Neutrophilic granulocyte percentage is associated with anxiety in Chinese hospitalized heart failure patients.

BACKGROUND: In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. METHODS: We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. RESULTS: There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. CONCLUSIONS: Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.

Role of immature granulocytes and total bilirubin values in the diagnosis of perforated appendicitis in patients over 65 years.

OBJECTIVE: The aim of this study was to investigate the effectiveness of immature granulocyte count, immature granulocyte percentage, and total bilirubin value in predicting complicated and perforated appendicitis in patients aged 65 years and older with a diagnosis of appendicitis. METHODS: In this study, 84 patients, aged 65 years and older, who had appendectomy demographic information, preoperative white blood cell count, neutrophil/lymphocyte ratio, immature granulocyte count and immature granulocyte percentage, operation findings, and pathology results were collected retrospectively. They were grouped into 4 categories: complicated, non-complicated, perforated, and non-perforated, according to the data and surgical findings. RESULTS: Total bilirubin and immature granulocyte count were found to be statistically significant in predicting complicated and perforated appendicitis in patients aged 65 years and older with a diagnosis of appendicitis. The total bilirubin was found to have the following values in differentiating complicated appendicitis: area under the curve=0.883, sensitivity=78.3%, and specificity=88.5%. Total bilirubin had the highest discrimination power with area under the curve=0.804 in differentiating perforation. CONCLUSION: The immature granulocyte percentage and total bilirubin count are the fast, inexpensive, and reliable parameters that can be used to predict complicated and perforated appendicitis in patients aged 65 years and older.

Predictive value of immature granulocyte and delta neutrophil index in the diagnosis of complicated acute cholecystitis.

OBJECTIVE: The complicated gallbladder disorders are associated with increased mortality and morbidity. Thus, this study was aimed at evaluating the predictive value of immature granulocyte count and delta neutrophil index in the prediction of complicated cholecystitis. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent surgery for acute cholecystitis between January 2018 and April 2022. Overall, 351 patients fulfilling the inclusion criteria were included in the study. In all patients, demographic data, immature granulocyte count (IGC), delta neutrophil index (DNI), white blood cell (WBC) count, C-reactive protein (CRP), and albumin levels were recorded. Based on operative findings and histopathological examination, the patients were classified into 2 groups uncomplicated (group I) and complicated (e.g., perforation, gangrenous and emphysematous cholecystitis; group II) groups. The IBM SPSS version 26.0 (SPSS Corp, Armonk, NY, USA) was used to assess differences in blood parameters between groups. The predictive values of the parameters evaluated were estimated using ROC analysis. A p-value<0.05 was considered statistically significant. RESULTS: Acute complicated cholecystitis was found in 138 of 351 patients. No significant difference was detected in age and gender distribution between groups (p=0.352 and p=0.214, respectively). When blood parameters were assessed, it was found that IGC, DNI, WBC, and CAR values were significantly higher in group II (p<0.001; p<0.001, p<0.001, and p=0.036, respectively), while there was no significant difference in CRP and albumin between groups (p=0.099 and p=0.53, respectively). In the ROC analysis, the highest AUC value was found for IG count and DNI (0.784 and 0.775, respectively). The sensitivity and specificity were found as 68.8% and 86.9% for IG count and 49.3% and 96.2% for DNI, respectively. CONCLUSIONS: The IG count and DNI are two novel parameters with strong predictive value in the early diagnosis of acute complicated cholecystitis, which may support clinical findings, imaging studies, and other laboratory parameters.

The effect of procalcitonin and immature granulocyte ratio in predicting the development of acute necrotizing pancreatitis: evidence from 582 cases.

