Kawasaki Disease Complicated with Cerebral Vasculitis and Severe Encephalitis.

We report a case of a 7-year-old boy with Kawasaki disease (KD) complicated with cerebral vasculitis and encephalitis. The patient was admitted with signs of encephalopathy, seizures, and coma. The diagnosis of KD was made on the 2nd day of hospitalization based on the clinical features (fever >5 days, maculopapular rash, nonpurulent conjunctivitis, fissured lips, and cervical adenopathy). Brain magnetic resonance imaging findings suggested cerebral vasculitis. Treatment with intravenous immunoglobulin was followed by mild improvement. After a single dose of immunoglobulin, pulse methylprednisolone therapy was started resulting in gradual improvement of consciousness and eventual complete motor and cognitive function recovery with regression of brain magnetic resonance lesions. KD can present with marked neurological symptomatology. Therefore, it should be considered in the differential diagnosis of encephalitis and encephalopathy etiologies in children.

Performance of the new clinical case definitions of pertussis in pertussis suspected infection and other diagnoses similar to pertussis.

BACKGROUND: In an effort to improve the pertussis diagnosis, the Global Pertussis Initiative (GPI) proposed an algorithm of the signs/symptoms of pertussis for three age groups: 0-3 months, 4 months to 9 years, and ≥10 years of age. METHODS: We evaluated the accuracy of the clinical case definitions for pertussis proposed by the GPI using laboratory-confirmed pertussis as a reference standard for four groups: clinically suspected pertussis without comorbidity; asthma exacerbation; allergic constitution, and other diagnoses (bronchitis, bronchiolitis, laryngitis, and tracheitis). We included only patients who fulfilled one or more criteria of clinical case definitions for the age groups (0-3 months, 4 months-9 years, and ≥10 years of age). The data for this prospective epidemiological study were collected between 1st January 2013-31st December 2016 at the outpatients and inpatients health care settings in the South Backa District of Autonomous Province of Vojvodina, Serbia. We evaluated accuracy of the certain sign and symptom combinations of GPI case definitions based on their sensitivity, specificity, and likelihood ratios. RESULTS: A total of 1043 participants were included, with 306 (29.3%) laboratory-confirmed pertussis cases. In patients aged 0-3 months, whoop and apnoea associated with laboratory confirmation of pertussis. In patients aged 4 months-9 years with a pertussis suspicion infection or with one of the other diagnoses, the highest accuracy was found for whoop combined with apnoea or post-tussive emesis. In patients aged 10 years and older, several different sign and symptom combinations were associated with an increased risk of pertussis among all enrolment diagnoses. There were fewer hospitalizations among the fully vaccinated children than in partly or unvaccinated children aged 4 months to 6 years (20.7% vs. 60.0%, p = 0.017). CONCLUSIONS: The numerous sign and symptom combinations in the observed case definitions were good predictors for laboratory-confirmed pertussis among all enrolment diagnoses, therefore suggesting the necessity for increased awareness of possibility for pertussis in patients with certain pertussis-like medical conditions.

Serum glutathione S-transferase Pi as predictor of the outcome and acute kidney injury in premature newborns.

BACKGROUND: The incidence of acute kidney injury (AKI) among the neonates treated at the Neonatal Intensive Care Unit is high with high mortality rates. Glutathione S-transferase (GST) class Pi plays an important role in the protection of cells from cytotoxic and oncogenic agents. The aim of the study was to examine whether the levels of serum glutathione S-transferase Pi (GST Pi) determined after birth have any predictive value for the outcome and development of AKI in premature neonates. METHODS: The prospective study included 36 premature neonates. The data about morbidity was gathered for all the neonates included in the study. The blood samples were taken in the first 6 h of life and GST Pi levels were measured. RESULTS: The mean values and standard deviations of GST Pi among the neonates who died and who survived were 1.904 ± 0.4535 vs 1.434 ± 0.444 ng/ml (p = 0.0128). Logistic regression revealed a statistically significant, positive correlation between GST Pi levels and death (p = 0.0180, OR7.5954; CI 1.4148-40.7748).The mean value of GST Pi levels in the neonates with AKI was higher than in neonates without AKI (p = 0.011). CONCLUSIONS: The conclusion of our study is that high levels of serum GST Pi in the first 6 h after birth are associated with an increased mortality and development of AKI in prematurely born neonates.

