Current practices for nutritional evaluation and care during the treatment of pediatric oncology patients: a survey among AIEOP centers.

Nutritional status plays a crucial role in the mortality rates of the pediatric oncology patients. However, there is a lack of systematic approaches for nutritional assessment in this population. This study aims to assess the current practice for nutritional assessment and care of pediatric cancer patients in Italy. A 25-items web-based, nation-wide questionnaire was circulated as of January 9, 2023 among physicians within the AIEOP network, composed of 49 national centers, out of which 21 routinely perform HCT. This survey examined the practices of 21 Italian pediatric oncology centers, revealing significant heterogeneity in nutritional practices. Only half of the centers routinely assessed all patients, utilizing different clinical and biochemical parameters. The use of neutropenic diets remained prevalent after chemotherapy or stem cell transplantation. CONCLUSION: This study underscores the pressing need for unified recommendations to improve nutritional care and potentially enhance outcomes for pediatric cancer patients. WHAT IS KNOWN: • The assessment and support of nutrition are gaining interest in the overall care of children with cancer. • The assessment and management of nutritional needs in pediatric cancer patients, including those undergoing hematopoietic cell transplantation, currently lack a systematic approach. WHAT IS NEW: • There is considerable variability in the nutritional assessment and support among Italian centers treating pediatric patients with cancer. • To enhance nutritional assessment and support for pediatric cancer patients, it is essential to establish shared national and international guidelines.

The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO).

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.

Myeloid Sarcoma: Diagnostic and Treatment Tools from a Monocentric Retrospective Experience.

Myeloid sarcoma (MS) is a very rare disease in both adults and children. Prognosis is poor in adults; in the pediatric age, the prognostic impact of extramedullary disease is controversial. Systemic therapy represents the mainstay of treatment even in isolated MS, but a comparison between different induction regimens is very limited in the literature. To date, it is still not clear if induction treatment should differ from that of other acute myeloid leukemias and stem cell transplant is considered for consolidation in both leukemic patients and in those with isolated disease. Our study describes a retrospective series of 13 cases of MS (adults and children), diagnosed and treated at our institute over 18 years. We report the results of immunophenotypic, cytogenetic and molecular studies, therapeutic approaches, and outcome, in order to establish the best strategy for patients' workup.

COVID-19 in Patients with Hematologic Disorders Undergoing Therapy: Perspective of a Large Referral Hematology Center in Rome.

INTRODUCTION: Patients with cancer may be more susceptible to and have higher morbidity and mortality rates from COVID-19 than the general population, while epidemiologic data specifically addressed to hematologic patients are limited. To investigate whether patients with hematologic diseases undergoing therapy are at increased risk for acquiring SARS CoV-2 infection compared to the general population, a retrospective study was carried out at a referral hematologic center in Rome, Italy, during the period of the greatest epidemic spread (March 8 to May 14, 2020). METHODS: All adult and pediatric patients with a diagnosis of a neoplastic or a nonneoplastic hematologic disease who underwent treatment (chemotherapy or immunosuppressive or supportive therapy) during the study period or in the previous 6 months were considered. The prevalence of COVID-19 in the overall outpatient and inpatient population undergoing hematologic treatment compared to that of the general population was analyzed. The measures taken to manage patients during the epidemic period are described. RESULTS: Overall, 2,513 patients with hematological diseases were considered. Out of 243 (9.7%) patients who were screened for SARS CoV-2, three of 119 (2.5%) outpatients with fever or respiratory symptoms and none of 124 asymptomatic patients were diagnosed with COVID-19. Three further patients were diagnosed with COVID-19 and managed in other hospitals in Rome. As of May 14, 2020, the prevalence of COVID-19 in our hematologic population accounted for 0.24% (95% CI 0.23-0.25; 6 of 2,513 patients: 1 case in every 419 patients) as compared to 0.12% (7,280 of 5,879,082 residents; 1 case in every 807 residents) in the general population (p = 0.14). Three of 6 patients diagnosed with COVID-19 required critical care and 2 died while still positive for SARS CoV-2. Out of 225 healthcare providers on duty at our Institution during the study period, 2 (0.9%) symptomatic cases were diagnosed with COVID-19. CONCLUSION: In our experience, the prevalence of COVID-19 in hematologic patients, mainly affected by malignancies, was not significantly higher compared to that of the general population. Definition of adapted strategies for healthcare services, while continuing to administer the standard hematologic treatments, represents the crucial challenge for the management of hematologic diseases in the COVID-19 era.

Gastroesophageal reflux disease vs. Panayiotopoulos syndrome: an underestimated misdiagnosis in pediatric age?

Autonomic signs and symptoms could be of epileptic or nonepileptic origin, and the differential diagnosis depends on a number of factors which include the nature of the autonomic manifestations themselves, the occurrence of other nonictal autonomic signs/symptoms, and the age of the patient. Here, we describe twelve children (aged from ten months to six years at the onset of the symptoms) with Panayiotopoulos syndrome misdiagnosed as gastroesophageal reflux disease. Gastroesophageal reflux disease and Panayiotopoulos syndrome may represent an underestimated diagnostic challenge. When the signs/symptoms occur mainly during sleep, a sleep EEG or, if available, a polysomnographic evaluation may be the most useful investigation to make a differential diagnosis between autonomic epileptic and nonepileptic disorders. An early detection can reduce both the high morbidity related to mismanagement and the high costs to the national health service related to the incorrect diagnostic and therapeutic approaches. To decide if antiseizure therapy is required, one should take into account both the frequency and severity of epileptic seizures and the tendency to have potentially lethal autonomic cardiorespiratory involvement. In conclusion, we would emphasize the need to make a differential diagnosis between gastroesophageal reflux disease and Panayiotopoulos syndrome in patients with "an unusual" late-onset picture of GERD and acid therapy-resistant gastroesophageal reflux, especially if associated with other autonomic symptoms and signs.

Pediatric Autologous Hematopoietic Stem Cell Transplantation: Safety, Efficacy, and Patient Outcomes. Literature Review.

Autologous stem cell transplantation (auto-HSCT) is a part of the therapeutic strategy for various oncohematological diseases. The auto-HSCT procedure enables hematological recovery after high-dose chemotherapy, otherwise not tolerable, by the infusion of autologous hematopoietic stem cells. Unlike allogeneic transplant (allo-HSCT), auto-HSCT has the advantage of lacking acute-graft-versus-host disease (GVHD) and prolonged immunosuppression, however, these advantages are counterbalanced by the absence of graft-versus-leukemia. Moreover, in hematological malignancies, the autologous hematopoietic stem cell source may be contaminated by neoplastic cells, leading to disease reappearance. In recent years, allogeneic transplant-related mortality (TRM) has progressively decreased, almost approaching auto-TRM, and many alternative donor sources are available for the majority of patients eligible for transplant procedures. In adults, the role of auto-HSCT compared to conventional chemotherapy (CT) in hematological malignancies has been well defined in many extended randomized trials; however, such trials are lacking in pediatric cohorts. Therefore, the role of auto-HSCT in pediatric oncohematology is limited, in both first- and second-line therapies and still remains to be defined. Nowadays, the accurate stratification in risk groups, according to the biological characteristics of the tumors and therapy response, and the introduction of new biological therapies, have to be taken into account in order to assign auto-HSCT a precise role in the therapeutic strategies, also considering that in the developmental age, auto-HSCT has a clear advantage over allo-HSCT, in terms of late sequelae, such as organ damage and second neoplasms. The purpose of this review is to report the results obtained with auto-HSCT in the different pediatric oncohematological diseases, focusing on the most significant literature data in the context of the various diseases and discussing this data in the light of the current therapeutic landscape.

Does NICE influence the adoption and uptake of generics in the UK?

The aim of this paper is to examine generic competition in the UK, with a special focus on the role of Health Technology Assessment (HTA) on generic market entry and diffusion. In the UK, where no direct price regulation on pharmaceuticals exists, HTA has a leading role for recommending the use of medicines providing a non-regulatory aspect that may influence the dynamics in the generic market. The paper focuses on the role of Technology Appraisals issued by the National Institute for Health and Care Excellence (NICE). We follow a two-step approach. First, we examine the probability of generic entry. Second, conditional on generic entry, we examine the determinants of generic market share. We use data from IQVIA British Pharmaceutical Index (BPI) for the primary care market for 60 products that lost patent between 2003 and 2012. Our results suggest that market size remains one of the main drivers of generic entry. After controlling for market size, intermolecular substitution and difficulty of manufacturing increase the likelihood of generic entry. After generic entry, our estimates suggest that generic market share is highly state dependent. Our findings also suggest that while NICE recommendations do influence generic uptake, there is only marginal evidence they affect generic entry.

A review of current induction strategies and emerging prognostic factors in the management of children and adolescents with acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia is the most frequent hematologic malignancy in children. Almost 95% of children potentially achieve a complete remission after the induction treatment, but over the last years, new insights in the genomic disease profile and in minimal residual disease detection techniques have led to an improvement in the prognostic stratification, identifying selected patients' subgroups with peculiar therapeutic needs. AREAS COVERED: According to a comprehensive search of peer-review literature performed in Pubmed, in this review we summarize the recent evidences on the induction treatment strategies comprised in the children acute lymphoblastic leukemia scenario, focusing on the role of key drugs such as corticosteroids and asparaginase and discussing the crucial significance of the genomic characterization at baseline which may drive the proper induction treatment choice. EXPERT OPINION: Current induction strategies already produce durable remissions in a significant proportion of standard-risk children with acute lymphoblastic leukemia. A broader knowledge of the biologic features related to acute lymphoblastic leukemia subtypes with worse prognosis, and an optimization of targeted drugs now available, might lead to the achievement of long-term molecular remissions in this setting.

Vitamin K deficiency: a case report and review of current guidelines.