OBJECTIVE: Acute pancreatitis (AP) is one of the diseases that surgical clinics deal with the most. While mortality rates are approximately 1% in all cases, this rate may increase to 15% in pancreatic necrosis cases. Therefore, early diagnosis and treatment are very important in necrotizing pancreatitis. Our aim in this study is to present the guiding effectiveness of procalcitonin and immature granulocyte ratios (IG%) in planning the early diagnosis and treatment of acute necrotizing pancreatitis. PATIENTS AND METHODS: 582 patients hospitalized in our clinic with the diagnosis of acute pancreatitis were included in this study. All patients were divided into two groups as acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) according to tomography results. White blood cell (WBC) count, procalcitonin, IG%, C-reactive protein (CRP), amylase and lipase, albumin, CRP/albumin levels were recorded. The differences between the two groups were analyzed statistically. RESULTS: According to the results of contrast-enhanced abdominal tomography (CECT), 525 patients were diagnosed with AEP and 57 with ANP. WBC, CRP, procalcitonin, IG and CRP/albumin were found to be significantly higher in ANP patients when compared to AEP (p<0.0001). According to the ROC analysis result, procalcitonin (AUROC: 0.999), IG% (AUROC: 0.995), WBC count (AUROC: 0.841), CRP (AUROC: 0.947), albumin (AUROC: 0.862), and CRP/albumin (AUROC: 0.946) ratio were markers that could be used for early prediction of ANP. CONCLUSIONS: Early diagnosis of ANP can reduce morbidity and mortality. Procalcitonin and IG% levels can be easily accessible and effective markers in the early diagnosis of ANP and in the planning of treatment.

The Utility of Immature Granulocyte Count and Percentage on the Prediction of Acute Appendicitis in the Suspected Acute Appendicitis According to the Alvarado Scoring System: A Retrospective Cohort Study.

BACKGROUND: This study aimed to investigate the utility of immature granulocyte count and percentage on the prediction of suspected acute appendicitis according to the Alvarado scoring system and its effect on the need for computed tomography scanning. METHODS: Adult patients who had an Alvarado scoring system between 4 and 7 with the first imaging technique computed tomography were included and retrospectively analyzed. The immature granulocyte count and granulocyte percentage were obtained from the blood samples taken at the time of the patient's first admission to the hospital. RESULTS: A total of 652 patients were evaluated and 186 patients were included in the study. Acute appendicitis was not detected in computed tomography imaging of 121 (65%) patients (group N) and detected in 65 (35%) patients (group P). The mean immature granulocyte percentage in group N and group P were 0.314 ± 0.188 (0.00-1.40) and 0.364 ± 0.205 (0.05-1.00), respectively. The mean immature granulocyte percentage was similar between groups (P = .095). The mean immature granulocyte count was 33 ± 46/µL (0-50) in group N and 60 ± 85/µL (10-690) in group P. Immature granulocyte count was significantly higher in group P (P = .005). Univariate analysis results revealed that age and immature granulocyte percentage were not predictive factors for the presence of acute appen- dicitis in suspected cases (P > .05). On the other hand white blood cell, neutrophil-lymphocyte ratio, C-reactive protein, and immature granulocyte count were determined as predictive factors in univariate analysis and multivariate analysis. Receiver operating character- istic curve analysis of preoperative immature granulocyte percentage and immature granulocyte count values in the diagnosis of acute appendicitis: the cut-off value of immature granulocyte percentage was ≥0.35 and its sensitivity, specificity, positive predictive value, and negative predictive value were 44.1%, 72.1%, 71.1%, and 41.5%, respectively (area under the curve: 0.588; CI: 0.484-0.682). The cut-off value of immature granulocyte count was ≥35/µL and its sensitivity, specificity, positive predictive value, and negative predictive value were 66.1%, 73.6%, 71.9%, and 67.7%, respectively (area under the curve: 0.743; CI: 0.659-0.827) Conclusion: Immature granulocyte count is a predictive factor for acute appendicitis in patients with the middle-risk group according to the Alvarado score and may be useful for the selective use of tomography.

A specific esterase and pH logically regulate ESIPT: different kinds of granulocyte sorting.

Simultaneously detecting naphthol AS-D chloroacetate esterase (NAS-DCE) and pH is an effective way to separate different granulocytes, which is of great significance for the analysis of blood. A series of fluorescent small molecules (HBT-ASDs) were designed, whose ESIPT process could be logically regulated by NAS-DCE and pH. One typical molecule, HBT-ASD-2, emits three kinds of fluorescence output signal at 438 nm and 545 nm for NAS-DCE under different pH values (5.0, 7.4 and 10, respectively). According to such differential signals, the acid, neutrophil and alkaline granulocytes can be sorted, and the activity of NAS-DCE can also be simultaneously monitored in real-time. Thus, a simple analytical tool for clinical blood monitoring and analysis is provided.

