgroundCombination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors.MethodsThis study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable.ResultsIn total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203).ConclusionThe effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

Evaluating the Prognostic Role of Monocytopenia in Chemotherapy-Induced Febrile Neutropenia Patients Treated with Granulocyte Colony-Stimulating Factor.

ObjectiveChemotherapy-induced febrile neutropenia is a common and serious oncological emergency which carries a substantial mortality and morbidity. The main objective of this study is to evaluate the usage of absolute monocyte count (AMC) at presentation as a prognostic factor for patients with chemotherapy-induced febrile neutropenia who were subsequently treated with granulocyte colony-stimulating factor (G-CSF).Study DesignThe electronic medical records of our center were used retrospectively to identify patients diagnosed with unprecedented chemotherapy-induced febrile neutropenia treated with G-CSF between January 2010 to December 2020 and diagnosed with solid and hematological malignancies. Patient’s demographics, disease characteristics and laboratory investigations were extracted. Disease progression measures were statistically compared between the study groups in the short-term period of follow-up (six days) including absolute neutrophil count (ANC), ANC difference compared to the baseline readings, hospitalization period, and mortality.ResultsA total of 80 patients were identified and categorized into two groups namely monocytopenia (n = 34) and non-monocytopenia (n = 46) with an AMC cutoff point of 0.1×109 cells/L. The monocytopenia group exhibited a worse prognosis with lower ANC values and slower improvement illustrated by the low ANC difference values at all follow up points (P-value ≤ 0.05) apart from day 5. A statistically significant lower hospitalization period was also observed in the non-monocytopenia group (P-value = 0.006). Linear regression analysis evaluated the association between AMC values at admission and ANC values at admission along with subsequent days of follow up which were found to be statistically significant (P-value ≤ 0.05). Receiver operating characteristic curves suggest a satisfactory predictability of ANC changes by AMC values at admission, days1, 2, 3, 4 and 6.ConclusionMonocytopenia holds a worse prognosis in chemotherapy-induced febrile neutropenia patients treated with G-CSF. In addition, AMC values at presentation represents a potential risk factor that can predict short-term changes regarding ANC measures.

Clinical Dissection of Infectious Event Following ATG Treatment for Aplastic Anemia and Hypoplastic Myelodysplastic Syndrome Reveals Urgent Need for Anti-Aspergillus Prophylaxis

▪BackgroundInfection is the leading cause of death in patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hMDS). Prolonged neutropenia and lymphopenia followed by immunosuppressive treatment (IST) are the major risk factor for the development of infections. While IST responses occur after 3-6months after ATG treatment, aggravation of transient neutropenia and lymphopenia is provoked by ATG treatment. As such, increasing of mortality associated with infection is obviously predictable following ATG treatment. In this study, we analyzed the detailed infection profile so as to guide adequate prophylaxis after ATG treatment in AA and hMDS. More specifically, we studied the relation between invasive fungal infection (IFI) and treatment outcome and predictive factor of IFI after ATG treatment for AA and hMDS.Patient and MethodsWe retrospectively reviewed the medical records of AA and hMDS patients who were treated with rATG based immunosuppressive treatment between January 2005 to July 2016 in two institutions (Seoul National University Hospital and Seoul National University Bundang Hospital). Patients who did not complete the ATG course for 5days and visit the clinic after IST for at least 6months were excluded. Patients treated with hematopoietic stem cell transplantation within 6months after rATG administration were also excluded. The response was evaluated at 3 and 6 months after IST. Assessment of response to IST was performed according the criteria of European Group for Blood and Marrow Transplantation (EBMT). Infection events occurred within 6 months after rATG administration were studied. Only proven and probable IFIs were considered according to the European Organization for Research and Treatment of Cancer/Mycosese Study Group (EORTC/MSG) criteria. Overall survival (OS1) was defined as the time from diagnosis to last follow-up or death from any cause. The time of IST treatment to death was defined as OS2 and also evaluated. To assess t the optimal cut-off value of total white blood cells (WBCs), ALC (Absolute Lymphocyte Count) and ANC (Absolute Neutrophil Count), WBCs, ALC and ANC of the initiation of treatment, 3months after IST and 6months after IST were analyzed by using receiver operating characteristics (ROC) curves.ResultsA total of 139 patients (median age, 51.0; range 15-82, male:female 75:64) were evaluated. Eighty-two percent of the patients were SAA (n=114) at treatment. Response was observed in 97(CR 9.4 %, PR 60.4 %) patients at 3months and in 103 (CR 29.5%, PR 44.6%) patients at 6months after IST. A total of 88 infection events were observed in 75 patients and the most frequent infection was bacterial infection (40 cases, 45.4%). IFIs were observed in 26 cases and invasive aspergillosis (IA) was the most common fungal infection (23 cases, 88.4%). Other fungal infections included one proven mucormycosis by biopsy of nasal cavity and two yeast (Candida tropicalis and Candida albicans) fungemia. The most frequent organ involved by IFI was lung (21cases, 80.7%). The mean time to infection events was 1.6months in 75 patients and 2.0 month in 26 patients with IFIs. 33 patients died during the study period, and 26 of them were related with infection. 13 deaths were directly due to IFIs with median time of IST treatment to death was 17 weeks (range: 2-139weeks) and eight of them expired within 6months after IST. IFIs following ATG was significantly related with shorter OS (HR 4.4; CI 1.925-10.074; P= <0.0001). ALC less than 500/ml (sensitivity 71.4%; specificity 76.9%; AUC 0.768 CI95 0.630-0.906; P=0.002) at 3months after IST was a significant predictive factor for IFIs related death (OR 8.3; CI 2.167-32.044; P=0.002). Interestingly, infections other than IFI were not significantly related to infection related death or shorter OS.ConclusionInvasive fungal infection is the leading cause of death in patients who receive IST for AA or hMDS. Our findings strongly suggest need for antifungal prophylaxis such as posaconzole following ATG based IST in this population. DisclosuresNo relevant conflicts of interest to declare.

