Associations of CBC-Derived inflammatory indicators with sarcopenia and mortality in adults: evidence from Nhanes 1999 ∼ 2006.

BACKGROUND: It has been proposed that inflammation plays a role in the development of sarcopenia. This study aimed to investigate the links of complete blood cell count (CBC) parameters and CBC-derived inflammatory indicators with sarcopenia and mortality. METHODS: Data pertaining to sarcopenia were extracted from the 1999-2006 National Health and Nutrition Examination Survey (NHANES), and mortality events were ascertained through the National Death Index up to December 31, 2019. The CBC-derived inflammatory indicators assessed in this study included the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII). The prognostic significance of these CBC-derived inflammatory indicators was evaluated using the random survival forests (RSF) analysis. RESULTS: The study encompassed a cohort of 12,689 individuals, among whom 1,725 were diagnosed with sarcopenia. Among individuals with sarcopenia, 782 experienced all-cause mortality, and 195 succumbed to cardiovascular causes. Following adjustment for confounding variables, it was observed that elevated levels of NLR, dNLR, NMLR, SIRI, and SII were associated with an increased prevalence of sarcopenia. Among participants with sarcopenia, those in the highest quartile of NLR (HR = 1.336 [1.095-1.631]), dNLR (HR = 1.274 [1.046-1.550]), MLR (HR = 1.619 [1.290-2.032]), NMLR (HR = 1.390 [1.132-1.707]), and SIRI (HR = 1.501 [1.210-1.862]) exhibited an elevated risk of all-cause mortality compared to those in the lowest quartile of these inflammation-derived indicators. These associations were similarly observed in cardiovascular mortality (HR = 1.874 [1.169-3.003] for MLR, HR = 1.838 [1.175-2.878] for SIRI). The RSF analysis indicated that MLR exhibited the highest predictive power for both all-cause and cardiovascular mortality among individuals with sarcopenia. CONCLUSIONS: Our findings underscore the association between CBC-derived inflammatory indicators and mortality in adults with sarcopenia. Of note, MLR emerged as the most robust predictor of all-cause and cardiovascular mortality in this population.

Trends in Management of Simple Febrile Seizures at US Children's Hospitals.

OBJECTIVE: We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS: In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS: We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS: Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.

Trends Over Time in Use of Nonrecommended Tests and Treatments Since Publication of the American Academy of Pediatrics Bronchiolitis Guideline.

Importance: Acute viral bronchiolitis is a common and costly pediatric condition for which clinical practice guidelines discourage use of diagnostic tests and therapies. Objective: To evaluate trends over time for use of nonrecommended services for bronchiolitis since publication of the American Academy of Pediatrics clinical practice guideline on bronchiolitis (originally published in October 2006 and updated in November 2014). Design, Setting, and Participants: This cohort study was conducted using interrupted time-series regression analysis adjusting for the hospital providing service, patient demographic characteristics, and payer, with 2014 guideline update publication as the event point. Included patients were children younger than 2 years old discharged from the emergency department (ED) or hospital inpatient setting with a primary diagnosis of bronchiolitis at US Children's Hospitals contributing data to the Pediatric Health Information Systems database. Data were analyzed from June through December 2020. Main Outcomes and Measures: Rates of nonrecommended tests (ie, chest radiography, viral testing, and complete blood cell count) and treatments (ie, bronchodilators, corticosteroids, antibiotics) were measured. Results: Among 602 375 encounters involving children with a primary diagnosis of bronchiolitis, 404 203 encounters (67.1%) were ED discharges and 198 172 encounters (32.9%) were inpatient discharges; 468 226 encounters (77.7%) involved children younger than 12 months, and 356 796 encounters (59.2%) involved boys. In the period after initial guideline publication (ie, November 2006 to November 2014), a negative use trajectory was found in all measures except viral testing in the ED group. Using the 2014 guideline update as the event point, several measures showed decreased use between study time periods. The greatest decrease was in bronchodilator use, which changed by -13.5 percentage points in the ED group (95% CI, -15.2 percentage points to -11.8 percentage points) and -11.3 percentage points in the inpatient group (95% CI, -13.1 percentage points to -9.4 percentage points). In the period after the 2014 guideline update (ie, December 2014 to December 2019), bronchodilators also showed the greatest change in usage trajectory, steepening more than 2-fold in both groups. In the ED group, the negative trajectory steepened from -0.11% monthly (95% CI, -0.13% to -0.09%) in the first guideline period to a new mean monthly slope of -0.26% (95% CI, -0.30% to -0.23%). In the inpatient group, the mean monthly slope steepened from -0.08% (95% CI, -0.10 to -0.05%) to -0.26% (95% CI, 0.30% to -0.22%). Length of stay decreased from 2.0 days (95% CI, 1.9 days to 2.1 days) to 1.7 days (95% CI, 1.7 days to 1.8 days). Hospital admission rate decreased from 18.0% (95% CI, 13.8% to 22.2%) to 17.8% (95% CI, 13.6 to 22.1%). Conclusions and Relevance: This cohort study with interrupted time-series analysis found that use of most nonrecommended bronchiolitis services decreased continuously after 2006. The rate of decline in bronchodilator use increased more than 2-fold after the 2014 guideline update. These findings support potential associations of practice guidelines with improved bronchiolitis care.

