Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

BACKGROUND AND AIMS: Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. METHODS AND RESULTS: The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). CONCLUSIONS: In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients.

Resistance to the atypical retinoid ST1926 in SK-N-AS cells selected the subline rAS-ST with enhanced sensitivity to ATRA mediated by not conventional mechanisms: DNA damage, G2 accumulation and late telomerase inhibition.

BACKGROUND AND PURPOSE: 13-cis-Retinoic acid represents a well-established clinical strategy for the management of minimal residual disease of high risk neuroblastoma (NB) patients. However, the clinical efficacy on the overall survival of these patients remains limited, addressing the issue of better understanding the molecular mechanisms and intracellular pathways mediating Retinoic Acid (RA) clinical effects. EXPERIMENTAL APPROACH: This work investigates the mechanism underlying the sensitivity/resistance to RA in NB by taking advantage of the paired SK-N-AS/rAS-ST cells showing different responsivity to ATRA. The subline rAS-ST was selected by inducing resistance to the novel retinoid ST1926 in the NB SK-N-AS cell line. KEY RESULTS: Resistance to ST1926 was neither dependent on cellular uptake nor on multi-drug resistance phenotype. Rather, both delayed/lower DNA damage and apoptosis appeared involved in reduced sensitivity of rAS-ST cells to ST1926. This subline showed enhanced responsivity to ATRA compared to the wt counterpart, that was associated with enhanced RARα/ß expression, DNA damage, G2 accumulation, PI3K/AKT pathway inhibition, cellular differentiation and delayed telomerase inhibition, without involvement of either p27/p53 or caspase-mediated apoptosis. CONCLUSIONS AND IMPLICATIONS: The present data add important information to the understanding of RA sensitivity in NB, providing further insights towards a more efficacious clinical use of this drug.

Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Effectiveness of a prematurity-based protocol for management of infants born to mothers with Group B Streptococcus colonisation.

The aim of this study was to validate the efficacy of a protocol for the management of infants born to colonised mothers with Group B Streptococcus (GBS). We studied a cohort of newborns admitted at the A. Gemelli University Hospital between May 2006 and December 2009. A total of 1,108 were newborns of mothers with GBS; 178 were children of mothers with unknown GBS status. Newborns were managed according to the care protocol in use at our division. Infected infants were born to mothers who underwent inadequate intrapartum antibiotic prophylaxis (IAP). No mother with complete IAP had an infected newborn. The incidence of invasive GBS infection in newborns of mothers with GBS was 0.4% and in newborns of mothers with unknown GBS status was 2.2%. Only 17.4% of newborns of mothers with GBS had risk factors. The complete IAP should always be performed regardless of the presence or the absence of risk factors. The care protocol applied offers successful management of the newborns of mothers with GBS, based on the correct execution of IAP, considering as a primary risk factor, the gestational age of < 35 weeks.

Spontaneous neonatal pneumomediastinum: radiological or clinical diagnosis?

Spontaneous neonatal pneumomediastinum (PNM) is associated with the aspiration of blood or meconium and birth-related trauma and it seems to be more frequent in post-term newborns. It is generally asymptomatic, but it is occasionally accompanied by mild tachypnoea. Only rarely, it requires oxygen therapy or develops into pneumothorax. To evaluate the relationship between the radiological and clinical diagnosis in this uncommon problem, from January 2005 to August 2009, 35 newborns with spontaneous PNM were enrolled in the study. Treatment protocol provides for execution of a chest X-ray, clinical check, SatO(2) and heart rate monitoring. Clinical diagnosis was accomplished particularly early, within the first 24 h of life. Paraphonic and distant tones discovered by cardio-auscultatory exam disappeared within the following 72 h. A total of 28 newborns were asymptomatic (80%); seven were symptomatic (20%); five had transient tachypnoea of the newborn; two developed an RDS, with Silverman score ≥ 3 and required O(2) therapy. It is necessary to affirm the importance of early diagnosis of this condition, carrying out careful monitoring of newborns at risk, to begin timely therapeutic treatments, as oxygen-therapy and to heighten alertness for complications, such as pneumothorax.

Platinum compounds and sodium metabolism in children with diencephalic glioma.

In this brief report we have described eight children affected by optic pathway/hypothalamus gliomas and treated with carboplatin and/or cisplatin, which developed a derangement of sodium and water metabolism, due to diabetes insipidus (DI) or to syndrome of inappropriate antidiuretic hormone secretion (SIADH) after surgical resection. In four out of these eight patients the treatment with platinum compounds produced prolonged haematological toxicity and in five out of them it caused neurosensorial bilateral hypoacusia. In addition cisplatin worsened electrolytes disturbances. Hence children with DI or SIADH should be carefully monitored before, during and after the treatment with platinum compounds.

