Elio Castagnola - Academia.edu (original) (raw)

Papers by Elio Castagnola

Research paper thumbnail of Bacteremias in children receiving hemopoietic SCT

Bone Marrow Transplantation, 2008

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Research paper thumbnail of Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

Acta Paediatrica, 2007

The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognit... more The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.

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Research paper thumbnail of A validated LC–MS/MS method for the quantification of piperacillin/tazobactam on dried blood spot

Bioanalysis, 2014

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Research paper thumbnail of Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation

The Lancet Oncology, 2014

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Research paper thumbnail of Candida Speciation, Antifungal Treatment and Adverse Events in Pediatric Invasive Candidiasis

The Pediatric Infectious Disease Journal, 2014

A multi-national prospective study of pediatric patients with invasive candidiasis between August... more A multi-national prospective study of pediatric patients with invasive candidiasis between August 2007 and September 2012 was performed and included 441 infections. Variation in infecting Candida species and antifungals used was noted between US and non-US sites. Antifungal-associated adverse events were most common with polyene use.

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Research paper thumbnail of Comment to Letter to the Editor regarding the article by R. Casciaro et al. titled ‘Role of nebulized amphotericin B in the management of allergic bronchopulmonary aspergillosis in cystic fibrosis: case report and review of literature’

Journal of Chemotherapy, 2014

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Research paper thumbnail of Micafungin for the treatment of proven and suspected invasive candidiasis in children and adults: findings from a multicenter prospective observational study

BMC Infectious Diseases, 2014

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Research paper thumbnail of Infectious Complications of Antineoplastic Chemotherapy in Children with Acute Leukemia or Solid Tumors

Pediatric Cancer, 2013

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Research paper thumbnail of Tuberculosis diagnosed after chemotherapy for presumed mediastinal malignant neoplasia

Pediatric Blood & Cancer, 2014

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Research paper thumbnail of Conditions associated with infections of indwelling central venous catheters in cancer patients: a summary

British Journal of Haematology, 2003

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Research paper thumbnail of Infections after stem cell transplantation in children: state of the art and recommendations

Bone Marrow Transplantation, 2001

At the workshop on infections after stem cell transplantation (SCT) in children, the following to... more At the workshop on infections after stem cell transplantation (SCT) in children, the following topics were introduced by invited speakers and discussed with the audience: empirical antimicrobial therapy in the pre-engraftment period, early diagnosis of fungal and viral infections and possibilities to treat them and the possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment period mostly are unexplained, and in about one quarter due to bacteremia, mostly by Gram-positive cocci. No single drug or combination of drugs used for antimicrobial therapy is superior, neither does it cover 100% of the pathogens. Close microbiological surveillance of the patients and knowledge of the local microbial epidemiology are requested for optimal therapy. Early fungal infections are reactivations of pre-SCT infections, late fungal infections mostly are associated with failure of engraftment or GvHD and its treatment. Except for suggestive ultrasound or CT-scan abnormalities, the possibilities for early diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to prevent Candida albicans invasion. A number of new antifungal drugs are being tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after SCT, causing severe disease with a high mortality, especially in non-HLA-identical donor-recipient combinations. Frequent surveillance cultures for CMV and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV, EBV and adenoviruses all have their own contribution to the early diagnosis of dissemination of the viral infection. Therapeutical possibilities, except with respect to ganciclovir and foscarnet for CMV infection, are still limited. The effectiveness of cidofovir is under study. Adoptive therapy with virus-specific CTL's probably represents the new frontier. G-CSF administration early after SCT has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics and total parenteral nutrition requirement in children undergoing allogeneic and autologous BMT. No benefit is observed in children undergoing peripheral blood SCT. The routine use of G-CSF in the latter group of patients is not justified.

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Research paper thumbnail of Immunization after the elective end of antineoplastic chemotherapy in children

Pediatric Blood & Cancer, 2009

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Research paper thumbnail of Quinolone prophylaxis for bacterial infections in afebrile high risk neutropenic patients

European Journal of Cancer Supplements, 2007

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Research paper thumbnail of Emerging fungal pathogens, drug resistance and the role of lipid formulations of amphotericin b in the treatment of fungal infections in cancer patients: A review