When non-Whiteness becomes a condition

AbstractThe term “benign ethnic neutropenia” describes the phenotype of having an absolute neutrophil count (ANC) <1500 cells/μL with no increased risk of infection. It is most commonly seen in those of African ancestry. In addition, ANC reference ranges from countries in Africa emphasize that ANC levels <1500 cells/μL are common and harmless. The lower ANC levels are driven by the Duffy null [Fy(a-b-)] phenotype, which is protective against malaria and seen in 80% to 100% of those of sub-Saharan African ancestry and <1% of those of European descent. Benign ethnic neutropenia is clinically insignificant, but the average ANC values differ from what are typically seen in those of European descent. Thus, the predominantly White American medical system has described this as a condition. This labeling implicitly indicates that common phenotypes in non-White populations are abnormal or wrong. We believe that it is important to examine and rectify practices in hematology that contribute to systemic racism.

Perioperative Indicators of Prognosis in Acute Invasive Fungal Sinusitis.

ObjectiveThe purpose of this study is to identify perioperative independent prognostic factors that are available to the consulting team to aid in determining prognosis in patients with acute invasive fungal sinusitis.Study DesignRetrospective chart review of patients with biopsy-proven acute invasive fungal sinusitis from 2015 to 2018.SettingAcademic tertiary care center.MethodsTwenty-one patients were included from our single-center retrospective review. Kaplan-Meier graphs were created, and the Breslow test used to compare the curves to obtain P values. A univariate Cox regression analysis was performed on the data that were significant at 3 months from diagnosis.ResultsTwenty-one patients were included, and 17 (76%) had an underlying hematologic malignancy. Overall survival was 71% and 52% at 1 and 3 months, respectively, and 94% of patients with hematologic malignancy had an absolute neutrophil count ≤1 at diagnosis. Absolute neutrophil count values and fungal species were not associated with a difference in prognosis. Factors associated with decreased survival included current smoking and the absence of a rhinologist on the treatment team at the initial or subsequent debridement (hazard ratio, 3.03). Laboratory values such as beta-D-glucan and galactomannan were assessed in addition to disease extension at diagnosis.ConclusionThis study presents a retrospective review of a single institution’s experience with acute invasive fungal sinusitis. Subspecialty level of care likely improves overall survival in these patients, whereas current smoking may imply a worse prognosis.

The Diagnostic Value of Fe3+ and Inflammation Indicators in the Death of Sepsis Patients: A Retrospective Study of 428 Patients.

BackgroundStudies have shown that a variety of blood inflammatory markers can be used to assess the criticality of patients with sepsis. In this study, the blood inflammatory factors related to the sepsis survival group and the death group were compared and analyzed, which can be used by clinicians to adjust sepsis patient treatment.MethodsThis study used retrospective methods to analyze the medical records of 428 patients with sepsis. The test of blood samples includes the patient’s age, gender, hospital stays, the concentration of procalcitonin (PCT), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), D-dimer (DD), Fe3+, and hemoglobin (Hb) in the venous blood of patients with sepsis. The detection of PCT methods adopts the sandwich immunofluorescence (IF). ROC curve was used for the diagnosis and analysis of various factors of sepsis.ResultsAmong all the patients with sepsis, 133 patients died, with a mortality rate of 31.07%. Analysis of related inflammatory indicators and the patient’s baseline parameters showed the patients age, the values of PCT, ANC, NLR, and DD in death group were statistically higher than those in survival group (all p values were <0.05). However, the concentration of Fe3+ and ALC show an opposite trend between the two groups. Regression analysis results showed the patient’s gender, Fe3+, PCT, ANC, and DD are all independent prognostic factors for patients with sepsis. The results of the ROC curve of related diagnostic indicators show that DD has the best area under curve (AUC=0.700), the most sensitive index is ANC (74.44), and the most specific index is PCT (89.80). The results of the two-by-two combined diagnosis of the four indicators showed that the PCT+DD group had better AUC (0.748) and specificity (78.23), and the Fe3++DD group had the best sensitivity (75.89).ConclusionIn this study, the patient’s gender and the inflammation-related markers of Fe3+, PCT, ANC, and DD can be used as independent risk factors affecting the prognosis of patients with sepsis. The combination of PCT+DD and Fe3++DD has high diagnostic value for patients with sepsis.