Red cell distribution width is a potential predictor of early relapse in polymyalgia rheumatica.

Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p<0.03). In a stepwise logistic regression, RDW (p=0.01) predicted the risk of relapse at 6 months, while age, gender, CRP, ESR, Hb, MCV and prednisone dose did not fit the model. Our results show that RDW is an independent biomarker of early relapse, making this parameter a potentially promising predictive marker in PMR.

Association between red cell distribution width and response to methotrexate in rheumatoid arthritis.

Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p<0.0001). The increase of RDW was greater among patients with good EULAR response, becoming progressively smaller in cases with moderate and poor response (1.0% [0.4-1.4] vs. 0.7 [0.1-2.0] vs. 0.3 [-0.1-0.8]; p=0.03). RDW is a strong predictor of early response to MTX in RA. RDW significantly increases after MTX initiation in parallel to treatment response, suggesting a role as a marker of MTX effectiveness.

Efficacy of a galactogogue containing silymarin-phosphatidylserine and galega in mothers of preterm infants: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Human milk (HM) is the best possible food for all infants, especially for preterm ones, but lactation and breastfeeding are very difficult for mothers of preterm babies and high rates of breastfeeding difficulties have been reported. Our aim was to investigate the efficacy of a galactogogue containing silymarin-phosphatidylserine and galega in increasing milk production during the first month after delivery in a population of mothers of preterm infants. SUBJECTS/METHODS: Mothers of infants with gestational age (GA) between 27+0 and 32+6 weeks were enrolled in this prospective, double-blind, randomized trial and were randomly allocated to receive either the galactogogue containing silymarin-phosphatidylserine and galega, 5 g/day (galactogogue group, GG), or a placebo, 5 g of lactose per day (placebo group, PG) from the 3rd to the 28th day after delivery. RESULTS: Fifty mothers were included in each group. General characteristics of mothers and pregnancies were similar. Milk production was significantly greater in the GG at the 7th day of life and at the 30th day of life. Daily milk production from the 7th to the 30th day of life was 200 (110-380) ml in the GG vs 115 (60-245) ml in the PG (P<0.0001). The total production of milk during the study period was significantly higher in the GG (6523±5298 ml vs 4136±4093 ml; P<0.02). At the end of the study, 45 mothers of the GG were able to reach the target of milk supply of 200 ml/day compared with 25 mothers of the PG (P<0.01). No adverse reactions were noticed in the study groups. CONCLUSIONS: Silymarin-phosphatidylserine and galega increased milk production in mothers of preterm infants without any significant side effects.

Target fraction of inspired oxygen during open lung strategy in neonatal high frequency oscillatory ventilation: a retrospective study.

BACKGROUND: There is no agreement to define the target FiO2 to adopt in the lung recruitment phase during HFOV in preterm infants. We report our experience of an optimal lung volume strategy (OLVS), defined as FiO2≤0.25 during the recruitment phase, in a cohort of neonates with gestational age (GA) ≤27 weeks treated with elective HFOV for respiratory distress syndrome (RDS) between July 2006 and September 2008. METHODS: FiO2 used during the recruitment phase was different according to physician' evaluation. 51 newborns were then divided into two groups: patients reaching FiO2≤0.25 (OLVS Group, N.=28), and patients reaching FiO2>0.25 (No-OLVS Group, N.=23). RESULTS: Prior to surfactant administration OLVS Group, respect to No-OLVS Group, received a significantly higher continuous distending pressure (CDP): 12.8±1.1 cmH2O vs 11.2±1.3 cmH2O (P<0.0001) and a significantly lower FiO2: 0.25±0.01 vs 0.35±0.06 (P<0.0001). A multivariate modeling approach confirmed that OLVS was significantly associated to the need for less surfactant doses (OR 0.19[95% CI 0.05-0.84]), a decreased risk of ductus arteriosus surgically ligated (OR 0.13[95% CI 0.02-0.86]) and to a lower number of ventilation hours before extubation: -152 (95% CI -284- -20). CONCLUSION: OLVS to fully recruit the lungs achieving FiO2≤0.25 during elective HFOV is associated with better short-term pulmonary outcomes respect to a strategy where the patients received a FiO2>0.25 during the recruitment phase. Utilizing HFOV in this way provides a more effective means to recruit and protect acutely injured lungs.

