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.

Cytomegalovirus Pneumonia in a Patient with Down Syndrome.

Down syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and they represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, when causing interstitial pneumonia, associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient with DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation, and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in Streptomyces.

Pirins are evolutionarily conserved iron-containing proteins that are found in all kingdoms of life, and have been implicated in diverse molecular processes, mostly associated with cellular stress. In the present study, we started from the evidence that the insertional inactivation of pirin-like gene SAM23877_RS18305 (pirA) by ΦC31 Att/Int system-based vectors in spiramycin-producing strain Streptomyces ambofaciens ATCC 23877 resulted in marked effects on central carbon and energy metabolism gene expression, high sensitivity to oxidative injury and repression of polyketide antibiotic production. By using integrated transcriptomic, proteomic and metabolite profiling, together with genetic complementation, we here show that most of these effects could be traced to the inability of the pirA-defective strain to modulate beta-oxidation pathway, leading to an unbalanced supply of precursor monomers for polyketide biosynthesis. Indeed, in silico protein-protein interaction modeling and in vitro experimental validation allowed us to demonstrate that PirA is a novel redox-sensitive negative modulator of very long-chain acyl-CoA dehydrogenase, which catalyzes the first committed step of the beta-oxidation pathway.

Renal toxicity and chemotherapy in children with cancer.

The clinical use of antineoplastic drugs can be limited by different drug-induced toxicities. Of these, renal dysfunction may be one of the most troublesome in that it can be cumulative and in general is only partially reversible with the discontinuation of the treatment. Renal toxicity may be manifested as a reduction of the glomerular filtration rate, electrolyte imbalances, or acute renal failure. Careful assessment of renal function has to be performed taking into account that the impairment of renal function is initially silent and only later may be clinically dramatic. When clinically indicated, the reduction or, in cases of severe nephrotoxicity, the suspension of chemotherapy should be considered to avoid the progressive deterioration of the compromised glomerular and/or tubular function.

Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas.

Management of Hyperleukocytosis.

OPINION STATEMENT: Hyperleukocytosis has a high morbidity index. The involvement of the respiratory or central nervous system and the metabolic derangements accompanying tumor lysis are responsible for early mortality. Standard care for acute hyperleukocytosis must include cytoreduction, proper supportive care, and prevention of tumor lysis. Hydration, alkalization, allopurinol, or urate oxidase should be started immediately. In patients with low platelet count of less than 20,000/mm(3), platelet transfusions should be given to prevent cerebral hemorrhage, as platelets do not add substantially to blood viscosity. Packed red blood cells must be given with caution as they can significantly increase blood viscosity. If the patient is hemodynamically stable, packed red transfusions should be planned when the hemoglobin level is less than 7-8 g/dl, avoiding post-transfusional levels above 10 g/dl. Coagulation abnormalities should be corrected. Leukapheresis has been advocated to correct metabolic abnormalities and to decrease viscosity by reducing the peripheral white blood count. However, leukapheresis may fail to decrease the leukocyte count substantially or may achieve only a transient tumor bulk reduction. The procedure is generally well tolerated but can involve problems such as the need for anticoagulation or difficulty of access, and limited availability in many institutions.Specific antileukemic therapy must be initiated as soon as life-threatening complications have been corrected as it remains the first-line treatment of hyperleukocytosis.

Safe lumbar puncture under analgo-sedation in children with acute lymphoblastic leukemia.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) undergo multiple lumbar punctures (LPs) during their course of treatment for diagnostic and therapeutic purposes. LP is a stressful and painful procedure, affecting the quality of life of these children. Procedural analgo-sedation might improve the child's comfort and prevent the child's movements, reducing the risk of traumatic lumbar puncture with blasts (TLP+), mainly at diagnosis, when higher numbers of blast cells are circulating in the peripheral blood. The aim of this study was to evaluate the safety and efficacy of procedural analgo-sedation in children with ALL. METHODS: From September 2006 to November 2008, we performed a total of 252 lumbar punctures under deep sedation with propofol and ketamine in 25 children with ALL treated at our division. During the procedures, vital parameters were monitored and side effects were recorded. The efficacy of deep sedation was evaluated using Ramsay and Children's Hospital Eastern Ontario Pain scales. Cerebrospinal fluid was collected for chemical and cytological examinations. RESULTS: In all patients a satisfactory sedation and analgesia were achieved. The evaluation of vital parameters did not show any significant variation compared to baseline values. No side effects were recorded. Only 3 (1.2 %) of 252 lumbar punctures resulted in traumatic effects. CONCLUSION: To strongly improve comfort and quality of life of children with ALL and reduce the risk of TLP+ mainly at diagnosis, we recommend performing the lumbar punctures under analgo-sedation because it is a safe and effective procedure.

Bio-Composite Filaments Based on Poly(Lactic Acid) and Cocoa Bean Shell Waste for Fused Filament Fabrication (FFF): Production, Characterization and 3D Printing.

In this study, novel biocomposite filaments incorporating cocoa bean shell waste (CBSW) and poly(lactic acid) (PLA) were formulated for application in Fused Filament Fabrication (FFF) technology. CBSW, obtained from discarded chocolate processing remnants, was blended with PLA at concentrations of 5 and 10 wt.% to address the challenge of waste material disposal while offering eco-friendly composite biofilaments for FFF, thereby promoting resource conservation and supporting circular economy initiatives. A comprehensive analysis encompassing structural, morphological, thermal, and mechanical assessments of both raw materials and resultant products (filaments and 3D printed bars) was conducted. The findings reveal the presence of filler aggregates only in high concentrations of CBSW. However, no significant morphological or thermal changes were observed at either CBSW concentration (5 wt.% and 10 wt.%) and satisfactory printability was achieved. In addition, tensile tests on the 3D printed objects showed improved stiffness and load resistance in these samples at the highest CBSW concentrations. In addition, to demonstrate their practical application, several 3D prototypes (chocolate-shaped objects) were printed for presentation in the company's shop window as a chocolate alternative; while retaining the sensory properties of the original cocoa, the mechanical properties were improved compared to the base raw material. Future research will focus on evaluating indicators relevant to the preservation of the biocomposite's sensory properties and longevity.

Bilateral Tapia syndrome in teenager with post traumatic Hangman's fracture and carotid artery dissection.

Background: Tapia syndrome (TS) is a rare condition characterized by unilateral hypoglossal and recurrent laryngeal nerve palsy, leading to tongue deviation, swallowing difficulty and dysphonia. Case report: We describe a case of a 17-year-old boy who reported a bilateral TS following head and neck trauma with Hangman's fracture and right common carotid artery dissection. The confirmation occurred only after complete cognitive and motor recovery, verifying the inability to protrude the tongue and swallow, associated with complete paralysis of the vocal cords, diagnosed with fiber optic laryngoscopy.An initial recovery of tongue motility and phonation occurred after just over a month of rehabilitation. Conclusion: In addition to the lack of awareness due to the rarity of the syndrome, the diagnosis of TS may be delayed in patients who are unconscious or who have slow cognitive recovery following head trauma. The case we present may help to increase awareness and avoid unnecessary diagnostic investigations.

Phase I study of temozolomide combined with oral etoposide in children with malignant glial tumors.

The treatment of children with malignant glioma remains challenging. The aim of this multicenter phase I study is to establish the recommended dose (RD) of the combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with relapsed or refractory malignant glioma and brainstem glioma at diagnosis. A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by a classical 3 + 3 design. Cohorts of patients were enrolled at 4 different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-day courses. A total of 118 courses were administered to 18 patients with a median age of 11.2 years. At dose level 1, none displayed toxicity. Of the 6 patients at dose level 2, 1 patient had dose limiting toxicity (DLT). None of the 3 patients at dose level 3 had DLT. At dose level 4, grade III/IV thrombocytopenia and neutropenia were observed in 2 out of the 6 patients enrolled. Therefore, the MTD was established at dose level 3. The RD for phase II trial in children with malignant glial is TMZ 150 mg/m(2) for 5 days and VP-16 50 mg/m(2) for 10 days every 28 days.

Azole interactions with multidrug therapy in pediatric oncology.

Patients with cancer receive multidrug therapy. Antineoplastic agents and supportive care drugs are often administered together, leading to potential drug-drug interactions. These interactions may have significant clinical implications in terms of toxicity or a decrease in the efficacy of the treatment administered. Here, we focus on the role of azoles and their main pharmacokinetic interactions with the principal classes of drugs used in pediatric oncology. The co-administration of azoles and antineoplastic agents, corticosteroids, immunosuppressants, antacids, antiemetics, antiepileptic drugs and analgesics was investigated, and a practical guide on the management of these drugs when administered together is provided.

Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia.

BACKGROUND: Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL. METHODS: All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course. RESULTS: Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury. CONCLUSION: MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.

Fused Filament Fabrication and Computer Numerical Control Milling in Cultural Heritage Conservation.

