Blood cell differential count discretisation modelling to predict survival in adults reporting to the emergency room: a retrospective cohort study.

OBJECTIVES: To assess the survival predictivity of baseline blood cell differential count (BCDC), discretised according to two different methods, in adults visiting an emergency room (ER) for illness or trauma over 1 year. DESIGN: Retrospective cohort study of hospital records. SETTING: Tertiary care public hospital in northern Italy. PARTICIPANTS: 11 052 patients aged >18 years, consecutively admitted to the ER in 1 year, and for whom BCDC collection was indicated by ER medical staff at first presentation. PRIMARY OUTCOME: Survival was the referral outcome for explorative model development. Automated BCDC analysis at baseline assessed haemoglobin, mean cell volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), platelet haematocrit (PCT), absolute red blood cells, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets. Discretisation cut-offs were defined by benchmark and tailored methods. Benchmark cut-offs were stated based on laboratory reference values (Clinical and Laboratory Standards Institute). Tailored cut-offs for linear, sigmoid-shaped and U-shaped distributed variables were discretised by maximally selected rank statistics and by optimal-equal HR, respectively. Explanatory variables (age, gender, ER admission during SARS-CoV2 surges and in-hospital admission) were analysed using Cox multivariable regression. Receiver operating curves were drawn by summing the Cox-significant variables for each method. RESULTS: Of 11 052 patients (median age 67 years, IQR 51-81, 48% female), 59% (n=6489) were discharged and 41% (n=4563) were admitted to the hospital. After a 306-day median follow-up (IQR 208-417 days), 9455 (86%) patients were alive and 1597 (14%) deceased. Increased HRs were associated with age >73 years (HR=4.6, 95% CI=4.0 to 5.2), in-hospital admission (HR=2.2, 95% CI=1.9 to 2.4), ER admission during SARS-CoV2 surges (Wave I: HR=1.7, 95% CI=1.5 to 1.9; Wave II: HR=1.2, 95% CI=1.0 to 1.3). Gender, haemoglobin, MCV, RDW, PDW, neutrophils, lymphocytes and eosinophil counts were significant overall. Benchmark-BCDC model included basophils and platelet count (area under the ROC (AUROC) 0.74). Tailored-BCDC model included monocyte counts and PCT (AUROC 0.79). CONCLUSIONS: Baseline discretised BCDC provides meaningful insight regarding ER patients' survival.

Use of the reticulocyte channel warmed to 41 °C of the XN-9000 analyzer in samples with the presence of cold agglutinins

ABSTRACT Objectives The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) < 370 g/L and in samples with the MCHC > 370 g/L, in the presence of cold agglutinins. Methods In this study, 60 blood samples (group 1) with the MCHC < 370 g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC > 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

Eosinopenia is a reliable marker of severe disease and unfavourable outcome in patients with COVID-19 pneumonia.

BACKGROUND AND AIM: Viral pneumonia is the most relevant clinical presentation of COVID-19 which may lead to severe acute respiratory syndrome and even death. Eosinopenia was often noticed in patients with COVID-19 pneumonia, but its role is poorly investigated. The aim of the present study was to investigate the characteristics and clinical outcomes of patients with COVID-19 pneumonia and eosinopenia. METHODS: We revised the records of consecutive patients with COVID-19 pneumonia admitted to our ER-COVID-19 area in order to compare clinical characteristics and outcomes of patients with and without eosinopenia. We considered the following clinical outcomes: 4-weeks survival; need for intensive respiratory support; and hospital discharge. RESULTS: Out of first 107 consecutive patients with pneumonia and a positive COVID-19 nasopharyngeal swab, 75 patients showed undetectable eosinophil count (absolute eosinopenia). At 4 weeks, 38 patients (38.4%) had required intensive respiratory treatment, 25 (23.4%) deceased and 42 (39.2%) were discharged. Compared with patients without absolute eosinopenia, patients with absolute eosinopenia showed higher need of intensive respiratory treatment (49.3% vs 13.3%, P < .001), higher mortality (30.6% vs 6.2%, P .006) and lower rate of hospital discharge (28% vs 65.6%, P < .001). Binary logistic regression analyses including neutrophil, lymphocyte, eosinophil, basophil and monocyte counts showed that absolute eosinopenia was an independent factor associated with 4-weeks mortality, need for intensive respiratory support and hospital discharge. CONCLUSIONS: Absolute eosinopenia is associated with clinical outcomes in patients with COVID-19 pneumonia and might be used as a marker to discriminate patients with unfavourable prognosis.