State of the art of palliative therapy.

Bone pain in advanced stages of cancer significantly decreases the patient's quality of life having a great impact on physical, physiological and social functioning. About 65% of patients with prostate or breast cancer will experience symptomatic skeletal metastases. Bone pain sustained by osseous metastases represents the most frequent kind of pain and its clinical presentation and characteristics differ from other type of neoplastic pain (i.e., neuropathic or visceral ones). Pathophysiology of bone pain is not yet completely understood but a general mechanism including infiltration of bone tissue associated with osteolysis and release of biological active molecules able to stimulate peripheral nervous terminals, seems to be principally involved. In oncological practice, painful skeletal metastases are managed by different multidisciplinary modalities which include the use of systemic analgesics (i.e., bisphosphonates), antineoplastic agents (i.e., hormones and chemotherapeutics), external beam radiotherapy, interventional radiology and radiopharmaceuticals. In this review we will discuss the state of the art of palliative therapy of bone pain with particular emphasis to the current approved radiopharmaceuticals, focusing on indications, patient selection, efficacy and toxicity. Some remarks on new or under developing strategies in systemic metabolic radiopharmaceutical therapy will be reported.

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review.

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.

[Validation of an hourly transcutaneous bilirubin nomogram in a population of term or late preterm newborn infants: preliminary results]. / Validazione di un nomogramma orari di bilirubina transcutanea in una popolazione di neonati a termine o late preterm: risultati preliminari.

OBJECTIVE: The aim of this study was to asses the validity of the TCB nomogram for the European population for predicting significant hyperbilirubinemia in healthy term and late-preterm newborns. METHODS: This observational study was conducted from February 2009 to December 2009 in the well-baby nurseries of Gemelli hospital of Rome. The predictive ability of the skin bilirubin (TCB) nomogram was prospectively assessed in 926 neonates with gestational age ?35 weeks. TCB was measured with Bilichek and total serum bilirubin (TSB) was contemporary assayed by the standard spectrophotometric method. Every neonate was assess for a single TCB and TSB value. RESULTS: The mean TSB values was 8.2 +/- 3.2 mg/dl, while the mean TCB values was 9.5 +/- 3.6 mg/dl A sensitivity of 100% and a negative predictive value of 100% were obtained with a single bilirubin determination applying the 75 degrees percentile of our nomogram. CONCLUSION: The 75 degrees percentile of the skin bilirubin nomogram for the European population in the first 96 hours of life is able to predict all neonates at risk of severe hyperbilirubinemia. It could facilitate a safe discharge from the hospital and a targeted intervention and follow-up reducing the need for blood samples.

Lutein absorption in premature infants.

The objective of this study was to measure lutein and zeaxanthin plasma levels after oral lutein administration in preterm infants. Lutein was given orally in a single dose of 0.5 mg/kg to 10 preterm infants at a mean age of 52 h of life. Plasma lutein and zeaxanthin were measured before and 6, 24, 48, and 120 h after lutein administration. All infants had detectable plasma levels of lutein and zeaxanthin before treatment. Lutein concentration increased by 13.5% at 6 h and by 16.7% at 24 h, and returned to the basal level at 120 h after treatment. Zeaxanthin remained unchanged during the study period. Lutein is well absorbed in preterm infants when given orally. The clinical impact of increasing plasma lutein concentrations on macular development and visual function needs further investigation.

Attempt to improve transcutaneous bilirubinometry: a double-blind study of Medick BiliMed versus Respironics BiliCheck.

OBJECTIVES: To compare the accuracy of a new transcutaneous bilirubinometer, BiliMed (Medick SA, Paris, France) with BiliCheck (Respironics, Marietta, GA, USA), a widely available instrument, and with total serum bilirubin measurement. DESIGN: A prospective double-blind study comparing the two devices was carried out. 686 healthy newborns needing measurement of their bilirubin were enrolled over a 4-month period. Serum and transcutaneous bilirubin measurements were taken with both devices within 15 minutes. The order of use of the instruments was randomised. SETTING: Well-baby nursery ward in a university hospital, tertiary referral centre. RESULTS: The linear regression analysis showed a better correlation between BiliCheck and serum bilirubin (r = 0.75) than between BiliMed and serum bilirubin (r = 0.45). BiliCheck variability (+/-2 SD of the mean bias from serum bilirubin) was within -87.2 to 63.3 micromol/l, while BiliMed variability was within -97.5 to 121.4 micromol/l. The receiver operating characteristic analysis (for serum bilirubin levels >205.2 micromol/l or >239.4 micromol/l) showed significantly higher areas under the curve for BiliCheck than those for BiliMed (p<0.001). CONCLUSIONS: Despite the potential practical advantages of BiliMed, its reduced diagnostic accuracy in comparison with BiliCheck does not justify its use in clinical practice.

Antenatal post-hemorrhagic ventriculomegaly: a prospective follow-up study.

OBJECTIVE: The aim of this study was to evaluate the presence and the severity of neurological and cognitive impairment at 2 years of age in 16 infants (9 term born, 7 preterm of mean gestation 33.6 weeks) with cerebral ventriculomegaly of antenatal onset associated with intraventricular haemorrhage. METHODS: Ventricular dilatation, with or without associated lesions, was, with one exception, not identified on the antenatal routine scan at approximately 22 weeks but was obvious on the scans performed between weeks 27 and 33. In 8 of the 16 cases there were signs of parenchymal involvement or of abnormalities of the corpus callosum or cerebellum. In all patients the diagnosis of antenatal IVH was confirmed by early neonatal imaging. Outcome was measured using the Hammersmith infant neurological examination and the Griffiths developmental scales at 2 years. RESULTS AND CONCLUSIONS: At 2 years, 8 infants had normal motor outcome and 8 had cerebral palsy. The presence and severity of cerebral palsy or neurodevelopmental delay was not always related to the magnitude or symmetry of the ventricular dilatation per se. The presence of associated lesions was a negative prognostic marker. The early development of epilepsy was also associated with an abnormal outcome.

Is serum troponin T a useful marker of myocardial damage in newborn infants with perinatal asphyxia?

AIM: To assess the correlation of echocardiographic signs of myocardial damage to serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal asphyxia. METHODS: Electocardiograms (ECG) and echocardiograms (Echo) were obtained during the first 24 h of life from 29 asphyxiated and 30 control infants and correlated with cTnT concentrations. The echocardiographic parameters included systolic ventricular performance, preload, afterload, diastolic function, stroke volume (SV), left ventricular output (LVO), hyperechogenity of the papillary muscles and insufficiency of the atrioventricular valves. RESULTS: LVO and SV were lower but CTnT were significantly higher in asphyxiated than in control infants: 0.15 (010-0.23) vs. 0.05 (0.02-0.13), p < 0.001). Asphyxiated infants with signs of myocardial damage were associated with significantly higher cTnT than those without, 0.20 (0.11-0.28) and 0.11 (0.05-0.14 ug/L), p = 0.04. CONCLUSION: Cardiac troponin may prove to be valuable in evaluating myocardial damage in birth asphyxia. However, the degree of prematurity may complicate the assessment.

Outcome of newborns with asymptomatic monomorphic ventricular arrhythmia.

BACKGROUND: Frequent premature ventricular contractions (PVCs), couplets (CPLTs) and episodes of ventricular tachycardia are extremely rare in the neonatal population. Limited information is available with regard to clinical relevance and outcome. OBJECTIVES: To evaluate the clinical characteristics and outcomes of a group of newborns with ventricular arrhythmias without heart disease. PATIENTS AND DESIGN: Between January 2000 and January 2003, 16 newborns with ventricular arrhythmias in the absence of heart disease were studied. The newborns were divided into three groups: PVC group (n = 8), CPLT group (n = 4) and ventricular tachycardia group (n = 4). All patients underwent physical examination, electrocardiography, Holter monitoring and echocardiography at diagnosis and at follow-up (1, 3, 6 and 12 months, and yearly thereafter). RESULTS: Mean (standard deviation, SD) age of the patients was 3 (1.19) days in the PVC group, 3.25 (0.95) days in the CPLT group and 6.5 (9.1) days in the ventricular tachycardia group. Median follow-up was 36 months (range 24-48 months). PVCs disappeared during follow-up in all the neonates, in the PVC group, at a mean (SD) age of 2.1 (1.24) months; in the CPLT group, couplets disappeared at a mean (SD) age of 6.5 (1) months. All patients with ventricular tachycardia were treated; ventricular tachycardia disappeared at a mean (SD) age of 1.7 (0.9) months. Neither death nor complications occurred. CONCLUSIONS: Ventricular arrhythmias in newborns without heart disease have a good long-term prognosis. Frequent PVCs and CPLTs do not require treatment. Sustained ventricular tachycardia or high-rate ventricular tachycardia must be treated, but the prognosis is generally favourable.

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants.

OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.

Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants.

The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.

Adrenocortical function and chronic lung disease of pre-maturity: an unresolved problem?

The aim of this study was to investigate the relationship between adrenocortical function and chronic lung disease (CLD) of pre-term infants. Plasma F and ACTH were measured at 7, 14, 21 and 28 days of life in 25 pre-term infants with gestational age < or = 32 weeks and birth weight < or = 1,250 g. Fourteen infants developed CLD (CLD group) and 11 recovered without CLD (NOCLD group). Response to ACTH stimulation was tested on days 7 and 28. The results show that at the 7th day of life plasma F and ACTH levels were similar in the NOCLD and CLD group. CLD group had significantly higher plasma F and ACTH concentrations at the 14th (p=0.006 for F and p=0.020 for ACTH) and at the 21st (p=0.008 for F and p=0.024 for ACTH) day of life, while no significant differences were detected at the 28th day of life. The response to ACTH stimulation test was similar between the NOCLD and CLD group. These data demonstrate the lack of any significant association between adrenal insufficiency and CLD and discourage the use of baseline or stimulated plasma F levels to predict the development of CLD in pre-term infants.

A three year follow up of preterm infants after moderately early treatment with dexamethasone.

OBJECTIVE: To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants. METHODS: Thirty preterm infants enrolled in a randomised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up. Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life, and 15 babies were untreated. Five infants in each group received open label steroids to facilitate extubation later in their clinical course. Growth and neurodevelopmental outcome are reported. RESULTS: The mean body weight, height, and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies. There was no significant difference between treated and control groups with respect to incidence of cerebral palsy, major neurosensory impairment, mean intelligence quotient scores, and behavioural abnormalities. CONCLUSIONS: Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants. Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment. The full extent of the risk will only be known when more trials have reported follow up data.

Early changes of pulmonary mechanics to predict the severity of bronchopulmonary dysplasia in ventilated preterm infants.

OBJECTIVES: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity. METHODS: Pulmonary mechanics were studied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed using a previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcome was classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4). RESULTS: Of the 52 infants, 39 survived to 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patent ductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10 days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probability of developing severe BPD. Respiratory system resistance did not show any predictive value. CONCLUSIONS: Our findings indicate that low lung compliance values determined on the 7th and 10th days of life are a reliable predictive tool of the severity of later BPD.