Low-Density Granulocyte Contamination From Peripheral Blood Mononuclear Cells of Patients With Sepsis and How to Remove It - A Technical Report.

Elucidating the mechanisms contributing to the dysregulated host response to infection as part of the syndrome is a current challenge in sepsis research. Peripheral blood mononuclear cells are widely used in immunological studies. Density gradient centrifugation, a common method, is of limited use for blood drawn from patients with sepsis. A significant number of low-density granulocytes co-purify contributing to low purity of isolated peripheral blood mononuclear cells. Whole blood anticoagulated with lithium heparin was drawn from patients with sepsis (n=14) and healthy volunteers (n=11). Immediately after drawing, the plasma fraction was removed and PBMC were isolated from the cellular fraction by density gradient centrifugation. Samples derived from patients with sepsis were subsequently incubated with cluster of differentiation 15 MicroBeads and granulocytes were depleted using magnetic-activated cell sorting. Core cellular functions as antigen presentation and cytokine secretion were analyzed in cells isolated from healthy volunteers (n=3) before and after depletion to confirm consistent functionality. We report here that depleting CD15+ cells after density gradient centrifugation is a feasible way to get rid of the low-density granulocyte contamination. Afterwards, the purity of isolated, functionally intact peripheral blood mononuclear cells is comparable to healthy volunteers. Information on the isolation purity and identification of the containing cell types are necessary for good comparability between different studies. Depletion of CD15+ cells after density gradient centrifugation is an easy but highly efficient way to gain a higher quality and more reliability in studies using peripheral blood mononuclear cells from septic patients without affecting the functionality of the cells.

Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program.

Rationale: Some reports indicate longitudinal variability in sputum differential cell counts, whereas others describe stability. Highly variable sputum eosinophil percentages are associated with greater lung function loss than persistently elevated eosinophil percentages, but elevated neutrophils are linked to more severe asthma.Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics.Methods: The SARP III (Severe Asthma Research Program III) cohort underwent comprehensive phenotype characterization at baseline and annually over 3 years. Adult subjects with acceptable sputum levels were assigned to one of three longitudinal sputum groups: eosinophils predominantly <2%, eosinophils predominantly ≥2%, or highly variable eosinophil percentages (>2 SDs determined from independent, repeated baseline eosinophil percentages). Subjects were similarly assigned to one of three longitudinal neutrophil groups with a 50% cut point.Measurements and Main Results: The group with predominantly <2% sputum eosinophils had the highest lung function (prebronchodilator FEV1% predicted, P < 0.01; FEV1/FVC ratio, P < 0.001) at baseline and throughout 3 years compared with other eosinophil groups. Healthcare use did not differ, although the highly variable eosinophil group reported more asthma exacerbations at Year 3. Longitudinal neutrophil groups showed few differences. However, a combination of predominantly ≥2% eosinophil and ≥50% neutrophil groups resulted in the lowest prebronchodilator FEV1% predicted (P = 0.049) compared with the combination with predominantly <2% eosinophils and<50% neutrophils.Conclusions: Subjects with predominantly ≥2% sputum eosinophils in combination with predominantly ≥50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare use.

Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor.

Neutropenia and neutrophil dysfunction cause serious infections and inflammatory bowel disease in glycogen storage disease type Ib (GSD-Ib). Our discovery that accumulating 1,5-anhydroglucitol-6-phosphate (1,5AG6P) caused neutropenia in a glucose-6-phosphatase 3 (G6PC3)-deficient mouse model and in 2 rare diseases (GSD-Ib and G6PC3 deficiency) led us to repurpose the widely used antidiabetic drug empagliflozin, an inhibitor of the renal glucose cotransporter sodium glucose cotransporter 2 (SGLT2). Off-label use of empagliflozin in 4 GSD-Ib patients with incomplete response to granulocyte colony-stimulating factor (GCSF) treatment decreased serum 1,5AG and neutrophil 1,5AG6P levels within 1 month. Clinically, symptoms of frequent infections, mucosal lesions, and inflammatory bowel disease resolved, and no symptomatic hypoglycemia was observed. GCSF could be discontinued in 2 patients and tapered by 57% and 81%, respectively, in the other 2. The fluctuating neutrophil numbers in all patients were increased and stabilized. We further demonstrated improved neutrophil function: normal oxidative burst (in 3 of 3 patients tested), corrected protein glycosylation (2 of 2), and normal neutrophil chemotaxis (1 of 1), and bactericidal activity (1 of 1) under treatment. In summary, the glucose-lowering SGLT2 inhibitor empagliflozin, used for type 2 diabetes, was successfully repurposed for treating neutropenia and neutrophil dysfunction in the rare inherited metabolic disorder GSD-Ib without causing symptomatic hypoglycemia. We ascribe this to an improvement in neutrophil function resulting from the reduction of the intracellular concentration of 1,5AG6P.