Association of bone mineral density with peripheral blood cell counts and hemoglobin in Chinese postmenopausal women: A retrospective study.

Osteoporosis (OP) is a metabolic bone disease that can cause structural changes in bone marrow cavity. Bone marrow is the hematopoietic organ of adults. Accumulating evidence has shown a close connection between bone marrow hematopoietic function and bone formation. Some studies have revealed that OP is associated with hematopoiesis. However, the relationship is not definite.This study aimed to evaluate the association between peripheral blood cell counts (white blood cells [WBC], red blood cells [RBC], platelets [PLT]), hemoglobin [HGB], and bone mineral density [BMD]) in a sample of Chinese postmenopausal women. This is a retrospective study involving 673 postmenopausal women cases. The BMD of lumbar spine and left hip joint were measured by dual-energy X-ray absorptiometry. The levels of blood cell counts and HGB were measured and analyzed.The study results showed the WBC, RBC, PLT, and HGB levels of postmenopausal women in the OP group were all higher than those in the non-osteoporosis group. Spearman linear trend analysis and partial correlation analysis demonstrated that BMD was negatively correlated with WBC, RBC, PLT, and HGB in postmenopausal women.Due to the differences between different countries and races, and there are few studies on the association of BMD with peripheral blood cell counts and HGB in Chinese Postmenopausal Women. Therefore, more large sample studies are needed.

Hematological indices as indicators of silent inflammation in achalasia patients: A cross-sectional study.

Complete blood count (CBC)-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte (ELR) ratio, and platelet-to-lymphocyte ratio (PLR) are sensitive markers of occult inflammation and disease activity for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, esophageal cancer, etc. We assessed NLR, PLR, MLR, and ELR as indicators of inflammation in achalasia patients.This cross-sectional study included 103 achalasia patients and 500 healthy blood donor volunteers (HD). Demographic, clinical and laboratory information was collected. NLR, MLR, ELR and PLR were calculated. Peripheral Th22, Th17, Th2 and Th1 subsets were determined by flow cytometry. Correlation between hematologic indices and clinical questionnaires scores, HRM parameters and CD4+ T-cells were assessed. Hematologic parameters associated with the different achalasia subtypes were evaluated by logistic regression analysis.Hemoglobin, leukocytes, lymphocytes, monocytes, and platelets counts were significantly lower in achalasia patients vs controls. NLR (P = .006) and ELR (P < .05) were higher in achalasia patients vs controls. NLR was significantly associated with achalasia in multivariate analysis (P < .001). Compared to HD, the achalasia group was 1.804 times more likely to have higher NLR (95% CI 1.287-2.59; P < .001). GERD-HRQL score had statistically significant correlations with PLR (Pearson's rho:0.318, P = .003), and ELR (Pearson's rho:0.216; P = .044). No correlation between CD4+ T-cells and hematologic indices were determined. NLR with a cut-off value of ≥2.20 and area under the curve of 0.581 yielded a specificity of 80% and sensitivity of 40%, for the diagnosis of achalasia.NLR is increased in achalasia patients vs HD. Sensitivity and specificity achieved by NLR may contribute to a clinical and manometric evaluation. We suggest these indices as potential indicators of silent inflammation and disease activity.

The clinical utility and adverse consequences of the complete blood count in an internal medicine department.

