Immune Response to SARS-CoV-2 Infections in Children with Secondary Immunodeficiencies.

BACKGROUND AND PURPOSE: It is a matter of research, whether children with immunodeficiencies are able to generate an effective immune response to prevent SARS-CoV-2 reinfection. This study aimed to evaluate and compare the seroconversion rates and changes of lymphocyte subsets during COVID-19 in immunocompetent children and those with secondary immunodeficiencies. METHODS: In 55 children - 28 immunocompromised and 27 immunocompetent - hospitalized with confirmed SARS-CoV-2 infection, the level of IgG antibodies against the Spike protein was determined on two to three occasions. In those children from the study group whose immunosuppressive treatment did not alter during the study (n = 13) and in selected children from the control group (n = 11), flow cytometric evaluation of lymphocyte subsets was performed twice - 2 weeks and 3 months post-infection. RESULTS: Seroconversion reached 96.3% in both studied groups; however, the immunocompromised cohort achieved lower titers of detectable anti-S antibodies. There was no correlation between seroconversion or titers of antibodies and the total number of lymphocytes or their subsets. In the immunocompetent cohort, we reported a significant decrease in NK cells during the infection. In this group and the entire study population, a positive correlation was noticed between the CD4 + /CD8 + T cell ratio and the severity of COVID-19 pneumonia. CONCLUSIONS: Children with secondary immunodeficiencies seroconvert in equal percentages but with a significantly lower titer of anti-S antibodies compared to their immunocompetent peers. The lower number of NK cells in the immunocompetent cohort may result from their participation in antiviral immunity, whereas reduced CD4 + /CD8 + T cell ratios among immunocompromised children may be a protective factor against a severe COVID-19.

Long-COVID in immunocompromised children.

Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child's general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children - 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%). Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%). CONCLUSIONS: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings. WHAT IS KNOWN: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 - mainly mild or asymptomatic - among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups. WHAT IS NEW: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.

Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations.

BACKGROUND: Infantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy. DESIGN: Forty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography. RESULTS: IH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2-34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15-105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject. CONCLUSIONS: Subjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.

BCG Moreau Vaccine Safety Profile and NK Cells-Double Protection Against Disseminated BCG Infection in Retrospective Study of BCG Vaccination in 52 Polish Children with Severe Combined Immunodeficiency.

OBJECTIVES: The aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients. MATERIAL: The profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children's Memorial Health Institute, Warsaw (CMHI), in the years 1980-2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134-1141). RESULTS: Significantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study-119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with T-B+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided. CONCLUSION: The BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients' survival and the fact that they protect against BCG infection.

Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO2). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a "hypoventilation" might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Nutritional therapy complications in children with ultra-short bowel syndrome include growth deficiency but not cholestasis.

AIM: Children with ultra-short bowel syndrome (USBS) have not been extensively studied to date because the condition is rare. The aim of the study was to assess the nutritional status of children with USBS receiving home parenteral nutrition, using citrulline serum concentration and cholestasis. METHODS: We studied 17 patients with USBS, with a median age of 6.6 years and median duration of parenteral nutrition of 6.6 years. The study was carried out at The Children's Memorial Health Institute, Warsaw, from January 2014 to January 2015. RESULTS: The median standard deviation score (SDS) was -1.2 for body mass according to chronological age, -1.72 according to height and -0.59 according to height for age. Patients requiring seven days per week parenteral nutrition had a citrulline concentration below 10 µmol/L. Decreased bone-mineral density was observed in 87% of the patients. Low values of 25-hydroxyvitamin D were found in 53% of the children. None of the patients had elevated conjugated bilirubin levels above 34.2 µmol/L. CONCLUSION: Children with USBS were growth deficient according to their chronological age, with frequent abnormal bone mineralisation and vitamin D deficiency. Children requiring parenteral nutrition seven days a week had citrulline concentrations below 10 µmol/L. Cholestasis was not seen.

Eosinophilic cystitis and cholangitis - systemic disease triggered by mycobacterium tuberculosis?