[CD64 index as a marker of infection in patients with postoperative fever]. / El índice CD64 como marcador de infección en pacientes con fiebre postoperatoria.

OBJECTIVE: To evaluate the utility of the granulocyte CD64 index as a marker of infection in patients with postoperative fever. METHODS: Prospective observational study of a cohort of patients with postoperative fever (2nd-21st day after the intervention) collected during 14 months. Obtaining blood samples during the first 24 hours after the febrile peak to determine the CD64 index (ratio of fluorescence intensity, measured, in the granulocytes of the patient with respect to healthy controls), procalcitonin and C-reactive protein (CRP). RESULTS: During the study period, 50 patients were included, 28 patients (56%) with infection and 22 patients (44%) without evidence of infection. The PCR, procalcitonin and the CD64 index showed significantly higher values in the group of patients who suffered infection. The CD64 index showed a sensitivity of 88.9%, with a specificity of 65.2%. The positive predictive value (PPV) was 75% and the negative predictive value (NPV) was 83.3%, with an area under the curve (AUC) of 0.805 (95% CI 0.68-0.93). Procalcitonin presented a sensitivity of 53.9% and specificity of 86.4%, with NPV and PPV of 82.4% and 61.3% respectively, with AUC of 0.752 (95% CI 0.61-0.89). Regarding the PCR, it showed a sensitivity of 100%, with specificity of 4.4% with an area under the curve of 0.676 (95% CI 0.52-0.83). CONCLUSIONS: The quantification of the CD64 index in patients who develop fever in the early postoperative period is useful to distinguish post-surgical inflammatory phenomena from episodes of established infection.

Frontline Science: Elevated nuclear lamin A is permissive for granulocyte transendothelial migration but not for motility through collagen I barriers.

Transendothelial migration (TEM) of lymphocytes and neutrophils is associated with the ability of their deformable nuclei to displace endothelial cytoskeletal barriers. Lamin A is a key intermediate filament component of the nuclear lamina that is downregulated during granulopoiesis. When elevated, lamin A restricts nuclear squeezing through rigid confinements. To determine if the low lamin A expression by leukocyte nuclei is critical for their exceptional squeezing ability through endothelial barriers, we overexpressed this protein in granulocyte-like differentiated HL-60 cells. A 10-fold higher lamin A expression did not interfere with chemokinetic motility of these granulocytes on immobilized CXCL1. Furthermore, these lamin A high leukocytes exhibited normal chemotaxis toward CXCL1 determined in large pore transwell barriers, but poorly squeezed through 3 µm pores toward identical CXCL1 gradients. Strikingly, however, these leukocytes successfully completed paracellular TEM across inflamed endothelial monolayers under shear flow, albeit with a small delay in nuclear squeezing into their sub-endothelial pseudopodia. In contrast, CXCR2 mediated granulocyte motility through collagen I barriers was dramatically delayed by lamin A overexpression due to a failure of lamin A high nuclei to translocate into the pseudopodia of the granulocytes. Collectively, our data predict that leukocytes maintain a low lamin A content in their nuclear lamina in order to optimize squeezing through extracellular collagen barriers but can tolerate high lamin A content when crossing the highly adaptable barriers presented by the endothelial cytoskeleton.

Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies.

Current next-generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumors. Recent studies in myeloproliferative neoplasms have further demonstrated that, not only the mutational profile, but also the order in which these mutations are acquired is relevant for our understanding of the disease. Our ability to assign mutation order from NGS data alone is, however, limited. Here, we present a strategy of highly multiplexed genotyping of burst forming unit-erythroid colonies based on NGS results to assess subclonal tumor structure. This allowed for the generation of complex clonal hierarchies and determination of order of mutation acquisition far more accurately than was possible from NGS data alone.

Comprehensive analysis of circRNA expression profiles in humans by RAISE.

Circular RNAs (circRNAs) are pervasively expressed circles of non­coding RNAs. Even though many circRNAs have been reported in humans, their expression patterns and functions remain poorly understood. In this study, we employed a pipeline named RAISE to detect circRNAs in RNA­seq data. RAISE can fully characterize circRNA structure and abundance. We evaluated inter-individual variations in circRNA expression in humans by applying this pipeline to numerous non­poly(A)-selected RNA­seq data. We identified 59,128 circRNA candidates in 61 human liver samples, with almost no overlap in the circRNA of the recruited samples. Approximately 89% of the circRNAs were detected in one or two samples. In comparison, 10% of the linear mRNAs and non­coding RNAs were detected in each sample. We estimated the variation in other tissues, especially the circRNA high-abundance tissues, in advance. Only 0.5% of the 50,631 brain circRNA candidates were shared among the 30 recruited brain samples, which is similar to the proportion in liver. Moreover, we found inter- and intra-individual diversity in circRNAs expression in the granulocyte RNA­seq data from seven individuals sampled 3 times at one-month intervals. Our findings suggest that careful consideration of inter-individual diversity is required when extensively identifying human circRNAs or proposing their use as potential biomarkers and therapeutic targets in disease.

[ALLOCATION OF ZINC, MAGNESIUM AND COPPER IN GRANULOCYTES AND SERUM OF RABBITS WHILE INTRODUCTION OF SUBSTANCES THAT CHANGE THE FUNCTIONAL STATE OF ADRENAL CORTEX AND THE AUTONOMIC NERVOUS SYSTEM].

It was investigate the content of zinc, magnesium and copper in granulocytes and blood serum of the rabbits, that were injected with substances, that change the functional state of adrenal cortex, sympathetic-adrenal and parasympathetic nervous systems. It has been found that adrenaline, prednisolone and pilocarpine caused the multidirectional changes of these metals content in cells and in extracellular space. In this significant increase of zinc concentration by 33 - 42%, magnesium--by 33 -50%, and also decrease of copper content by 25-50% was observed in granulocytes of animals after adrenal hormones injections. Under the influence of cholinomimetics content of zinc and magnesium were essential decreased in granulocytes of the rabbits, by 58% and by 33% respectively, and content of copper was risen by 43% (P < 0.001). The opposite pattern was observed in serum. Adrenaline and prednisolone prescription caused a significant decrease of zinc concentration by 20-24%, magnesium--by 22-33%, and increase of copper content by 36-43%. Pilocarpine injection caused a decrease of zinc and magnesium content by 28 and 33% (P < 0.01) respectively, and an increase of copper concentration by 43% (P < 0.001). The obtained results also indicate a synergistic relationship between zinc and magnesium in cells, but antagonistic--these metals with copper.

Febrile ulceronecrotic Mucha-Habermann disease following suspected hemorrhagic chickenpox infection in a 20-month-old boy.

We present the youngest pediatric patient so far with febrile ulcerative Mucha-Haberman disease (FUMHD) after an admitting clinical picture of hemorrhagic varicella infection. With a time to diagnosis of 25 days, the 20-month-old boy responded to low dose cyclosporine and prednisolone given for 3 months and is free of disease after 4 years of follow up. We describe a polyclonal CD8+ T cell response with elevated pro-inflammatory cytokines and a fivefold upregulation of the high-affinity Fc receptor type I (CD64) on granulocytes. Early consideration of FUMHD in the differential diagnosis of a systemic inflammatory disease combined with a generalized necrotizing rash is important for early and adequate management of children with this rare and challenging disease.

The effect of sample storage on the Peroxidation of Leukocytes Index Ratio (PLIR) measure.

Delays in processing are frequent because of problems associated with transporting the samples to the laboratory. Thus, we aimed to evaluate the effect of sample storage on the Peroxidation of Leukocytes Index Ratio (PLIR). Differences between PLIR values of lymphocytes (PLIR-L), monocytes (PLIR-M) and granulocytes (PLIR-G) were observed in fresh samples. Sample storage affected the evaluation of PLIR. In particular, PLIR-L was lower in stored samples compared to fresh samples. In conclusion, our results suggest that fresh samples are recommended for assessing the PLIR.

