Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study.

BACKGROUND: Sepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock. METHODS: The current prospective study was conducted in the PICU of University Children's Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0-Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome. RESULTS: A total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan-Meier survival curve analysis. CONCLUSIONS: This study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Clinical and laboratory characteristics of multisystem inflammatory syndrome in children associated with COVID-19 in Egypt: A tertiary care hospital experience.

AIM: We aimed to evaluate MIS-C patients' clinical manifestations, laboratory test results and mortality outcomes in an Egyptian tertiary care university hospital. METHODS: We conducted a 12 month cross-sectional study in a tertiary-care university children's hospital. All paediatric patients (1 month to 16 years old) who met the CDC criteria for MIS-C were enrolled in the study. We assessed patients' clinical presentations, complications, treatments, imaging studies, laboratory test results and outcomes. The baseline clinical and laboratory findings of survivors and non-survivors were compared. RESULTS: Of 45 MIS-C patients, 24 (53.3%) were males, and the median (interquartile range) age was 4 (1.25-10) years. All patients had fever, 64.4% had respiratory manifestations, 48.9% presented with coma, 44.4% presented with shock, 33.3% presented with seizures, 31.1% had abdominal pain, 28.9% had vomiting and 22.2% presented with cerebrovascular stroke. A total of 15 (33.3%) patients died, and the non-survivors had a significantly higher incidence of respiratory manifestations (P = 0.028), shock (P = 0.034), cerebrovascular stroke (P = 0.043) and seizures (P = 0.044) as compared to the survivors. In addition, the serum levels of ferritin (P = 0.047), alanine aminotransferase (P = 0.047) and aspartate aminotransferase (P = 0.05) were significantly higher in the non-survivors as compared to the survivors. CONCLUSIONS: Based on our findings, MIS-C associated with COVID-19 is a potentially fatal illness. Hospitalised patients with MIS-C often have multi-organ injuries affecting the respiratory, cardiovascular, gastrointestinal and neurological systems. The deceased are more likely to exhibit respiratory manifestations, shock, cerebrovascular stroke, seizures and elevated serum levels of ferritin and liver enzymes.

Thiamine status during treatment of diabetic ketoacidosis in children - tertiary care centre experience.

OBJECTIVES: There is a lack of information regarding thiamine status in children with diabetic ketoacidosis (DKA). This study was designed to assess the thiamine status upon admission and 24 h after treatment initiation of DKA, whether newly diagnosed children or with established T1DM diagnosis, who presented with DKA. METHODS: We enrolled 90 children (mean age, 9.8 ± 2.6 years; 58 females and 32 males) with type 1 diabetes mellitus (T1DM), whether newly diagnosed or with an established T1DM diagnosis (from 1 to 5.2 years ago), who presented with DKA. We observed the initial Glasgow Coma Scale (GCS) and recovery time. The whole blood thiamine diphosphate levels were measured upon admission (baseline point) and 24 h after initiation of the DKA treatment (second-time point). RESULTS: The mean blood thiamine levels at the second-time point (90.11 ± 15.76 nmol/L) significantly decreased compared with their levels at baseline (108.8 ± 17.6 nmol/L) (p<0.001). We compared thiamine levels with the initial GCS, patient's age, and recovery time. Thiamine levels at the second-time point were positively correlated with baseline thiamine levels (r=0.86, p=0.0001) and the initial GCS (r=0.68, p=0.001) but were negatively correlated with patient's age (r=-0.61, p=0.001) and recovery time (r=-0.724, p=0.001). Based on multiple regression analysis, thiamine levels at the second-time point were directly related to the initial GCS and inversely related to the patient's age. CONCLUSIONS: The current study indicates that blood thiamine diphosphate levels significantly decreased after 24 h of DKA treatment initiation compared to pre-treatment levels. After 24 h of treatment initiation, blood thiamine levels are directly related to the initial GCS and inversely related to the patient's age.

Clinical and laboratory spectrum of inborn errors of immunity in Egypt: Five years of experience at a tertiary care university hospital.

AIM: The recognition and diagnosis of primary immunodeficiency disorders (PIDs) is challenging in developing countries. This study aimed to describe the features of PID patients in a tertiary care setting in Egypt and analyse the distribution, clinical features and outcome of PID among paediatric patients. METHODS: This cross-sectional retrospective study was conducted between January 2016 and January 2021, to evaluate all paediatric patients aged below 18 years with PID that were diagnosed according to the International Union of Immunological Societies 2017 classification. We retrospectively studied the clinical features, diagnostic spectrum, laboratory investigations and relevant immunological workup, and treatment options. RESULTS: A total of 61 PID patients were enrolled in the current study. The median age at diagnosis was 22 months. The overall consanguinity rate was 49.2%, and the family history of PID was 19.7%. Among all PIDs, the combined immunodeficiency with syndromic features predominates with 17 cases, accounting for 27.9% of all cases of PIDs. The predominant antibody deficiency was the second common PID that was diagnosed in 14 patients (23%). Recurrent pneumonia was the most common initial presentation, occurring in 77% of patients, followed by failure to thrive (63.9%), and recurrent otitis media (55.7%). The total deaths were 18 patients (29.5%). CONCLUSION: Paediatric patients with PIDs are not uncommon in Egypt. There is a need to improve PID diagnosis and treatment, for better estimation of PID and to decrease morbidity and mortality.