International Journal of Infectious Diseases, 1999

The incidence of life-threatening invasive fungal infections in immunocompromised patients has in... more The incidence of life-threatening invasive fungal infections in immunocompromised patients has increased dramatically in recent years. Candida spp other than C. albicans are increasingly being isolated, and Aspergillus infections also are on the increase, as well as infections due to previously uncommon organisms. It is likely that this phenomenon is multifactorial in origin, although the extensive use of antifungal prophylaxis may have played a role, especially for the emergence of non-albicans Candida. Amphotericin B remains the antifungal agent with the broadest spectrum of action available and is thus the standard treatment for immunocompromised patients with proven or suspected fungal infections, especially aspergillosis. However, its potential for nephrotoxicity limits its usefulness. Lipid formulations of amphotericin B may allow therapy to be administered with reduced renal toxicity. Three different lipid formulations of amphotericin B currently are available. These compounds have different pharmacokinetic properties and seem to achieve higher serum or tissue concentrations than amphotericin B. This statement is based on animal models and scattered human data. At present, there are no studies comparing the lipid formulations with each other and only a few randomized trials comparing them with conventional amphotericin B. However, a number of open clinical trials and compassionate-use protocols suggest that lipid-based forms of amphotericin B can achieve good response rates with minimal toxicity in patients with a variety of invasive mycoses, including those who have proved refractory or intolerant to previous therapy with conventional amphotericin B. Unfortunately, the cost of these compounds remains high and may represent a limiting factor to their use.

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Research paper thumbnail of Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours

European Journal of Cancer, 2001

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Research paper thumbnail of Vertical transmission of hepatitis C virus infection: Usefulness of viremia detection in HIV-seronegative hepatitis C virus–seropositive mothers

Journal of Pediatrics, 1998

Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertica... more Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertical transmission of hepatitis C virus from human immunodeficiency virus–negative mothers. Forty-five mothers were hepatitis C virus–RNA positive: 4 of 45 children were positive at birth and during follow-up. The level of viremia plays an important role in vertical transmission. (J Pediatr 1998;132:167-9)

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Research paper thumbnail of Association between Antifungal Prophylaxis and Rate of Documented Bacteremia in Febrile Neutropenic Cancer Patients

Clinical Infectious Diseases, 2001

Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febr... more Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febrile neutropenia. This correlation was investigated among 3002 febrile neutropenic patients enrolled in 4 trials during 1986-1994. Globally, 1322 patients (44%) did not receive antifungal prophylaxis; 835 (28%) received poorly absorbable antifungal agents and 845 (28%) received absorbable antifungal agents. The rates of bacteremia for these groups were 20%, 26%, and 27%, respectively (P=.0001). In a multivariate model without including antifungal prophylaxis, factors associated with bacteremia were: age, duration of hospitalization, duration of neutropenia before enrollment, underlying disease, presence of an intravenous catheter, shock, antibacterial prophylaxis, temperature, and granulocyte count at onset of fever. When antifungal prophylaxis was included, the adjustment quality of the model improved slightly (P=.05), with an odds ratio of 1.19 (95% confidence interval [CI], 0.92-1.55) for patients receiving nonabsorbable and 1.42 (95% CI, 1.07-1.88) for those who were receiving absorbable antifungal agents. Antifungal prophylaxis with absorbable agents might have an impact on the rate of documented bacteremia in febrile neutropenia. This effect should be confirmed prospectively.

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Research paper thumbnail of Retinol (vitamin A) and retinol-binding protein serum levels in children with cancer at onset

Nutrition, 1997

The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagn... more The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagnosed neoplasia (NDN) admitted to the Department of Hematology-Oncology of G. Gaslini Institute. Vit A levels, retinol-binding protein (RBP), and nutritional status were evaluated in 54 ...

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Research paper thumbnail of Role of G-CSF GM-CSF in the management of infections in preterm newborns: an update

Early Human Development, 2014

Neutropenia (definable as an absolute granulocyte count &... more Neutropenia (definable as an absolute granulocyte count <1,000/μL in neonates) is a relatively frequent condition in small for gestational age and/or low birth weight neonates. Colony stimulating factors (CSF), namely granulocyte- (G-CSF) and granulocyte-macrophage- (GM-CSF) CSF, have been proposed for prophylaxis and therapy of severe infections in this condition. Available data do not support the use of these substances for prophylaxis of infections in the presence of neutropenia. On the contrary, there might be space for their use, mainly for G-CSF, in case of severe infectious complications in severely neutropenic neonates (absolute polymorphonuclear neutrophil count <500/μL) and/or in the presence of specific hematological diseases causing neutropenia.