Membrane and soluble Toll-like receptor 2 in patients with psoriasis treated by Goeckerman therapy.

BACKGROUND: Toll-like receptor (TLR) 2 belongs to the large TLR receptor family comprised of at least 10 members with different roles in innate immunity. Psoriasis is recognized as a T-cell driven immune-mediated systemic inflammatory disease with a skin manifestation. An effective therapeutic approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to assess both the kinetics of the expression of TLR2 on blood cells and the concentration of soluble (s)TLR2 in serum of patients with psoriasis and to examine the effect of GT on both TLR2 expression and sTLR2 level. METHODS: Both membrane and sTLR2 were determined in 20 patients and 20 healthy controls. sTLR2 was evaluated by enzyme-linked immunosorbent assay. Flow cytometry method was used to determine the expression of membrane TLR2 of monocytes and granulocytes. RESULTS: The serum level of sTLR2 was significantly lower (P < 0.0001) in patients both before and after GT compared to the control group. Compared to the membrane expression of TLR2 on monocytes of healthy blood donors, TLR2 expression was significantly higher in patients both before and after GT (P = 0.0001). Similarly, TLR2 expression on granulocytes was significantly higher in patients both before (P = 0.0061) and after (P < 0.0001) therapy than in control. CONCLUSIONS: Membrane and soluble TLR2 may be involved in the pathogenesis of psoriasis. Both remained unchanged by GT.

ID2 and ID3 protein expression mirrors granulopoietic maturation and discriminates between acute leukemia subtypes.

The inhibitors of DNA binding (ID) inhibit basic helix-loop-helix transcription factors and thereby guide cellular differentiation and proliferation. To elucidate the involvement of IDs in hematopoiesis and acute leukemias (AL), we analyzed ID2 and ID3 expression in hematopoiesis and leukemic blasts in bone marrow biopsies (BMB). BMB of healthy stem cell donors (n = 19) and BMB of patients with acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MD; n = 19), de novo AML (n = 20), B-acute lymphoblastic leukemia (B-ALL) (n = 23), T-ALL (n = 19), were immunohistochemically stained for ID2 and ID3 expression. The expression patterns were evaluated and quantified for each hematopoietic lineage and each leukemia subtype. In normal BMB, immature granulopoiesis showed weak ID2 and strong ID3 expression, which was lost during maturation (p < 0.001). Erythropoiesis remained negative for ID2/3 (p < 0.001). ID2/3 expression differed between immature granulopoiesis and leukemic blasts (p < 0.001). Moreover, differential ID2/3 expression was seen between AL subgroups: AML, especially AML-MD, had more ID2- (p < 0.001) and ID3-positive (p < 0.001) blasts than ALL. We show a comprehensive in situ picture of ID2/3 expression in hematopoiesis and AL. Morphologically, ID2/3 proteins seem to be involved in the granulopoietic maturation. Importantly, the distinct ID2/3 expression patterns in AL indicate a specific deregulation of ID2/3 in the various types of AL and may support subtyping of AL.

Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery.

BACKGROUND: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects, and n-3 FA supplements may improve outcome after surgery. METHODS: In a randomized double-blind placebo-controlled trial in single centre, patients referred for elective colorectal cancer surgery received either an n-3 FA-enriched oral nutritional supplement (ONS) (Supportan, 200 ml twice daily) providing 2.0 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA) per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7 days after surgery. The primary endpoint was infectious and non-infectious complications within 30 days of surgery. Secondary endpoints were length of hospital stay, intensive care unit admission, readmissions, and concentrations of marine n-3 FAs and arachidonic acid in granulocyte membranes. RESULTS: Some 148 consecutive patients (68 women, 80 men; mean age 71 (range 41-89) years) were randomized. There was no significant difference between groups in infectious or non-infectious postoperative complications (P = 1.000). Granulocyte levels of EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA-enriched supplement group compared with the control group (P < 0.001). The arachidonic acid level in granulocytes was significantly lower in the enriched group than in the control group (P < 0.001). CONCLUSION: EPA, DHA and DPA were incorporated into granulocytes in patients receiving n-3 FAs, but this was not associated with improved postoperative outcomes. REGISTRATION NUMBER: NCT00488904 (http://www.clinicaltrials.gov).