Current practice and recent advances in pediatric pain management.

BACKGROUND: Differently from the adult patients, in pediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, selection of appropriate pain assessment tools should consider age, cognitive level and the presence of eventual disability, type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drugs pharmacokinetics should facilitate a better management of childhood pain. AIM: The objective of this review is to discuss current practice and recent advances in pediatric pain management. METHODS: Using PubMed we conducted an extensive literature review on pediatric pain assessment and commonly used analgesic agents from January 2000 to January 2012. CONCLUSIONS: A multimodal analgesic regimen provides better pain control and functional outcome in children. Cooperation and communication between the anaesthesiologist, surgeon, and paediatrician are essential for successful anaesthesia and pain management.

Comparison between two treatment protocols with recombinant human erythropoietin (rHuEpo) in the treatment of late anemia in neonates with Rh-isoimmunization.

OBJECTIVE: [corrected] The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. METHODS: A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. RESULTS: The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%), whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%). The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05). Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05). CONCLUSIONS: Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects.

Human parvovirus B 19 and Epstein-Barr virus co-infection in a child with hereditary spherocytosis.

BACKGROUND: In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequently involved in pure red-cell aplastic crises. Furthermore, it may inhibit three-lineage haematopoiesis in the bone marrow, causing severe pancytopenia. In such patients, Epstein Barr virus (EBV) infection also seems to share the same mechanism as HPV B19 in inducing bone marrow aplasia, but at present the clinical effect of an infection sustained by both viruses is unknown. CLINICAL REPORT: We present a 7-year-old boy affected by hereditary spherocytosis (HS) who suffered from transient aplastic crisis, in whom laboratory findings revealed a double HPV B19 and EBV infection. CONCLUSIONS: To our knowledge, this is the first report of a case of HPV B19 and EBV co-infection diagnosis in a paediatric patient. Despite underlying HS, no signs of haemolytic anaemia were detected, but the infection only produced transient pancytopenia. Nevertheless, the reason why there was no additive effect of the two viruses on the aplastic crisis is still unclear.

Massive venous thrombosis of inferior vena cava as primary manifestation of renal Ewing's sarcoma.

We report an extraordinarily rare case of a 17-year-old male with an extraskeletal Ewing's sarcoma (ESS) of the kidney and a massive thrombosis involving the inferior vena cava (IVC), from the iliac axis to the right atrium. This onset resembled renal cell carcinoma (RCC), although histological examination revealed it was an extraskeletal Ewing's sarcoma/peripheral neuro-ectodermal tumor (EES/PNET). EES/PNET should benefit from neoadjuvant chemotherapy to reduce the risk of metastasis and of recurrent disease due to delay in suitable treatment. Therefore, in the presence of a renal mass with tumor extension of IVC, it is reasonable to bear in mind that other tumors, apart from RCC, could occur. In such cases, a US or CT-scan guided biopsy could be useful.

Pretreatment neuropsychological deficits in children with brain tumors.

Treatment of childhood brain cancer has been associated with long-term cognitive morbidity in children. In the present study, the cognitive status of children with brain tumors was examined prior to any treatment to single out the role of tumor and tumor-related factors in cognitive deficits. Eighty-three children with newly diagnosed brain tumors (mean age, 8.6 years; range, 7 months to 16.6 years; median, 9.4 years) completed an extensive battery of age-related tests to assess cognitive function before any therapeutic intervention. Magnetic resonance imaging (MRI) was used to determine tumor site and volume and tumor-related factors. Performance under test was compared with symptom duration, neurological status, epilepsy, and MRI. Cognitive difficulties are detected at diagnosis in as many as 50% of patients for some cognitive domains; 6% of patients present with true-diagnosed mental retardation. The location of the tumor is the principal determinant of cognitive deficits, with major impairment in children with cortical tumors. Symptom duration and the presence of epilepsy are significantly associated with neuropsychological disabilities, while neuroradiological tumor-related variables do not correlate clearly with neurocognitive performance. The knowledge of the pre-existing cognitive deficits is critical to evaluate the results of treatment, providing a baseline for assessing the true impact of therapy in determining cognitive decline. In addition, the study suggests that some clinical variables require careful monitoring, because they could be specifically implicated in the neuropsychological outcome; the efforts to reduce the impact of these factors could ameliorate long-term prognosis.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

Errors involving patients receiving intrathecal chemotherapy.

