Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies.

BACKGROUND: Septic acute kidney injury (AKI) accounts for more than half of all cases of AKI in critically ill children. The renal histology was found to alter the management in more than two-third of cases of adult acute renal failure. Better insight into the pathogenesis of pediatric septic AKI could be based on developing a clearer appreciation of the histopathological changes. No comprehensive study of the histopathological features of septic AKI in critically ill children has yet been performed. METHODS: This retrospective observational study was conducted at a level-III pediatric intensive care unit (PICU) from June 2013 to July 2014. Children (<13 years of age) who had expired due to sepsis and AKI and had post-mortem renal biopsies were included. Sepsis and AKI were defined according to the International pediatric sepsis consensus conference and Acute Kidney Injury Network (AKIN) definition and classification system, respectively. RESULTS: A total of 708 patients were admitted to the PICU during the study period, with mortality of 24 % (n = 170) and 62 complete data of post-mortem renal biopsies were included. The median (IQR) age was 12 (4.8-36) months, pediatric risk of mortality score (PRISM) III was 14 (12-18) and the time to biopsy after death was 24 (18-26) minutes. Normal histology was the most common change 41.9 % (n = 26), followed by acute tubular necrosis (ATN) 30.6 % (n = 19). A combination of changes involving tubules, glomeruli, interstitium, and blood vessels was noted in 21 % (n = 13) of the specimens. Eight percent (n = 5) of the specimens had features consistent with thrombotic microangiopathy. Normal histology was noted in 15.4 % (n = 4/26), 50 % (n = 13/26), and 34.6 % (n = 9/26) of AKI stage-I, II, and III, respectively. CONCLUSION: The most common renal histopathological change in septic AKI in critically ill children was normal histology followed by ATN.

SERUM LEVELS OF COPPER AND IRON IN DENGUE FEVER.

The role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

Culture proven Salmonella typhi co-infection in a child with Dengue fever: a case report.

Infectious diseases are one of the major causes of morbidity and mortality in developing countries. Sometimes concurrent infections with multiple infectious agents may occur in one patient, which make the diagnosis and management a challenging task. The authors here present a case of co-infection of typhoid fever with dengue fever in a ten-year-old child and discuss the pertinent issues. The authors emphasize that the risk factors predicting the presence of such co-infections, if developed, will be immensely useful in areas where dengue outbreak occurs in the background of high transmission of endemic infections.

Serum levels of copper and iron in dengue fever / Níveis séricos de cobre e ferro na dengue

SUMMARYThe role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

RESUMOO papel dos elementos-traço na virulência da dengue não é ainda conhecido. O presente estudo avaliou os níveis séricos de dois micronutrientes, cobre e ferro, em casos de dengue. O estudo envolveu 96 pacientes dos quais 48 apresentavam dengue grave ou não grave (com ou sem sinais de alerta), e outros 48 pacientes com outras doenças febris (OFI) representaram os controles. Níveis séricos de cobre e ferro foram avaliados na admissão e no momento da defervescência usando kits comerciais disponíveis. À admissão, nenhuma diferença nos níveis séricos de cobre foi observada entre casos e controles. No grupo com dengue, os níveis de cobre se encontravam significativamente reduzidos nos casos graves e não graves com sinais de alerta, em comparação aos casos não graves sem sinais de alerta. Contrariamente, no momento da defervescência os níveis de cobre se encontravam aumentados em todos os casos de dengue em relação aos controles com outras doenças febris (OFI), no entanto, nenhuma diferença foi observada entre os casos de dengue. Diferentemente dos pacientes com outras doenças febris, os casos de dengue mostraram um padrão de elevação dos níveis de cobre do dia da admissão até a defervescência. Por outro lado, estas diferenças não foram observadas em relação aos níveis de ferro entre os dois grupos, com exceção de níveis de ferro reduzidos encontrados nos casos graves, em comparação aos não graves com sinais de alerta. Os resultados mostram que o cobre está associado à gravidade da dengue e esta observação enfatiza a necessidade de investigação do envolvimento de elementostraço na gravidade da doença para melhorar o prognóstico da dengue.

Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial.

PURPOSE: Ventilator associated pneumonia (VAP) is one of the most common nosocomial infections in the pediatric intensive care unit (PICU). It is associated with increased mortality and prolonged hospital stay. Several preventive strategies have been introduced to reduce VAP. One novel intervention is prophylactic administration of probiotics. Studies on the effect of probiotics on VAP in pediatric populations are lacking. METHODS: This was an open-label randomized controlled trial. A total of 150 children no older than 12 years admitted to the PICU were recruited from November 2011 to July 2013. Children who were likely to require ventilation for more than 48 h were eligible for inclusion in the study. Patients were randomized into two groups after stratification based on age groups. Children in the intervention group received probiotic preparation twice a day beginning from the day of ICU admission till 7 days or discharge from ICU, whichever was earlier. The control group did not receive any placebo. Children were examined daily for evidence of VAP and were followed up till discharge from hospital. Incidence of VAP, duration of hospital stay, and mortality were compared. RESULTS: Children who received prophylactic probiotics had a lower incidence of VAP compared to the control group (17.1 % in the probiotics group vs 48.6 % in the control group, p < 0.001; 22 per 1,000 ventilated days vs 39 per 1,000 ventilated days, p = 0.02). On multiple logistic regression analysis, use of prophylactic probiotics decreased the incidence of VAP by 77 % and reduced the duration of ICU and hospital stays by an average of 2.1 and 3.3 days, respectively, after adjusting for the other confounders. No complications due to administration of probiotics were observed in the study. CONCLUSION: Prophylactic probiotics administration resulted in reduction of the incidence of VAP in critically ill children in a setting where baseline VAP rates are high. The intervention was found to be safe.

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study.

BACKGROUND: Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world. OBJECTIVES: The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years. MATERIALS AND METHODS: In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded. RESULTS: The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI. CONCLUSIONS: Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.

Haemolytic uraemic syndrome associated with Pseudomonas aeruginosa sepsis.

Haemolytic uraemic syndrome (HUS) is a recognized complication of infection with Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae type 1. Infections with other micro-organisms, especially Streptococcus pneumoniae, have been cited as causes of HUS. In addition, influenza virus and other viruses may rarely be associated with this syndrome. A 2-year-old girl presented with severe Pseudomonas aeruginosa sepsis with renal failure and ecthyma gangrenosum. Further investigations revealed features of HUS. She was managed with antibiotics and other supportive measures including peritoneal dialysis, and subsequently made a full recovery. A possible role of neuraminidase in the pathogenesis of P. aeruginosa-associated HUS was proposed. This is the first reported case of P. aeruginosa sepsis leading to HUS.

Incidence and etiology of acute kidney injury in southern India.

OBJECTIVES: To determine the incidence, etiology, short term outcome and predictors of mortality in hospitalized children aged 1 mo to 13 y with Acute Kidney Injury (AKI). METHODS: This prospective observational study was conducted in the pediatric wards and the pediatric intensive care unit (PICU) of a tertiary hospital in southern India, to study the clinico-etiological profile of AKI (defined according to the Acute Kidney Injury Network criteria). From June 2010 through March 2011, 2376 children were included in the study. RESULTS: The incidence of AKI was 5.2 % in the pediatric wards and 25.1 % in the PICU. AKI occurred in association with infections (55.4 %), acute glomerulonephritis (16.9 %), cardiac disease (4.8 %), envenomations (4.2 %) and hemolytic uremic syndrome (3.6 %). Pneumonia constituted 26.1 % of the infections. Tropical febrile illnesses (dengue, scrub typhus, enteric fever, cholera, tuberculosis, malaria and leptospirosis) constituted 15.6 % of children with AKI. Dialysis was required in 14.5 % of patients; mortality was 17.5 %. A significant proportion of children (17.5 % of survivors) had partial renal recovery at discharge. On multivariate logistic regression, dysnatremia and meningoencephalitis were independent predictors of mortality in AKI. CONCLUSIONS: The incidence of AKI is high in the patient population, including the non-critically ill children. AKI continues to be associated with adverse outcomes. Presence of dysnatremia and meningoencephalitis are poor predictors of outcome in AKI.

Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange.

A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2 months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12 months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.

Scrub typhus in children at a tertiary hospital in southern India: clinical profile and complications.