Assessment of Humoral Immunity to Measles Virus in Cancer Survivor Children after Chemotherapy: A Case-Control Study.

This case-control study was conducted to determine the antibody titer against the measles virus in childhood cancer survivors' post-chemotherapy treatment to determine the patient's immune status against the measles virus.We enrolled 38 children who were in complete remission and whose treatments had been stopped for at least 3 months and 38 age and sex-matched healthy controls. We analyzed the medical records of the cancer survivors, and each study participant's serum sample was analyzed by the ELISA method to determine the antibody titer against measles.The cancer survivors had significantly lower measles antibody titers than the healthy control participants, and 78.9% of cancer survivors were unprotected (seronegative) compared to 7.9% in healthy controls. After multivariate analysis, there was no statistically significant factor associated with loss of protective humoral immunity against measles.These results underline the need for post-chemotherapy measles antibody testing and revaccination of seronegative survivors.

Assessment of cystatin C in pediatric sickle cell disease and ß-thalassemia as a marker of subclinical cardiovascular dysfunction: a case-control study.

Cardiovascular complications represent the main determinant of survival in patients with hemoglobinopathies. Serum cystatin C is a well-known marker of nephropathy in sickle cell disease (SCD) and ß-thalassemia patients that has recently emerged as a strong predictor of cardiovascular dysfunction in patients with and without kidney disease. We performed a case control study to determine the role of cystatin C as a predictor of subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients. We enrolled 40 SCD patients with a mean age of 12.4 years, 40 ß-thalassemia patients with a mean age of 11.4 years and 40 age and sex-matched controls. We assessed hematological profile, serum ferritin, urinary albumin-creatinine ratio (UACR), serum cystatin C, echocardiography and carotid intima media thickness (CIMT). UACR, cystatin C and CIMT were higher in SCD and ß-thalassemia patients compared to controls (p < .001). Significantly higher cystatin C levels were observed in SCD and ß-thalassemia patients with nephropathy or left ventricular systolic dysfunction (shortening fraction <30%, or ejection fraction <55%; p < .001). Moreover, SCD patients with pulmonary hypertension had significantly higher cystatin C levels. Cystatin C levels were positively correlated with CIMT in SCD (p = .02) and ß-thalassemia patients (p < .001) while negatively correlated with ejection fraction and shortening fraction (p < .001). The cutoff values of cystatin C ≥ 16.03 and ≥ 13.2 (ng/mL) could detect subclinical cardiac dysfunction risk among SCD and ß-thalassemia patients respectively. Cystatin C appears to be a promising marker for subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients.

Clinico-laboratory profile and perforin gene mutations of pediatric hemophagocytic lymphohistiocytosis cases: a five-year single center study.

INTRODUCTION: hemophagocytic lymphohistiocytosis (HLH) is an immunological disease characterized by hemophagocytosis of blood cells and proliferation of T-cells and histiocytes in the spleen and bone marrow then infiltration into body organs. Familial HLH (FHL) is a fatal disorder and determining gene mutations is a good guide for predicting the prognosis and choosing treatment options. This study aimed to illustrate the clinical, laboratory characteristics, including perforin gene mutation screening, treatment and survival outcome of pediatric HLH patients. METHODS: we conducted this cross-sectional study on pediatric patients who were diagnosed with HLH using the revised HLH-2004 criteria, from January 2014 to February 2019 at Zagazig University Children's Hospital, Egypt. We collected demographic, clinical and laboratory data and screened for the presence of mutations in perforin (PRF1) gene by polymerase chain reaction (PCR) amplification. We treated the patients according to HLH-2004 treatment protocol and documented their survival outcome. RESULTS: the total number of cases were 18; eight males and ten females, the age range was between three months and 12 years. Of the eight HLH-2004 diagnostic criteria, all patients met at least five criteria. We detected PRF1 gene mutation in 38.9% (7 patients) with nine previously unreported mutations. Sixteen patients (88.9%) received HLH-2004 treatment protocol and the remaining two patients died before initiation of treatment. The overall mortality was 72.2% (13 patients). CONCLUSION: our results increase the awareness of clinical and laboratory characterizations of pediatric HLH patients and the prevalence of PRF1 gene mutations among those patients.

Synthesis and antioxidant evaluation of some new 3-substituted coumarins.

3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H-benzo[d][1,3]oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4-7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6-aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing of 6-aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2-aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m-anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21-23 were obtained via treatment of 2 with the corresponding o-aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.