Peritoneal Dialysis in Very Low Birth Weight Neonates.

BACKGROUND: The aim of this retrospective study is to evaluate clinical characteristics and outcomes of very low birth weight (VLBW) neonates with acute kidney injury (AKI) treated with peritoneal dialysis (PD). METHODS: This retrospective study included 10 VLBW neonates treated with PD. Intravenous (IV) cannula and umbilical venous catheter were used for the peritoneal access. RESULTS: Mean age at the moment of starting PD was 14.9 ± 9.3 days. Mean body weight (BW) was 825 ± 215 g. The average gestational age was 26.3 ± 1.1 weeks. The average duration of dialysis was 20.5 ± 14.7 h. The average ultrafiltration was 7.7 ± 4.2 mL/kg/h. At the moment of starting PD, the average BW was 302 ± 317g (22 ± 13%), higher than at birth (in patients who had PD started in first 2 weeks of their lives) or higher than the BW before AKI was diagnosed (patients who had PD started when they were older than 2 weeks). The main cause of AKI was sepsis (n = 8/10). Dialysate leak was registered in 2 patients, 1 patient had peritonitis and the other had a blocked PD catheter. Six patients died during PD (severe sepsis), 1 died due to hypoxic encephalopathy and coma, and 2 patients survived. One patient (with hypoxic encephalopathy and coma) died 10 days after PD was stopped due to sepsis. The overall mortality was 80%. CONCLUSION: Acute PD is still an appropriate treatment choice for VLBW neonates with AKI. In VLBW neonates, PD can be performed with an improvised PD system and catheters.

Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome.

INTRODUCTION: In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1. METHODS: Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1. RESULTS: We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations. SUMMARY: According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19-20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of autoantibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.

Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates.

BACKGROUND: The new urinary and serum biomarkers are discovered and are being investigated. With them we can diagnose acute kidney injury (AKI) faster and more precisely and they also have a significant role in the outcome prediction. METHODS: The study included 22 extremely low-birth-weight neonates who were hospitalized in the neonatal intensive care units. They were divided into two groups based on serum creatinine (SCr) level-with and without AKI. Detection and quantification of urinary kidney injury molecule-1 (uKIM-1) was done on the third day of life, using commercially available KIM-1 rapid test. Subsequently, measurements were repeated only in subjects who were diagnosed with AKI, at different values of SCr. RESULTS: Logistic regression analysis showed that AKI is an independent risk factor for mortality. In a group of neonates with AKI, 50% of neonates administered the KIM-1 rapid test showed positive findings. KIM-1 rapid test was positive in patients with a wide range of SCr levels (range of 78.73-385 µmol/l), but all subjects had oliguria and died in the next 24 h. CONCLUSION: KIM-1 is a significant predictor of death. On the other hand, our study failed to prove that KIM-1 rapid test has any significance for early prediction of AKI.

Early biomarkers of renal injury and protective effect of erythropoietin on kidneys of asphyxiated newborn rats.

BACKGROUND: The aims of this study were to determine which of the two biomarkers of renal injury, kidney injury molecule-1 or cystatin C, is more sensitive and to evaluate whether erythropoietin protects kidneys injured by perinatal asphyxia. METHODS: Animals were split into three groups designated as follows: AE, pups that survived perinatal asphyxia and subsequently received 2.5 µg (0.1 ml) of darbepoetin-α (i.p.); A, the pups that survived perinatal asphyxia and received 0.1 ml of 0.9% NaCl; and C, control group. The pups were killed at different ages of life (6 h, 24 h, 48 h, 7 d, and 14 d of age; 10 rats in each subgroup). Immunohistopathological evaluation of kidneys was performed. RESULTS: At 48 h and on days 7 and 14, absolute injury scores were significantly lower in group AE as measured by both biomarkers. Cystatin C expression was the most intensive 6 h after the hypoxic event (average value of absolute injury score was 2.82) and declined over time. Expression of kidney injury molecule-1 was less intensive, with the average value of absolute injury score being 2.02 at 6 h and 2.105 at 24 h; the peak value (2.155) was recorded 48 h after the hypoxic event. CONCLUSION: Erythropoietin has a protective effect on hypoxic kidneys. Cystatin C is more sensitive as an early biomarker of acute kidney injury in comparison with kidney injury molecule-1.