Eosinophilic cystitis (EC) is a rare inflammatory disorder of the urinary tract characterized by infiltration of bladder with eosinophils. The cause remains unclear, immunological mechanisms have been implicated in pathogenesis. Potential etiological factors include: tumors, allergy, parasitic infections, trauma. The disease may have a variable course, from a mild self-limiting, through common symptoms like: dysuria, hematuria, abdominal pain, tumor, to severe renal failure, with eosinophilic infiltration of the other organs and systemic complications. Treatment depending on disease severity and etiology is pharmacological and/or surgical. Here we report a case of a previously healthy 16-year old girl with inflammatory tumor in the liver hilum infiltrating extrahepatic biliary tract who developed three months later haematuria with acute dysuric signs and renal failure. Based on histopathological findings diagnosis of eosinophilic cystitis was established. Tests for Mycobacterium tuberculosis were positive. To our knowledge, EC association with cholangitis and tuberculosis have never been reported before.

Eosinophilic cystitis and cholangitis - systemic disease triggered by mycobacterium tuberculosis?

Eosinophilic cystitis (EC) is a rare inflammatory disorder of the urinary tract characterized by infiltration of bladder with eosinophils. The cause remains unclear, immunological mechanisms have been implicated in pathogenesis. Potential etiological factors include: tumors, allergy, parasitic infections, trauma. The disease may have a variable course, from a mild self-limiting, through common symptoms like: dysuria, hematuria, abdominal pain, tumor, to severe renal failure, with eosinophilic infiltration of the other organs and systemic complications. Treatment depending on disease severity and etiology is pharmacological and/or surgical. Here we report a case of a previously healthy 16-year old girl with inflammatory tumor in the liver hilum infiltrating extrahepatic biliary tract who developed three months later haematuria with acute dysuric signs and renal failure. Based on histopathological findings diagnosis of eosinophilic cystitis was established. Tests for Mycobacterium tuberculosis were positive. To our knowledge, EC association with cholangitis and tuberculosis have never been reported before.

Cerebrospinal fluid eosinophilia in a child with neuroborreliosis.

Cerebrospinal fluid eosinophilia is rare and usually associated with eosinophilic meningitis caused by helminthic infections. It is also observed in bacterial or fungal meningitis (syphilis, tuberculosis, coccidioidomycosis), in patients with malignancies, ventriculoperitonial shunts, hypereosinophilic syndrome or allergy to some medications. Here we present a case of an 8-year-old boy admitted with fever and clinical signs of meningitis. Cerebrospinal fluid (CSF) analysis showed marked eosinophilia. Basing on further serological CSF testing the diagnosis of borreliosis was established. Cerebrospinal fluid eosinophilia in Borrelia burgdorferi infection has never been reported before.

Candidaemia in a Polish tertiary paediatric hospital, 2000 to 2010.

Data on the epidemiology of invasive Candida infections in paediatric patients in Europe are still limited. The aim of this retrospective study was to analyse the epidemiology of candidaemia in a tertiary paediatric hospital in Poland from 2000 to 2010. Using microbiological records, a total of 118 episodes of candidaemia were identified in 114 children, with an annual incidence of 0.35 episodes/1000 discharges. The highest incidences were found in the medical intensive care unit (5.28), and in neonatal intensive care (1.47). The mortality rate was 8.5%. Candida albicans and C. parapsilosis were the most prevalent species (39.8% and 35.6% respectively). The prevalence of non-albicans species increased from 12.5% in 2000 to 70% in 2010. No differences were found between C. albicans and C. non-albicans episodes in terms of demographics, risk factors or mortality. The highest resistance rates (overall 7.6%) were observed for fluconazole (4.3% in C. albicans, 7.1% in C. parapsilosis and 13.8% in other Candida species). Resistance to amphotericin B (2.5%) was limited to non-albicans isolates. The dynamic changes in species distribution and increasing resistance of fungal pathogens confirm the importance of epidemiological surveillance.

Does long term parenteral nutrition in children have an impact on malocclusion? Preliminary report.

AIM: To evaluate the impact of long-term partial parenteral nutrition and its complications on malocclusion in children and adolescents. MATERIAL AND METHODS: The assessment involved 61 patients (2.25 to16 years of age) without a masticatory parafunction - i.e. 31 subjects receiving parenteral nutrition for a mean period of 5.71±2.87 years, and 30 healthy control subjects. The medical records provided information on the delivery (full-term, preterm), birth body mass, Apgar score, weight deficiency at the age of 1 year; the patient assessment included the current body mass, the number of enteral meals per day and parenteral meals per week, occlusion (acc.to Orlik-Grzybowska's parameters). The statistical analysis was performed by using the chi-square test, Spearman's correlation analysis; the statistical significance was p<0.05. RESULTS: Premature infants with low birth body mass (38.7%), Apgar score below 7 (25.8%), underweight in the first year of life (74.2%) and on examination day (58.1%) were only part of the test group. Mean number of eaten meals: 4.63±1.88 in parenteral nutrition patients, 6.26±1.39 in healthy individuals in the control group. Malocclusions were significantly more frequent in the children receiving parenteral nutrition (38.71%: the most frequent defects included crossbite (19.31%), open bite malocclusion (12.9%), crowding of teeth (9.67%), than in the control group (13.3%: crossbite (3.3%), open bite malocclusion (3.3), crowding of teeth (3.3%). A correlation was statistically proved between the malocclusion and parenteral nutrition, the number of parenteral feeding sessions per week, the current low body mass. CONCLUSION: Long-term parenteral nutrition, a decreased number of oral meals and a coexistent low body mass at the developmental age may contribute to the development of malocclusion.

Evaluation of Arsenic and Cobalt Levels in Pediatric Patients Receiving Long-Term Parenteral Nutrition.

This study continues the research in which we determined the concentration of aluminum in children receiving long-term parenteral nutrition (LPN). Since our results were interesting, we decided to assay arsenic (As) and cobalt (Co) in the collected material, which, like aluminum, constitute contamination in the mixtures used in parenteral nutrition. Excesses of these trace elements in the human body are highly toxic, and deficiencies, particularly in the case of Co, can lead to various complications. The aim of this study was to determine the impact of LPN in children on their serum levels of As and Co, as well as the excretion of these elements in urine, and to compare them with a control group of healthy children. The study group consisted of 83 children receiving home parenteral nutrition from two Polish centers, while the control group included 121 healthy children. In both groups, the levels of As and Co in serum and urine were measured. The elemental compositions of the samples were determined using inductively coupled plasma mass spectrometry (ICP-MS). It was demonstrated that the children receiving LPN did not have increased As exposure compared to the controls. Greater exposure compared to the control group was shown for Co. In conclusion, children receiving LPN are not exposed to As, and even though the concentrations of Co in serum and urine were higher in the LPN group than in the healthy controls, neither trace element poses a health threat to children requiring LPN.

Managing Undernutrition in Pediatric Oncology: A Consensus Statement Developed Using the Delphi Method by the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology.

"Managing Undernutrition in Pediatric Oncology" is a collaborative consensus statement of the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology. The early identification and accurate management of malnutrition in children receiving anticancer treatment are crucial components to integrate into comprehensive medical care. Given the scarcity of high-quality literature on this topic, a consensus statement process was chosen over other approaches, such as guidelines, to provide comprehensive recommendations. Nevertheless, an extensive literature review using the PubMed database was conducted. The following terms, namely pediatric, childhood, cancer, pediatric oncology, malnutrition, undernutrition, refeeding syndrome, nutritional support, and nutrition, were used. The consensus was reached through the Delphi method. Comprehensive recommendations aim to identify malnutrition early in children with cancer and optimize nutritional interventions in this group. The statement underscores the importance of baseline and ongoing assessments of nutritional status and the identification of the risk factors for malnutrition development, and it presents tools that can be used to achieve these goals. This consensus statement establishes a standardized approach to nutritional support, aiming to optimize outcomes in pediatric cancer patients.

Neutrophil functions in patients with neutropenia due to glycogen storage disease type 1b treated with empagliflozin.

ABSTRACT: Neutropenia and neutrophil dysfunction in glycogen storage disease type 1b (GSD1b) are caused by the accumulation of 1,5-anhydroglucitol-6-phosphate in granulocytes. The antidiabetic drug empagliflozin reduces the concentration of 1,5-anhydroglucitol (1,5-AG), thus restoring neutrophil counts and functions, leading to promising results in previous case reports. Here, we present a comprehensive analysis of neutrophil function in 7 patients with GSD1b and 11 healthy donors, aiming to evaluate the immediate (after 3 months) and long-term (after 12 months) efficacy of empagliflozin compared with the reference treatment with granulocyte-colony stimulating factor (G-CSF). We found that most patients receiving G-CSF remained neutropenic with dysfunctional granulocytes, whereas treatment with empagliflozin increased neutrophil counts and improved functionality by inhibiting apoptosis, restoring phagocytosis and the chemotactic response, normalizing the oxidative burst, and stabilizing cellular and plasma levels of defensins and lactotransferrin. These improvements correlated with the decrease in serum 1,5-AG levels. However, neither G-CSF nor empagliflozin overcame deficiencies in the production of cathelicidin/LL-37 and neutrophil extracellular traps. Given the general improvement promoted by empagliflozin treatment, patients were less susceptible to severe infections. G-CSF injections were therefore discontinued in 6 patients (and the dose was reduced in the seventh) without adverse effects. Our systematic analysis, the most extensive reported thus far, has demonstrated the superior efficacy of empagliflozin compared with G-CSF, restoring the neutrophil population and normal immune functions. This trial was registered as EudraCT 2021-000580-78.

[Secondary hemophagocytic syndromes]. / Wtórne zespoly hemofagocytarne--aktualny problem interdyscyplinarny.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening extreme whole body inflammatory state. It results from the pathological hyperactivation of the immune system, because of congenital or acquired abnormalities of cytotoxicity and NK or T cells. Uncontrolled stimulation of lymphocytes and macrophages lead to hypercytokinemia, organ infiltration by these cells and multiple organ failure. There are genetic HLH and secondary HLH, associated with infections, autoimmune disorders, malignancies. The frequency of the secondary form is difficult to estimate because of the wrong and difficult diagosis. The clinical course is often insidious and nonspecific. Symptoms are varied. The most important are: unremitting fever, hepatosplenomegaly. Generalized edema, rash, lymphadenopathy may occur. Liver failure, respiratory, circulatory and multiple organ failure could develop in a very short time. Most common abnormalities in additional tests are: cytopenias, hypofibrinogenaemia, hypertriglyceridaemia, hyperferritinaemia, hypertransaminasaemia, elevated parameters of inflammation (excepting lowering erythrocyte sedimentaion rate). Criteria for diagnosis and therapeutic protocols referto the genetic forms of HLH. Currently, there are no guidelines for secondary HLH. Diagnostic and therapeutic difficulties also arise from clinical picture, similar as in the systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome. We present the clinical presentation, diagnostic pitfalls and treatment of secondary HLH, based on a review of the current literature and our own observations.

Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case.

Unexpected Serum and Urine Aluminum Concentrations in Pediatric Patients on Home Parenteral Nutrition.

The intravenous supply of aluminum (Al) present in parenteral nutrition solutions poses a high risk of the absorption of this element, which can result in metabolic bone disease, anemia, and neurological complications. The aim of this study is to determine the impact of long-term parenteral nutrition (PN) in children on serum Al concentration and its urinary excretion compared to healthy children. We evaluated serum Al concentrations and its urinary excretion in patients enrolled in the Polish home parenteral nutrition (HPN) program between 2004 and 2022. The study group included 83 patients and the control group consisted of 121 healthy children. In children whose PN was started in the neonatal period, we found higher serum Al concentrations and higher urinary Al excretion than in other subjects whose PN was started later. Only 12% of the children on chronic parenteral nutrition had serum Al concentrations of less than 5 µg/L. Healthy children in the control group had higher serum Al concentrations than those in the parenteral nutrition group, which may indicate the influence of one's environment and diet on Al serum levels.

S100B Protein but Not 3-Nitrotyrosine Positively Correlates with Plasma Ammonia in Patients with Inherited Hyperammonemias: A New Promising Diagnostic Tool?

Individuals with inherited hyperammonemias often present developmental and intellectual deficiencies which are likely to be exaggerated by hyperammonemia episodes in long-term outcomes. In order to find a new, systemic marker common to the course of congenital hyperammonemias, we decided to measure the plasma level of S100 calcium-binding protein B (S100B), which is associated with cerebral impairment. Further, we analyzed three mechanistically diverged but linked with oxidative-nitrosative stress biochemical parameters: 3-nitrotyrosine (3-NT), a measure of plasma proteins' nitration; advanced oxidation protein products (AOPP), a measure of protein oxidation; and glutathione peroxidase (GPx) activity, a measure of anti-oxidative enzymatic capacity. The plasma biomarkers listed above were determined for the first time in congenital hyperammonemia. Also, the level of pro- and anti-inflammatory mediators (i.e., IL-12, IL-6, IL-8, TNF-α, IL-1ß, and IL-10) and chemokines (IP-10, MCP-1, MIG, and RANTES) were quantified. S100B was positively correlated with plasma ammonia level, while noticeable levels of circulating 3-NT in some of the patients' plasma did not correlate with ammonia concentration. Overall, the linear correlation between ammonia and S100B but not standard oxidative stress-related markers offers a unique perspective for the future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias. The S100B measure may support the development of therapeutic targets and clinical monitoring in these disorders.

Home enteral nutrition in children--2010 nationwide survey of the Polish Society for Clinical Nutrition of Children.

Published epidemiologic data on the administration rates of enteral/parenteral home nutrition is very limited. The aim of this first nationwide study was to assess the availability of pediatric home enteral nutrition (HEN) services in Poland. The questionnaire was sent to all regional centers providing pediatric HEN services in Poland (n = 14). The analysis included the number of pediatric patients who received HEN in 2010, their demographic characteristics and geographical distribution. Furthermore, the distributions of indications and methods of enteral nutrition administration were analyzed, along with the reasons of withdrawal from the HEN program. The number and fraction of children receiving HEN increased in 2010, from 433 (11.34 per 1 million inhabitants) on January 1st to 525 (13.75) on December 31st. Marked differences were observed in geographical distribution of this parameter, from zero to up to 30 pediatric patients per 1 million inhabitants. Median age of patients was 6 years (range: 9 months-18 years). In most cases, HEN was prescribed due to neurological disorders (n = 337, 64.2%), and administered by means of gastrostomy (n = 450, 85.71%). This study revealed the dynamic development of pediatric HEN services in Poland but also documented their potential regional shortages.

Different Course of SARS-CoV-2 Infection in Two Adolescents With Other Immunosuppressive Factors.

Even after two years of the Coronavirus Disease 2019 (COVID-19) pandemic, despite known risk factors, we are still unable to predict the severity of the infection in specific patients. Due to the contradictory data, the protective role of immunosuppression in preventing the severe course of the infection remains uncertain. Therefore, we want to discuss the influence of several immunosuppressive factors on the COVID-19 pattern in children, based on two case reports regarding 17-year-old boys with other immunosuppressive factors and a completely different course of the disease. The first patient suffered from AIDS, syphilis and primary central nervous system B-cell lymphoma, treated with radiotherapy. He experienced a light path of the infection, presenting only periodically appearing cough with no X-ray inflammatory changes. Nevertheless, due to the risk of severe COVID-19 and transient hypoxia, remdesivir was administered. He remained in a generally good condition and his follow-up did not reveal any noticeable complications. The second patient was characterised by Down syndrome, obesity, polyarteritis nodosa and chronic immunosuppressive therapy. He developed massive pneumonia, required treatment in the intensive care unit with the use of mechanical ventilation, remdesivir and anakinra. Despite the initial improvement of his general condition, including the degree of lung involvement and respiratory function, he developed an intracerebral haemorrhage, leading to brain herniation and ultimately death. In conclusion, HIV infection, oncological and immunosuppressive treatment do not seem to predispose to the severe course of COVID-19, whereas Down syndrome and obesity do.