This paper reports a comparison between the advantages and disadvantages of fused filament fabrication (FFF) and computer numerical control (CNC) milling, when applied to a specific case of conservation of cultural heritage: the reproduction of four missing columns of a 17th-century tabernacle. To make the replica prototypes, European pine wood (the original material) was used for CNC milling, while polyethylene terephthalate glycol (PETG) was used for FFF printing. Neat materials were chemically and structurally characterized (FTIR, XRD, DSC, contact angle measurement, colorimetry, and bending tests) before and after artificial aging, in order to study their durability. The comparison showed that although both materials are subject to a decrease in crystallinity (an increase in amorphous bands in XRD diffractograms) and mechanical performance with aging, these characteristics are less evident in PETG (E = 1.13 ± 0.01 GPa and σ = 60.20 ± 2.11 MPa after aging), which retains water repellent (ca = 95.96 ± 5.56°) and colorimetric (∆E = 2.6) properties. Furthermore, the increase in flexural strain (%) in pine wood, from 3.71 ± 0.03% to 4.11 ± 0.02%, makes it not suitable for purpose. Both techniques were then used to produce the same column, showing that for this specific application CNC milling is quicker than FFF, but, at the same time, it is also much more expensive and produces a huge amount of waste material compared to FFF printing. Based on these results, it was assessed that FFF is more suitable for the replication of the specific column. For this reason, only the 3D-printed PETG column was used for the subsequent conservative restoration.

From Virtual Reconstruction to Additive Manufacturing: Application of Advanced Technologies for the Integration of a 17th-Century Wooden Ciborium.

3D modelling and 3D printing techniques have become increasingly popular in different fields, including cultural heritage. In this field, there are still many challenges to overcome, such as the difficulty of faithfully reproducing complex geometries or finding materials suitable for restoration, due to the limited scientific studies. This work proposes an example of the application of advanced technologies for the reproduction of four missing columns of a 17th century polychrome wooden ciborium. The difficulties of an automatic scan due to its reflective surface (water gilding and estofado decorations) were overcome by creating a 2D manual survey and a subsequent manual 3D redrawing. The CAD model was used to print the missing elements with fused filament fabrication (FFF) in polyethylene terephthalate glycol (PETG), using the following printing parameters: nozzle 0.4 mm, infill 20%, extrusion temperature of PLA 200 °C and of PETG 220 °C, plate temperature 50 °C, printing speed 60 mm/s, layer height 0.2 mm. The conservation and restoration of the ciborium is nearing completion. This study highlights the importance of collaboration between different professionals for the correct design of a restoration, as well as the need to promote scientific research into the development of new high-performance 3D printing materials suitable for conservation.

Poly-Lactic Acid-Bagasse Based Bio-Composite for Additive Manufacturing.

Beer bagasse is a residue waste produced in great amounts; nevertheless, it is still underestimated in the industry. The aim of this paper is to develop an innovative and efficient methodology to recycle the beer bagasse by producing Poly-lactic acid(PLA)-based bio-composites, in the forms of pellets and filaments, to be used in additive manufacturing processes. To assess the suitability of beer bagasse for extrusion-based 3D printing techniques, it was, firstly, physically and chemically characterized. Then, it was added in combination with different kinds of plasticizers to PLA to make bio-composites, analyzing their thermal and physical properties. The results prove the great potential of bagasse, evidencing its printability. Both composites' pellets and filaments were used in two different 3D printing machines and the mechanical properties of the 3D-printed models were evaluated as a function of the composition and the kind of technology used. All the used plasticizers improved processability and the polymer-bagasse interface. Compared to neat PLA, no changes in thermal properties were detected, but a lowering of the mechanical properties of the 3D-printed composites compared to the neat polymers was observed. Finally, a comparison between the efficiency of the two 3D printing techniques to be used with the bio-based composites was performed.

Historically Accurate Reconstruction of the Materials and Conservation Technologies Used on the Facades of the Artistic Buildings in Lecce (Apulia, Italy).

The protection of the stone surfaces of the buildings of the city of Lecce (Apulia, Italy) represents an ancient practice, which has always allowed the conservation of the historical-artistic heritage of the city, which nowadays is an international touristic and cultural destination. The identification of ancient recipes, materials and methodologies for the protection of historical buildings plays an important role in establishing correct protocols in order to ensure the durability of stone surfaces over time. This work presents a historically accurate reconstruction of the materials and conservation technologies used on the facades of the artistic buildings in Lecce. Several historical buildings, both civil and religious, have been selected in order to investigate the treatments applied on their facades and to know the traditions spread in the past in the field of building conservation in the Salento territory. Thanks to non-invasive or micro-destructive techniques (optical microscopy, ATR-FTIR spectroscopy, pyrolysis-gas chromatography-mass spectrometry), the characteristic molecular markers of the materials and the products of degradation have been identified, deepening the knowledge of the mechanisms of deterioration and interaction between the stone material, the surface finish and the surrounding environment. The paper is a valuable tool for the knowledge of ancient traditions and the planning of proper restoration works.

A Review of Polymer-Based Materials for Fused Filament Fabrication (FFF): Focus on Sustainability and Recycled Materials.

Recently, Fused Filament Fabrication (FFF), one of the most encouraging additive manufacturing (AM) techniques, has fascinated great attention. Although FFF is growing into a manufacturing device with considerable technological and material innovations, there still is a challenge to convert FFF-printed prototypes into functional objects for industrial applications. Polymer components manufactured by FFF process possess, in fact, low and anisotropic mechanical properties, compared to the same parts, obtained by using traditional building methods. The poor mechanical properties of the FFF-printed objects could be attributed to the weak interlayer bond interface that develops during the layer deposition process and to the commercial thermoplastic materials used. In order to increase the final properties of the 3D printed models, several polymer-based composites and nanocomposites have been proposed for FFF process. However, even if the mechanical properties greatly increase, these materials are not all biodegradable. Consequently, their waste disposal represents an important issue that needs an urgent solution. Several scientific researchers have therefore moved towards the development of natural or recyclable materials for FFF techniques. This review details current progress on innovative green materials for FFF, referring to all kinds of possible industrial applications, and in particular to the field of Cultural Heritage.

Sustainable Polymer Composites Manufacturing through 3D Printing Technologies by Using Recycled Polymer and Filler.

In the last years, the excessive use of plastic and other synthetic materials, that are generally difficult to dispose of, has caused growing ecological worries. These are contributing to redirecting the world's attention to sustainable materials and a circular economy (CE) approach using recycling routes. In this work, bio-filaments for the Fused Filament Fabrication (FFF) 3D printing technique were produced from recycled polylactic acid (PLA) and artisanal ceramic waste by an extrusion process and fully characterized from a physical, thermal, and mechanical point of view. The data showed different morphological, thermal, rheological, and mechanical properties of the two produced filaments. Furthermore, the 3D objects produced from the 100% recycled PLA filament showed lower mechanical performance. However, the results have demonstrated that all the produced filaments can be used in a low-cost FFF commercial printer that has been modified with simple hand-made operations in order to produce 3D-printed models. The main objective of this work is to propose an example of easy and low-cost application of 3D printing that involves operations such as the reprocessing and the recyclability of materials, that are also not perfectly mechanically performing but can still provide environmental and economic benefits.

Feasibility study of 21-day-on/7-day-off temozolomide in children with brain tumors.

Temozolomide (TMZ) is an oral alkylating agent with proven antitumoral activity in preclinical and clinical studies in adults with high-grade glioma (HGG). However, only limited efficacy has been reported in children with HGG using the 5-day schedule. This study investigated the safety of administering TMZ to children and adolescents with brain tumors over an extended period. Extended schedules have been proven to overcome chemoresistance without any major toxicity. The toxicity of TMZ, administered at 70 mg/m(2)/day orally for 21 consecutive days every 28 days, was assessed in children with brain tumors. A total of 156 courses of TMZ were given to 17 patients (median age 12.5 years, range 1-17 years), who were recruited into the study. Eleven patients had progressive or relapsing disease, and six patients were newly diagnosed. In this cohort no cases of toxic death or nonhematological toxicity were reported. In comparison with the 5-day schedule, thrombocytopenia and neutropenia were noted to be less frequent. Grades 3 and 4 lymphopenia occurred in 10.8 and 22.4% of courses, respectively; among the lymphopenic patients there was one case of disseminated zoster (meningoencephalitis and cutaneous involvement), one case of rotavirus gastroenteritis, and two cases of herpetic stomatitis reported. The objective response rate was 11.8%. Overall, 82.3% of patients showed stable disease. The prolonged TMZ schedule appeared to be well tolerated, with few cases of neutropenia or thrombocytopenia recorded. Nevertheless, prolonged exposure to TMZ was associated with lymphopenia and may lead to a higher rate of viral infections.

Gastric adenocarcinoma presenting as thrombotic microangiopathy in a 14-year-old girl.

Gastric adenocarcinoma is rare in childhood and often presents with disseminated malignancy at diagnosis due to aspecific symptoms leading to delay in diagnosis. A familial predisposition for gastrointestinal cancer is suggested for the development of this early-onset adenocarcinoma. We report the case of a 14-year-old girl with a familial history of colorectal, liver, and breast cancers affected by metastatic gastric adenocarcinoma, who first presented with thrombotic microangiopathy. Thrombotic microangiopathy as first clinical presentation of metastatic gastric cancer is an exceptional event in childhood and represents a challenge for pediatricians. Gastric adenocarcinoma should be suspected in young patients with a significant familial history and also in the absence of initial specific signs, so as to provide correct diagnosis and appropriate treatment.