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Research paper thumbnail of PNEUMOTHORAX AND PNEUMOCYSTIS PNEUMONIA IN AN INFANT WITH ACQUIRED IMMUNODEFICIENCY SYNDROME

The Pediatric Infectious Disease Journal, 1992

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Research paper thumbnail of Bacteremias in children receiving hemopoietic SCT

Bone Marrow Transplantation, 2008

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

Acta Paediatrica, 2007

The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognit... more The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.

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Research paper thumbnail of A validated LC–MS/MS method for the quantification of piperacillin/tazobactam on dried blood spot

Bioanalysis, 2014

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Research paper thumbnail of Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation

The Lancet Oncology, 2014

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Research paper thumbnail of Candida Speciation, Antifungal Treatment and Adverse Events in Pediatric Invasive Candidiasis

The Pediatric Infectious Disease Journal, 2014

A multi-national prospective study of pediatric patients with invasive candidiasis between August... more A multi-national prospective study of pediatric patients with invasive candidiasis between August 2007 and September 2012 was performed and included 441 infections. Variation in infecting Candida species and antifungals used was noted between US and non-US sites. Antifungal-associated adverse events were most common with polyene use.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Comment to Letter to the Editor regarding the article by R. Casciaro et al. titled ‘Role of nebulized amphotericin B in the management of allergic bronchopulmonary aspergillosis in cystic fibrosis: case report and review of literature’

Journal of Chemotherapy, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Micafungin for the treatment of proven and suspected invasive candidiasis in children and adults: findings from a multicenter prospective observational study

BMC Infectious Diseases, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Infectious Complications of Antineoplastic Chemotherapy in Children with Acute Leukemia or Solid Tumors

Pediatric Cancer, 2013

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Tuberculosis diagnosed after chemotherapy for presumed mediastinal malignant neoplasia

Pediatric Blood & Cancer, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Conditions associated with infections of indwelling central venous catheters in cancer patients: a summary

British Journal of Haematology, 2003

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Research paper thumbnail of Infections after stem cell transplantation in children: state of the art and recommendations

Bone Marrow Transplantation, 2001

At the workshop on infections after stem cell transplantation (SCT) in children, the following to... more At the workshop on infections after stem cell transplantation (SCT) in children, the following topics were introduced by invited speakers and discussed with the audience: empirical antimicrobial therapy in the pre-engraftment period, early diagnosis of fungal and viral infections and possibilities to treat them and the possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment period mostly are unexplained, and in about one quarter due to bacteremia, mostly by Gram-positive cocci. No single drug or combination of drugs used for antimicrobial therapy is superior, neither does it cover 100% of the pathogens. Close microbiological surveillance of the patients and knowledge of the local microbial epidemiology are requested for optimal therapy. Early fungal infections are reactivations of pre-SCT infections, late fungal infections mostly are associated with failure of engraftment or GvHD and its treatment. Except for suggestive ultrasound or CT-scan abnormalities, the possibilities for early diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to prevent Candida albicans invasion. A number of new antifungal drugs are being tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after SCT, causing severe disease with a high mortality, especially in non-HLA-identical donor-recipient combinations. Frequent surveillance cultures for CMV and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV, EBV and adenoviruses all have their own contribution to the early diagnosis of dissemination of the viral infection. Therapeutical possibilities, except with respect to ganciclovir and foscarnet for CMV infection, are still limited. The effectiveness of cidofovir is under study. Adoptive therapy with virus-specific CTL's probably represents the new frontier. G-CSF administration early after SCT has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics and total parenteral nutrition requirement in children undergoing allogeneic and autologous BMT. No benefit is observed in children undergoing peripheral blood SCT. The routine use of G-CSF in the latter group of patients is not justified.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Immunization after the elective end of antineoplastic chemotherapy in children

Pediatric Blood & Cancer, 2009

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Quinolone prophylaxis for bacterial infections in afebrile high risk neutropenic patients

European Journal of Cancer Supplements, 2007

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Emerging fungal pathogens, drug resistance and the role of lipid formulations of amphotericin b in the treatment of fungal infections in cancer patients: A review