Errors involving patients receiving intrathecal chemotherapy are a significant problem in oncology. Despite the improvement in the management of antineoplastic agents, unintentional intrathecal administration of chemotherapic drugs that are indicated only for systemic administration or intrathecal overdose of drugs regularly used for intrathecal chemotherapy, continue to occur. These events can result in severe neurotoxicity, usually fatal in outcome. We review reported cases of medication errors in intrathecal administration of chemotherapy described in the literature. Diverse rescue therapies have been proposed but the most effective means of managing these errors remains prevention.

Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblastic leukaemia: safety, efficacy and their correlation with pain neuromediator expression.

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.

Central pontine and extrapontine myelinolysis in a pediatric patient following rapid correction of hypernatremia.

Central pontine and extrapontine myelinolysis are uncommon disorders characterized by distinctive clinical features and typical findings on neuroimaging. Only a few cases are reported in the pediatric age group. We describe the case of a leukemic, malnourished 14-year-old boy with a high serum sodium concentration that gradually increased to 170 mmol/L. During a septic shock episode, hydration with a low sodium concentration at the rate of 104 mL/h for 24 h was administered. A rapid correction of the high serum sodium occurred, exceeding 0.5 mmol/L/h. The following day the patient developed rapid and progressive neurological impairment with clinical features characteristic of central pontine and extrapontine myelinolysis. Magnetic resonance imaging confirmed the diagnosis 11 days later. The patient was treated with steroids and intravenous immunoglobulins. He achieved an almost full neurological recovery and radiological improvement. The reported case demonstrates that central pontine and extrapontine myelinolysis can occur after excessively rapid correction of hypernatremia.

Severe hyperleukocytosis and multifocal intracranial haemorrhage: not always a fatal outcome.

Severe hyperleukocytosis caused by acute lymphoblastic leukaemia (ALL) is associated with an increased risk of early death due to the intracranial haemorrhage. We report on a boy who presented with ALL with an extremely high leukocyte count, who developed neurological deterioration due to multiple intracerebral haemorrhages. Adequate measures for managing this medical emergency include appropriate supportive measures and initiation of therapy to prevent symptoms of leukostasis. Aggressive measures as a decompressive craniectomy should be considered to improve the poor outcome observed in this subset of patients.

NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children.

BACKGROUND: Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of specific biomarkers, such as cytokines, neurotrophic factors, and neuron-specific enolase (NSE). NSE is associated with neuronal damage, while neurotrophic factors play a neuroprotective role due to their ability to modulate neuronal precursor biosynthesis, such as doublecortin (DCX). However, the relationships between the expression of these factors and the severity and outcome of TBI are not understood. METHODS: To determine whether the concentrations of neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]), DCX, and NSE in the CSF of children with TBI correlate with the severity of brain damage and neurologic outcome, we prospectively collected CSF samples from 32 children at 2 and 48 hours after admission for severe TBI and from 32 matched controls. Severity of TBI was evaluated by Glasgow Coma Scale and neurologic outcome by Glasgow Outcome Score. RESULTS: Early NGF, DCX, and NSE concentrations correlated significantly with the severity of head injury, whereas no correlation was found for BDNF and GDNF. Furthermore, NGF and DCX upregulation and lower NSE expression were associated with better neurologic outcomes. No significant association was found between BDNF and GDNF expression and outcome. CONCLUSIONS: Nerve growth factor (NGF), doublecortin (DCX), and neuron-specific enolase concentrations in the CSF are useful markers of brain damage following severe traumatic brain injury (TBI). NGF and DCX upregulation correlates also with better neurologic outcome and could be useful to obtain clinical and prognostic information in children with severe TBI.

Primary Sjögren's syndrome mimicking lymphoma in a pediatric patient. A rare and possibly misdiagnosed condition.

A 12-year-old girl presented at the Oncoemato-logic Department with an acute onset of generalized lymphadenopathy. Lymphoproliferative disorders were highly suspected. Biopsied cervical and inguinal lymph node disclosed neither malignant cells nor monoclonal proliferation of lymphocytes. Revaluating the diagnosis, anamnestic data revealed multiple episodes of bilateral parotid swelling since age one, without systemic symptoms. Laboratory investigations, parotid ecography, Schirmer test revealed Sjogren's syndrome without associated disease. Sjogren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition.