The aim of the study was to validate the impact of the single-nucleotide polymorphism rs2413739 (T > C) in the PACSIN2 gene on thiopurines pharmacological parameters and clinical response in an ...Italian cohort of pediatric patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). In ALL, PACSIN2 rs2413739 T allele was associated with a significant reduction of TPMT activity in erythrocytes (p = 0.0094, linear mixed-effect model, multivariate analysis considering TPMT genotype) and increased severe gastrointestinal toxicity during consolidation therapy (p = 0.049). A similar trend was present also for severe hematological toxicity during maintenance. In IBD, no significant effect of rs2413739 could be found on TPMT activity, however azathioprine effectiveness was reduced in patients carrying the T allele (linear mixed effect, p = 0.0058). In PBMC from healthy donors, a positive correlation between PACSIN2 and TPMT protein concentration could be detected (linear mixed effect, p = 0.045). These results support the role of PACSIN2 polymorphism on TPMT activity and mercaptopurine adverse effects in patients with ALL. Further evidence on PBMC and pediatric patients with IBD supports an association between PACSIN2 variants, TPMT activity, and thiopurines effects, even if more studies are needed since some of these effects may be tissue specific.
Home chemotherapy programs for children with cancer are safe and feasible, and their impact on the quality of life has been reported in different countries. A home chemotherapy program was ...implemented between 2011 and 2019 in an Italian region. This pilot study investigates its safety and feasibility, along with parental satisfaction.
Patients between 0 and 18 years diagnosed with malignancy were included. Deceased patients and patients whose families moved abroad or interrupted contact with the service were excluded. Adverse events comprised immediate deterioration of the patient's condition, equipment failure, errors in drug storage, dose or patient identification and personnel safety issues. Parental satisfaction was explored through an email survey of 32 Likert-type and short open questions.
Thirty-five patients received 419 doses of intravenous chemotherapy at home (cytarabine, vincristine, vinblastine). No adverse events were reported. Twenty-three families out of 25 eligible completed the survey. Most reported being "very satisfied" with the possibility of maintaining a work/domestic routine and reducing time and financial burden of hospital access. Most were "very satisfied" with the opportunity for their child of being less troubled by the treatment. Besides, most reported being "very satisfied" with the chance for healthy siblings of maintaining their routine and coping with their brother/sister's disease. Most perceived the program as safe. All families recommended extending the program to all children in the region.
This first Italian study supports home chemotherapy as safe and effective, positively influencing the quality of life for children and their families.
Background There are no guidelines regarding enteral feeding (EF) of infants with hypoxic-ischemic encephalopathy (HIE) during and shortly after therapeutic hypothermia; consequently, clinical ...practice is, to date, still variable. The objective of this study is to assess whether a minimal EF strategy during therapeutic hypothermia may be associated with a shorter time to full EF of infants with HIE and to identify the clinical variables that independently affect the time to full EF. Methods A retrospective study, covering the period from 1 January 2015 to 30 June 2022 was performed at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, which compared infants with HIE who received minimal EF during therapeutic hypothermia with those who did not. Results Seventy-eight infants received minimal EF during therapeutic hypothermia, while 75 did not. Infants who were fed reached full EF significantly faster than those who were not. Moreover, they received parenteral nutrition and maintained central venous lines for a shorter time. A multivariate analysis, taking into account the variable of clinical severity, confirmed that minimal EF is an independent beneficial factor for reaching full EF in a shorter time and mechanical ventilation and seizures are independent factors for a longer time to full EF. Conclusions Minimal EF during therapeutic hypothermia is associated with a shorter time to full EF in stable infants with HIE. Further prospective studies are needed to better define the enteral nutrition strategy for infants during therapeutic hypothermia, regardless of the severity of clinical conditions.
Objectives
Cytomegalovirus (CMV)‐related encephalitis is a rare but potentially life‐threatening complication of CMV infection in immunocompromised patients. The high mortality rate is associated ...with deficient immune system reconstitution after hematopoietic stem cell transplant (HSCT) and poor bioavailability of antiviral drugs in cerebrospinal fluid (CSF). CMV‐related central nervous system (CNS) infection may occur with aspecific symptoms, without evidence of either blood viral load or magnetic resonance imaging (MRI) signs of encephalitis.
Methods
Here, we describe a 10‐year‐old girl who underwent an allogeneic HSCT and subsequently developed CMV encephalitis. Because of the absence of CMV antigen in the blood, the diagnosis of encephalitis was proposed only after a delay, following the onset of immune reconstitution inflammatory syndrome (IRIS). Two months of combined dual antiviral therapy with ganciclovir and foscarnet proved ineffective against CMV and caused significant bone marrow and renal toxicity. To avoid further toxicity, the girl was given daily treatment with CMV‐hyperimmune globulins alone.
Results
After three weeks, the CSF viral load dropped significantly and was undetectable within three more weeks. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery.
Conclusion
We suggest that this patient succeeded in achieving CMV CSF clearance with high dose of CMV‐hyperimmune globulin, given alone, because of the ability of immunoglobulins to penetrate the blood–brain barrier (BBB).
This case describes the high‐dose anti‐cytomegalovirus (CMV) hyperimmune globulin treatment of CMV‐induced encephalitis after allogeneic hematopoietic stem cell transplant. After two months of combined dual antiviral therapy with ganciclovir and foscarnet, the CSF viral load remained very high; meanwhile, the patient, a 10‐year‐old girl, developed severe bone marrow and renal toxicity. Complete CSF clearance was obtained with high doses of anti‐CMV hyperimmune globulins given alone. We suggest this treatment succeeded because of the ability of immunoglobulins to penetrate the blood–brain barrier.
Correspondence to Dr Irene Del Rizzo; idr8991@gmail.com A 15-day-old full-term newborn was admitted to the emergency department for right scrotal swelling, irritability and poor feeding that started ...12 hours earlier, without fever or vomiting. Newborns have a 3%–16% risk of incarceration, which rises up to 31% in preterm infants.1 Amyand hernia with appendicitis is a sporadic event (0.1%), and it is possibly due to the incarceration of the appendix into the herniary sac.2–4 Although rare, it should be considered in newborns with incarcerated hernia since early perforation and peritonitis are quite frequent in neonatal appendicitis. ...a delayed diagnosis can be life threatening.5 The authors would like to thank Martina Bradaschia, MD, for the English revision of the manuscript. Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme 1.
The disease is typically expressed when fructose- and ...sucrose-containing foods are first introduced in the diet; acute manifestations include nausea, vomiting, abdominal distress, and symptomatic hypoglycemia 1,2. Chronic fructose ingestion eventually leads to poor feeding, growth retardation and gradual liver and/or renal failure 3,4. Some patients may remain undiagnosed until adulthood because of a self-protective avoidance of sweet tasting food that prevents the development of acute toxicity from fructose containing food; however, these subjects may suffer intermittent symptoms throughout life, leading to potentially serious misdiagnosis 4.
We report the case of a patient with unrecognized hereditary fructose intolerance in which chronic gastrointestinal complaints, low body weight, and unexplained food avoidance were addressed as manifestations of an eating disorder during adolescence.
While hematological symptoms are considered difficult to manage in a Pediatric Palliative Care setting, home may still represent a safe and convenient place for transfusions in patients with advanced ...malignancy or chronic conditions. This research focuses on the safety and feasibility of a home transfusion program.
This is a case series of patients between 0 and 18 years diagnosed with advanced malignancy or incurable chronic conditions and eligible to Pediatric Palliative Care who received home platelet or packed red cell transfusions. For all patients, we recorded adverse events such as acute hemolytic reactions, allergic reactions, or any emergency condition requiring hospital admission, equipment failure, blood product transport or storage errors, errors in patient identification, and personnel safety issues. We explored parental satisfaction with a Likert-type questionnaire and short open questions.
We reviewed 101 transfusion procedures for six patients in Pediatric Palliative Care performed by the Regional Pediatric Palliative Care network between 2014 and 2020. We did not report any adverse effects. Families reported satisfaction and a sense of safety and positively evaluated the opportunity of having transfusion at home to minimize the disruption in everyday life. The cost analysis resulted in a consistent saving for the Regional Health System.
This study supports the safety and feasibility of home transfusion in Pediatric Palliative Care.
Sleep disturbance is a crucial issue in pediatric palliative care, with a dramatic impact on the quality of life of children and families. Dexmedetomidine (DEX) is a selective α-2 agonist, with ...anxiolytic, hypnotic, and analgesic properties, that could play a role in the management of refractory sleep disturbances. We describe the use of intranasal DEX as a sleep inductor in a 10-year-old female with dystrophic epidermolysis bullosa and a severe sleep disorder. After treatment with melatonin, benzodiazepines, and niaprazine had failed, she was admitted to the hospital where 3 mcg/kg/day of intranasal DEX was administered before bedtime. She received 0.7 mL of the IV formulation at a concentration of 100 mcg/mL with half the dose given in each nostril via a Mucosal Atomization Device. During this time, she was also monitored for potential side effects (e.g., bradycardia, blood pressure derangements). After 2 weeks of hospitalization, she was discharged with ready-to-use doses of DEX for home treatment. The child's heart rate and blood oxygen saturation were monitored at home. There was a definite improvement in sleep quality and duration, daytime alertness, pain control, and quality of life. No side effects were reported and the drug retained its effect over time (the patient is currently taking the drug). Intranasal DEX could be a safe and effective strategy to manage refractory sleep disturbances in children in pediatric palliative care.
OBJECTIVESCytomegalovirus (CMV)-related encephalitis is a rare but potentially life-threatening complication of CMV infection in immunocompromised patients. The high mortality rate is associated with ...deficient immune system reconstitution after hematopoietic stem cell transplant (HSCT) and poor bioavailability of antiviral drugs in cerebrospinal fluid (CSF). CMV-related central nervous system (CNS) infection may occur with aspecific symptoms, without evidence of either blood viral load or magnetic resonance imaging (MRI) signs of encephalitis. METHODSHere, we describe a 10-year-old girl who underwent an allogeneic HSCT and subsequently developed CMV encephalitis. Because of the absence of CMV antigen in the blood, the diagnosis of encephalitis was proposed only after a delay, following the onset of immune reconstitution inflammatory syndrome (IRIS). Two months of combined dual antiviral therapy with ganciclovir and foscarnet proved ineffective against CMV and caused significant bone marrow and renal toxicity. To avoid further toxicity, the girl was given daily treatment with CMV-hyperimmune globulins alone. RESULTSAfter three weeks, the CSF viral load dropped significantly and was undetectable within three more weeks. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery. CONCLUSIONWe suggest that this patient succeeded in achieving CMV CSF clearance with high dose of CMV-hyperimmune globulin, given alone, because of the ability of immunoglobulins to penetrate the blood-brain barrier (BBB).
PDF