BACKGROUND: Vitamin K, a fat soluble vitamin, is a necessary cofactor for the activation of coagulation factors II, VII, IX, X, and protein C and S. In neonatal period, vitamin K deficiency may lead to Vitamin K Deficiency Bleeding (VKDB). CASE PRESENTATION: We present the case of a 2 months and 20 days Caucasian male, presented for bleeding from the injections sites of vaccines. At birth oral vitamin K prophylaxis was administered. Neonatal period was normal. He was exclusively breastfed and received a daily oral supplementation with 25 µg of vitamin K. A late onset vitamin K deficiency bleeding was suspected. Intravenous Vitamin K was administered with complete recovery. CONCLUSIONS: Nevertheless the oral prophylaxis, our case developed a VKDB: it is necessary to revise the current guidelines in order to standardize timing and dosage in different clinical conditions.

Fatal varicella pneumonia in an unvaccinated child with Down Syndrome: a case report.

BACKGROUND: Varicella is an acute infectious disease common during childhood. It has mostly an uncomplicated course in early childhood. Neverthless, it may result in severe complications, especially in particular age groups and clinical conditions. Down Syndrome represents a risk factor for developing complications, because of the frequent comorbidities and their immunodeficiency. CASE PRESENTATION: A 2-year-old white Caucasian female affected by Down Syndrome was referred to our hospital for cardiac arrest in course of varicella disease. After cardiopulmonary resuscitation and stabilization, her clinical conditions didn't improve and she developed a massive pulmonary hemorrage, which led her to exitus. CONCLUSIONS: Mortality due to varicella infection is rare, but it is more common in subjects with immune deficit or chronic pathologies, and in particular age-groups. The importance of the vaccine for preventable infectious diseases is stressed in this paper, in which we present a case of death in an unvaccinated cardiopathic child with Down Syndrome affected by varicella.

Lipid profiles in a large cohort of Italian children with Down syndrome.

OBJECTIVES: Results of epidemiological studies of lipid profiles in individuals with Down Syndrome (DS) in different settings showed discordant results but laboratory norms for this population has been lacking. The aim of our study is to evaluate lipid profiles in a large population of Italian children with DS. METHODS: Lipid profiles of 357 patients with diagnosis of DS were recorded. RESULTS: Multiple linear regression was employed to estimate models for each lipid fraction as a function of sex and age in patients with DS. CONCLUSIONS: The main contribution of this paper is to provide data about lipid profile on a large cohort of people with Down syndrome. Long-term surveillance will be crucial to establish if this specific lipid profile may translate into increased morbidity and mortality from cardiovascular diseases (CVD).

Generation of switched memory B cells in response to vaccination in Down syndrome children and their siblings.

BACKGROUND: Immunodeficiency is an integral aspect of Down syndrome, as demonstrated by the increased susceptibility to infection of affected. Mortality is still higher than in general population, with respiratory infections among the major causes of death. As more people with Down syndrome are living today than ever before, it is indispensable to develop strategies to prevent and cure the associated disorders. Vaccination is the most successful instrument of preventive medicine. Special seasonal influenza and pneumococcal vaccination strategies have been designed for individuals with risk conditions of all ages. Down syndrome individuals are not included in the high-risk categories. METHODS: We enrolled in our study 15 children with Down syndrome and their siblings, vaccinated for the first time with seasonal influenza vaccine and receiving a booster dose of a glyco-conjugated pneumococcal vaccine. We compared the immunological features and response to vaccination measuring serum antibody titers and frequency of specific memory B cells. RESULTS: We confirm that a severe reduction of switched memory B cells is always associated to Down syndrome. After primary vaccination Down syndrome children generate significantly less specific switched memory B cells than their siblings. The response to a booster dose of vaccine is instead comparable in both groups. The production of specific antibodies was equally effective in Down syndrome and controls both after primary and secondary immunization. CONCLUSIONS: Down syndrome individuals should be considered a high risk group, because of their increased susceptibility to infection and reduced number of switched memory B cells. Tailored vaccination protocols are needed in order to reduce their burden of infections throughout life.

Acute monolateral proptosis and orbital myositis in a patient with discoid lupus erythematosus: a case report.

INTRODUCTION: Discoid lupus erythematosus may lead to significant orbital inflammation syndrome. Ocular manifestations related to discoid lupus erythematosus are uncommon and few cases of eye inflammation are reported. CASE PRESENTATION: A 37-year-old Caucasian woman with 5-year history of discoid lupus erythematosus presented with exophthalmos, periorbital pain and blurred vision in her right eye. Orbital computed tomography and laboratory tests were performed. Computed tomography imaging revealed an enlargement of the right medial rectus muscle. Thyroid eye disease and orbital cellulites were excluded. Corticosteroid treatment completely resolved the symptoms. CONCLUSION: This is the first case of orbital myositis in a patient with discoid lupus erythematosus presenting with acute proptosis, diplopia and single extraocular muscle involvement.