Use of the reticulocyte channel warmed to 41°C of the XN-9000 analyzer in samples with the presence of cold agglutinins.

OBJECTIVES: The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41°C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC)<370g/L and in samples with the MCHC>370g/L, in the presence of cold agglutinins. METHODS: In this study, 60 blood samples (group 1) with the MCHC<370g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC>370g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). RESULTS: The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. CONCLUSIONS: The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370g/L.

Preliminary assessment of the new Sysmex XN parameter Iron-Def for identifying iron deficiency.

BACKGROUND: Although the clinical assessment of iron status is usually based on iron stores, a rapid and accurate diagnosis of iron deficiency is challenging since ferritin is often unavailable as an urgent test and its value is frequently increased in acute phase conditions. This study was therefore aimed at evaluating the diagnostic performance of the new Sysmex XN "Iron Deficiency?" (Iron-Def) parameter for identifying patients with iron deficiency. MATERIALS AND METHODS: The study population consisted of 688 consecutive patients (median age: 71 years; 341 women and 347 men), referred for routine diagnostics to the Laboratory of Clinical Pathology of Lecco Hospital, Italy. A complete clinical chemistry profile and haematological testing were performed for identifying iron deficiency anaemia. RESULTS: A significant negative correlation was found between Sysmex XN Iron-Def and ferritin, serum iron, mean cell haemoglobin concentration, mean cell haemoglobin, mean corpuscular volume and age, while a positive correlation was noted with transferrin, percentage of microcytic red cell, red blood cell count and red blood cell distribution width. The diagnostic accuracy of Iron-Def for identifying patients with a percentage of saturation of transferrin <15% (n=104) was 84%, with a sensitivity of 0.952 and specificity of 0.538. A sub-analysis of 71 patients with ferritin <20 ng/dL yielded an even better diagnostic performance (86%, with a sensitivity of 0.935 and specificity of 0.620). DISCUSSION: Although additional confirmatory investigations would be needed, the preliminary findings of our study attest that Iron-Def may be an easy, inexpensive, rapid and reliable parameter for screening iron deficiency anaemia.

Prognostic nutritional index as a prognostic marker in glioblastoma: Data from a cohort of 282 Italian patients.

Preoperative prognostic nutritional index (PNI) is linked to the clinical outcome of patients with malignant tumours, however few studies have investigated its utility in predicting outcome in glioblastoma multiforme (GBM). We performed a retrospective study on adult patients with GBM in order to evaluate the impact of PNI on overall survival (OS), after adjusting for known prognostic factor (age, extent of surgery, Karnofsky performance status, radiochemotherapy). This is an Italian, multicentre, retrospective, cohort study. The patient's cohort includes 282 individuals with a newly diagnosed GBM followed in 3 Lombardia Hospitals In all cases the diagnosis was supported by histological data. Patient's information including sex, age at onset, Karnofsky performance status (KPS), extension of surgical resection (EOR), adjuvant treatment, antiepileptic treatment, serum variables and survival data were collected. Univariate and multivariate analysis did not reveal an association between PNI and overall survival in our series of GBM patients. PNI is a controversial marker for prognosis in GBM patients and further prospective studies are necessary to elucidate its role.

EEG and granular osmiophilic elements in early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare genetic disorder mainly attributable to a mutation in the presenilin 1 (PSEN1) gene. Clinical profile and instrumental findings share common features with adult neuronal ceroid lipofuscinosis. We documented the clinical course in EOAD patients bearing mutations in PSEN1. Genetic screening for dementia, EEG acquisition and determination of granular osmiophilic elements (GRODs) from skin biopsy were performed in a patient suffering from a severe cognitive decline and visual hallucinations. The pathogenic M146I mutation in PSEN1, and instrumental findings common to adult neuronal ceroid lipofuscinosis were found in the same patient. Posterior low pseudoperiodic sequences at EEG and GRODS elements at skin biopsy might constitute a signature in EOAD.