Neuroprotective effects of hypothermia and erythropoietin after perinatal asphyxia in newborn rats.

OBJECTIVE: Evaluation of neuroprotective effects of hypothermia, erythropoietin and their simultaneous use after perinatal asphyxia in newborn rats. METHOD: Hysterectomy was performed to Wistar female rats on the last day of gestation. Perinatal asphyxia was induced by submersion of uterus containing pups in saline for 15 min. After resuscitation, pups were randomized into 4 groups, 15 animals in each: G1 - asphyxia; G2 - asphyxia + hypothermia (rectal temperature 33 °C for 1 h); G3 - asphyxia + erythropoietin (Darbepoetin-α 2.5 µg, intraperitoneally) and G4 - asphyxia + erythropoietin + hypothermia. Pups were sacrificed on 7th day of life and histopathological analysis of hippocampus was performed. RESULTS: Measure of damage to dorsal, ventral and entire hippocampus was significantly lower in groups G2, G3 and G4 than in group G1 (p ~ 0.00; respectively). Measure of damage to hippocampus in group G4 was significantly lower than in group G2 (p = 0.029). CONCLUSIONS: This study demonstrates that simultaneous use of hypothermia and erythropoietin has more expressed neuroprotective effects than sole use of hypothermia after perinatal asphyxia in newborn rats.

A case of transient hyperammonemia in the newborn transient neonatal hyperammonemia.

A case of transient hyperammonemia of the newborn (THAN) is described in this paper. THAN is the disorder that is much more frequently present than diagnosed. Therefore, it is necessary to estimate the serum ammonia level in every preterm newborn infant, who develops the signs of respiratory distress syndrome in the first hours of life, along with the symptoms of hyperammonemia (lethargy, hypotonia, seizures, and coma). Dialysis proved the most effective treatment.

Chronic inflammatory demyelinating polyradiculoneuropathy, in an 8-year-old girl, complicated by deafness and kidney fibrosis.

Based on case history and clinical and electrophysiological examinations, the authors report on a case of an 8-year-old girl who was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy. The disease was complicated by deafness and kidney fibrosis. During treatment with methylprednisolone and intravenous immunoglobulin, followed by mycophenolate mofetil, prompt improvement of neurological findings occurred. The improvement of hearing was poor. Because the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy has still not been clear, and on the grounds of several cases of chronic inflammatory demyelinating polyradiculoneuropathy conjoined with the kidney disease described in literature (glomerulopathy, interstitial nephritis), every patient with chronic inflammatory demyelinating polyradiculoneuropathy needs to undergo the urinalyses.

Idiopathic hypercalciuria associated with urinary tract infection in children.

The aim of this study was to evaluate the association between idiopathic hypercalciuria (IH) and urinary tract infection (UTI) in children. This prospective clinical study included 75 patients with UTI (without urinary tract malformations and lithiasis) and a control group of 30 healthy children. Of the total number of patients with UTI, 21% (n = 16/75) had IH, but only 7% (n = 2/30) with IH were reported in the control group (p < 0.05). Recurrent UTI affected 33% (n = 25/75) of patients , and in 67% (n = 50/75) of patients, UTI was diagnosed for the first time. In the group of patients with recurrent UTI, 44% (n = 11/25) had IH, but only 10% (n = 5/50) were reported in the group of patients with first-time UTI (p < 0.05). The results of multifactorial logistic regression analysis showed that clinical and laboratory parameters (recurrent UTI, dysuria, and microscopic hematuria) may predict the diagnosis of IH in 80% of patients and absence of IH in 87% of cases. In our opinion, IH is a major contributing factor to UTI, especially to recurrent UTI in children.