The clinical utility and adverse consequences of the admission and follow-up complete blood count (CBC) in hospitalised patients are unclear. We selected 273 patients chosen from a single internal medicine department. To determine clinical utility and adverse consequences, we interviewed attending physicians and reviewed patients' charts. There were 12 (4.4%) patients hospitalised because of the CBC test result, six referred appropriately with a low haemoglobin concentration found in outpatient clinics and six (2.2%) patients (95% confidence interval 0.8-4.7%) inappropriately hospitalised because of incidental findings. In the hospital, according to the physicians, nearly all treatment changes made were for blood transfusions that were not indicated in 18 (6.6%) patients (95% confidence interval 4.0-10.2%). The only unexpected findings were in four patients with an indication for a blood transfusion admitted with an acute coronary syndrome and haemoglobin values 8-9.9 g/dL, and in one bedridden patient with dementia with acute myeloid leukaemia. There were 290 follow-up CBC tests not resulting in differential treatment. We conclude that admission CBC tests commonly lead to adverse consequences, due to physician errors in judgement. Incidental findings of anaemia justify CBC testing in patients with an acute coronary event. The rare patient with an incidental finding resulting in appropriate differential treatment might justify non-selective admission CBC counts, if physician education reduces the rate of inappropriate blood transfusions.

Clustered interventions to reduce inappropriate duplicate laboratory tests in an Irish tertiary hospital.

BACKGROUND: There is increasing emphasis on understanding the rate, and avoidable costs, of inappropriate laboratory testing in hospitals, especially associated with duplication of tests following transfer of patients from one hospital to another. While studies of inappropriate testing have been reported previously, there are no published data relevant to Ireland. AIMS: To determine the baseline rate of inappropriate testing for a subset of clinical parameters, specifically, full blood counts (FBC), biochemistry profiles (Bio) and coagulation (Coag) screens for geriatric patients transferring to and from University Hospital Limerick (UHL). Prospective pilot-scale implementation of five clustered interventions, and assessment of their effect. METHODS: Baseline testing levels were determined between October 2013 and January 2014. A patient survey was conducted to evaluate patient awareness of the blood tests they underwent. Five interventions were trialed sequentially each month between January and May 2014. These included: educational poster, intern training, presentations and communication to consultants; automated prompt in the Lab Information Technology system; highlighting of patient survey results to medical staff; inclusion of laboratory test details on patient transfer document; patient booklet promoting empowerment. Impact was assessed by determining rates of inappropriate laboratory testing monthly, and associated actual cost reductions were calculated. RESULTS: Approximately two-thirds of geriatric inpatients were unaware of why they underwent blood tests. Baseline numbers of inappropriate duplicate FBCs, Bio profiles and Coag tests were 758, 749 and 268 respectively for patients transferring to and from UHL. Following the interventions, these numbers dropped to 85, 84 and 0, respectively. CONCLUSION: The interventions resulted in sustained reduction in rates of inappropriate testing by May 2014. Extrapolated cost reductions exceed two million Euro annually. The most effective intervention involved staff education.

Pharmacology of Thiopurine Therapy in Inflammatory Bowel Disease and Complete Blood Cell Count Outcomes: A 5-Year Database Study.

BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites. METHODS: The authors scrutinized the therapeutic drug monitoring database of the VU University medical center and subsequently merged this database with the Clinical Laboratory database of our hospital covering the same time period (2010-2015). RESULTS: The authors included 940 laboratory findings of 424 unique patients in this study. Concentrations of 6-thioguanine nucleotides (6-TGN) correlated negatively with red blood cell count, white blood cell count, and neutrophil count in both azathioprine (AZA) and mercaptopurine users. There was a positive correlation with mean corpuscular volume. In patients using 6-thioguanine, 6-TGN concentrations correlated positively with white blood cell count. Furthermore, there was an inverse correlation between patient's age and 6-TGN concentrations in patients using AZA or 6-thioguanine, and we observed an inverse correlation between body mass index and 6-TGN concentrations in patients using AZA or mercaptopurine. No relations were observed with liver test abnormalities. CONCLUSIONS: Thiopurine derivative therapy influenced bone marrow production and the size of red blood cells. Age and body mass index were important pharmacokinetic factors in the generation of 6-TGN.

Development, history, and future of automated cell counters.