Antimicrobial resistance among Escherichia coli that cause childhood community-acquired urinary tract infections in Northern Italy.

BACKGROUND: Resistance rate of Escherichia coli against antimicrobials that are commonly prescribed in pediatric urinary tract infections is currently a matter of concern. METHODS: The antimicrobial susceptibility patterns of uropathogenic Escherichia coli strains to the common antibimcrobials ampicillin, cotrimoxazole, coamoxyclav, ceftazidime, ceftriaxone, nitrofurantoin, and gentamycin were determined in 177 children aged from 2 to 36 months. They presented with their first symptomatic community acquired urinary tract infection at the Department of Pediatrics, San Leopoldo Mandic Hospital, Merate-Lecco. RESULTS: High rates of ampicillin (inpatients: 50%; outpatients: 52%) resistance were identified. The resistance for cotrimoxazole (inpatients: 22%; outpatients: 15%) and especially coamoxyclav (inpatients: 6%; outpatients: 10%) was less pronounced than that to ampicillin. No resistance or less than 1% of resistance was identified for ceftazidime, ceftriaxone, nitrofurantoin, and gentamycin both in inpatients and in outpatients. CONCLUSIONS: Italian children affected with a community acquired urinary tract infection are initially managed orally with coamoxyclav or parenterally with ceftriaxone. The results of the present retrospective analysis support this attitude. Parenteral ceftriaxone or an aminoglycoside should be considered for patients on antimicrobial prophylaxis or recently prescribed antimicrobials.

Motor cortex changes in spinal cord injury: a TMS study.

Using paired pulse transcranial magnetic stimulation (TMS) paradigms, we studied cortical excitability in a patient with spinal cord lesion. During posterior tibial nerve stimulation, the contextual flexion of hand fingers contralateral to the stimulated lower limb had suggested a change in motor cortex excitability. Results showed a decrease in the activity of motor cortex inhibitory circuits. This could suggest that in spinal cord injury, just as in stroke and peripheral deafferentation, a disinhibition of latent synapses within the motor cortex and the rewriting of a new motor map can occur.

Abnormal fronto-parietal coupling of brain rhythms in mild Alzheimer's disease: a multicentric EEG study.

Cholinergic deafferentation/recovery in rats mainly impinges on the fronto-parietal coupling of brain rhythms [D. P. Holschneider et al. (1999) Exp. Brain Res., 126, 270-280]. Is this reflected by the functional coupling of fronto-parietal cortical rhythms at an early stage of Alzheimer's disease (mild AD)? Resting electroencephalographic (EEG) rhythms were studied in 82 patients with mild AD and in control subjects, such as 41 normal elderly (Nold) subjects and 25 patients with vascular dementia (VaD). Patients with AD and VaD had similar mini-mental state evaluation scores of 17-24. The functional coupling was estimated by means of the synchronization likelihood (SL) of the EEG data at electrode pairs, accounting for linear and non-linear components of that coupling. Cortical rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha (1 8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-40 Hz). A preliminary data analysis (Nold) showed that surface Laplacian transformation of the EEG data reduced the values of SL, possibly because of the reduction of influences due to head volume conduction. Therefore, the final analysis was performed on Laplacian-transformed EEG data. The SL was dominant at alpha 1 band in all groups. Compared with the Nold subjects, patients with VaD and mild AD presented a marked reduction of SL at both fronto-parietal (delta-alpha) and inter-hemispherical (delta-beta) electrode pairs. The feature distinguishing the patients with mild AD with respect to patients with VaD groups was a more prominent reduction of fronto-parietal alpha 1 SL. These results suggest that mild AD is characterized by an abnormal fronto-parietal coupling of the dominant human cortical rhythm at 8-10.5 Hz.

Activity-dependent modulation of synaptic transmission in the intact human motor cortex revealed with transcranial magnetic stimulation.

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.