International Journal of Infectious Diseases, 1999

The incidence of life-threatening invasive fungal infections in immunocompromised patients has in... more The incidence of life-threatening invasive fungal infections in immunocompromised patients has increased dramatically in recent years. Candida spp other than C. albicans are increasingly being isolated, and Aspergillus infections also are on the increase, as well as infections due to previously uncommon organisms. It is likely that this phenomenon is multifactorial in origin, although the extensive use of antifungal prophylaxis may have played a role, especially for the emergence of non-albicans Candida. Amphotericin B remains the antifungal agent with the broadest spectrum of action available and is thus the standard treatment for immunocompromised patients with proven or suspected fungal infections, especially aspergillosis. However, its potential for nephrotoxicity limits its usefulness. Lipid formulations of amphotericin B may allow therapy to be administered with reduced renal toxicity. Three different lipid formulations of amphotericin B currently are available. These compounds have different pharmacokinetic properties and seem to achieve higher serum or tissue concentrations than amphotericin B. This statement is based on animal models and scattered human data. At present, there are no studies comparing the lipid formulations with each other and only a few randomized trials comparing them with conventional amphotericin B. However, a number of open clinical trials and compassionate-use protocols suggest that lipid-based forms of amphotericin B can achieve good response rates with minimal toxicity in patients with a variety of invasive mycoses, including those who have proved refractory or intolerant to previous therapy with conventional amphotericin B. Unfortunately, the cost of these compounds remains high and may represent a limiting factor to their use.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours

European Journal of Cancer, 2001

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Vertical transmission of hepatitis C virus infection: Usefulness of viremia detection in HIV-seronegative hepatitis C virus–seropositive mothers

Journal of Pediatrics, 1998

Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertica... more Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertical transmission of hepatitis C virus from human immunodeficiency virus–negative mothers. Forty-five mothers were hepatitis C virus–RNA positive: 4 of 45 children were positive at birth and during follow-up. The level of viremia plays an important role in vertical transmission. (J Pediatr 1998;132:167-9)

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Research paper thumbnail of Association between Antifungal Prophylaxis and Rate of Documented Bacteremia in Febrile Neutropenic Cancer Patients

Clinical Infectious Diseases, 2001

Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febr... more Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febrile neutropenia. This correlation was investigated among 3002 febrile neutropenic patients enrolled in 4 trials during 1986-1994. Globally, 1322 patients (44%) did not receive antifungal prophylaxis; 835 (28%) received poorly absorbable antifungal agents and 845 (28%) received absorbable antifungal agents. The rates of bacteremia for these groups were 20%, 26%, and 27%, respectively (P=.0001). In a multivariate model without including antifungal prophylaxis, factors associated with bacteremia were: age, duration of hospitalization, duration of neutropenia before enrollment, underlying disease, presence of an intravenous catheter, shock, antibacterial prophylaxis, temperature, and granulocyte count at onset of fever. When antifungal prophylaxis was included, the adjustment quality of the model improved slightly (P=.05), with an odds ratio of 1.19 (95% confidence interval [CI], 0.92-1.55) for patients receiving nonabsorbable and 1.42 (95% CI, 1.07-1.88) for those who were receiving absorbable antifungal agents. Antifungal prophylaxis with absorbable agents might have an impact on the rate of documented bacteremia in febrile neutropenia. This effect should be confirmed prospectively.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Retinol (vitamin A) and retinol-binding protein serum levels in children with cancer at onset

Nutrition, 1997

The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagn... more The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagnosed neoplasia (NDN) admitted to the Department of Hematology-Oncology of G. Gaslini Institute. Vit A levels, retinol-binding protein (RBP), and nutritional status were evaluated in 54 ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Role of G-CSF GM-CSF in the management of infections in preterm newborns: an update

Early Human Development, 2014

Neutropenia (definable as an absolute granulocyte count &... more Neutropenia (definable as an absolute granulocyte count <1,000/μL in neonates) is a relatively frequent condition in small for gestational age and/or low birth weight neonates. Colony stimulating factors (CSF), namely granulocyte- (G-CSF) and granulocyte-macrophage- (GM-CSF) CSF, have been proposed for prophylaxis and therapy of severe infections in this condition. Available data do not support the use of these substances for prophylaxis of infections in the presence of neutropenia. On the contrary, there might be space for their use, mainly for G-CSF, in case of severe infectious complications in severely neutropenic neonates (absolute polymorphonuclear neutrophil count <500/μL) and/or in the presence of specific hematological diseases causing neutropenia.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of PNEUMOTHORAX AND PNEUMOCYSTIS PNEUMONIA IN AN INFANT WITH ACQUIRED IMMUNODEFICIENCY SYNDROME

The Pediatric Infectious Disease Journal, 1992

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