Modern automated hematology instruments use either optical methods (light scatter), impedance-based methods based on the Coulter principle (changes in electrical current induced by blood cells flowing through an electrically charged opening), or a combination of both optical and impedance-based methods. Progressive improvement in these instruments has allowed the enumeration and evaluation of blood cells with great accuracy, precision, and speed at very low cost. Future directions of hematology instrumentation include the addition of new parameters and the development of point-of-care instrumentation. In the future, in-vivo analysis of blood cells may allow noninvasive and near-continuous measurements.

Analysis of bone marrow aspiration fluid using automated blood cell counters.

Cytomorphological examination of aspirate smears remains the basic method to diagnose hematologic disorders and to evaluate treatment-related changes. Last-generation hematological analyzers can count, besides cells normally circulating in peripheral blood, some types of immature and abnormal cells, such as erythroblasts and immature granulocytes. The complex nature of bone marrow fluid, however, has prevented until now the routine utilization of blood cell counters in this area. Recent studies have shown the possibility of using bone marrow fluid as a substitute for peripheral blood for clinical tests in particular situations and for repetitive cytologic examinations in specific clinical and research fields.

Quality control of automated cell counters.

The hematology analyzers of today provide more reproducible analyses compared with those of a few decades ago, necessitating an evolution in hematology quality practices. The improved performance allows use of simple quality control rules. This improved performance also renders the repeat analysis of critical value specimens non value added. Some of the patient averaging techniques have become outmoded and need to be replaced by less complicated calculations but with truncation of predictable outlying populations. The ready availability of comparative peer quality control values helps to improve analyzer precision and accuracy, and simplifies instrument validation and calibration.

Novel parameters in blood cell counters.

Many modern automated cell counters offer novel parameters. Some of these, such as the CHr, reticulocyte hemoglobin equivalent, or immature platelet fraction, schistocytes have been accepted by many clinicians; the CHr has even become part of clinical practice guidelines for dialysis patients. Other parameters are still research-use only and lack well-defined reference ranges. One important albeit rare clinical problem is to characterize platelet volume in case of inherited thrombocytopenia. Most novel parameters are specific for certain instrument platforms, and results of even similar parameters from different manufacturers are often difficult to compare.

Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count.

BACKGROUND: 22q11.2 deletion syndrome is common affecting nearly 1 in 3000, including many with DiGeorge Syndrome and 5% of individuals with congenital heart disease. Diagnosis is important because affected patients have impaired immune function and may suffer high mortality rates if given non-irradiated blood products from graft versus host disease. Symptomatic hypocalcaemia may also occur. Our objective was to determine whether mean platelet volume (MPV), available from the routine full blood count, may be a useful and rapid indicator of 22q11.2 deletion. METHOD: A retrospective case control cohort study analysing MPV and 22q11.2 deletion status was performed in a paediatric population (n = 166) undergoing cardiac surgery between 1999 and 2005. RESULTS: Twenty children were 22q11.2 positive. The median MPV was significantly larger for the 22q11.2 positive patient group compared to the non-22q11.2 patients (10.9fL versus 8.6fL, p<0.001). The area under the curve of the receiver operating characteristics (ROC) curve of MPV was large enough (0.85) to enable the accurate prediction of 22q11.2 deletion using MPV. CONCLUSIONS: MPV is a useful screening test, involving no extra laboratory work, cost or patient discomfort. MPV>10fL is a positive predictor of the presence of 22q11.2 deletion in children with congenital heart disease (specificity 89.7%). This finding should aid rapid decision-making for ordering irradiated blood products to prevent potentially fatal transfusion-associated graft versus host disease. It will alert clinicians to monitor serum calcium levels closely to prevent hypocalcaemic seizures.

[Development of blood cell measurement].

Automated blood cell analyzers used in hematology laboratories are required to measure many specimens rapidly and efficiency has been realized through increasing the measurement parameters and throughput volume in one instrument. In the period of 1950's through the early part of 1960's, only red blood cells and white blood cells could be counted. In 1965, Technicon Corporation developed an instrument which can measure the number of blood cells, hemoglobin, hematocrit and calculate corpuscular constants simultaneously. Thereafter, the methodologies for simultaneous platelet measurement and precise determination of blood cell distribution have been developed. Then, the development of new reagents has achieved three part differentials in the distribution of white blood cells. Thanks to this development, microscopic white blood cell differentials has been replaced by blood cell analyzers in screening tests. Though blood cell analyzers may be further improved by expanding of the number of parameters available for simultaneous measurements, meeting social needs in the new era will not be possible without the creation and realization of new concepts employing new technologies such as IT (Information Technology).