OBJECTIVE: To study the clinical profile of and complications in children with scrub typhus. DESIGN: Prospective observational study. SETTING: Tertiary care hospital. METHODS: Children up to 12 years of age who had a fever for more than five days without an identifiable infection were included. All children who were suspected of having rickettsial infections were defined as having scrub typhus if they had a positive Weil-Felix test result (OX-K 1:80 or more) and one or more of the following clinical features (after exclusion of other diagnoses): rash, edema, hepatosplenomegaly, lymphadenopathy, an eschar, and a tick bite or tick exposure. RESULTS: Thirty-five children were diagnosed with scrub typhus between February 2010 and February 2011. The age of the patients ranged from 1.5 to 12 years. Edema, crackles/rhonchi, hepatomegaly and hypotension were encountered in 60%, 23%, 91% and 34% of patients, respectively. An eschar was observed in 11% of the cases. Complications included myocarditis with cardiogenic shock in 34% of the cases and acute kidney injury in 20% of the cases. Anicteric hepatitis and thrombocytopenia were observed in 31% and 61% of cases, respectively. One patient died. CONCLUSIONS: High incidences of myocarditis and acute kidney injury were observed, which indicates that the children were treated at a late stage of the disease. Clinicians should be cognizant that myocarditis and acute kidney injury are serious manifestations of pediatric scrub typhus.

Pseudohypoaldosteronism masquerading as congenital adrenal hyperplasia.

A 15-day- old male infant presented with features suggestive of congenital adrenal hyperplasia (CAH). But on detailed investigation, he had normal 17-OH Progesterone and high aldosterone levels. Infant also had right sided hydronephrosis and associated urinary tract infection. Hence, a diagnosis of secondary pseudohypoaldosteronism was made. There was good response to sodium chloride supplementation and he was thriving well on follow up. While evaluating any infant with suspected CAH, one should consider secondary pseudohypoaldosteronism, especially when risk factors like urinary tract obstruction or UTI coexists.

Urate nephropathy associated with impaired kinetic properties of hypoxanthine phosphoribosyl transferase in a 45-day-old infant.

We report a 45-day-old male infant who presented with anuric renal failure and fluid overload due to urate nephropathy consequent upon hyperuricemia with hyperuricosuria. His maternal uncle had undergone renal transplantation for chronic renal failure secondary to uric acid nephrolithiasis. The levels of hypoxanthine phosphoribosyl transferase (HPRT) and adenine phosphoribosyl transferase activity in the baby were found to be quantitatively normal. However, when the HPRT activity was measured at low substrate concentrations [phosphoribosyl pyrophosphate (PRPP) and hypoxanthine] and compared with usual assay conditions, the HPRT activity at lower PRPP was less in the propositus, suggesting altered enzyme kinetics. Apparent K (m(PRPP)) and V (max), but not K (m(hypoxanthine)), were then found to be higher in the propositus than the control range. This is the first case of urate nephropathy secondary to altered enzyme kinetics presenting as early as 45 days. Uric acid nephropathy should be considered in the differential diagnosis of unexplained acute kidney injury in infants. In such cases, quantitative tests for HPRT enzyme activity may not be sufficient and altered enzyme kinetics should also be investigated.

Permanent neurological sequelae following accidental podophyllin ingestion.

Accidental podophyllin poisoning is rare, but it can be associated with high morbidity and mortality. The authors describe severe encephalopathy and cerebral atrophy caused by accidental podophyllin ingestion in a 3-year-old boy. This case illustrates the permanent neurological damage in a developmentally normal child from a preventable cause.

Bilateral ptosis in a child following massive attack by a swarm of wasps.

Neurological manifestations of wasp sting are rare and the etiopathogenesis is not completely understood. We report a 2-year-old girl who developed bilateral ptosis after multiple wasp stings, which responded partially to pyridostigmine. This is the first reported case of wasp venom-induced ptosis in a child. We discuss the possible pathogenetic mechanisms behind this phenomenon.

Cyclosporine A responsive pure red cell aplasia in a child with systemic lupus erythematosus.

PRCA is a rare complication in SLE. Response to various drugs like steroid, Intravenous Immunoglobin (IVIG), recombinant human erythropoietin and plasmapheresis vary in different cases.Cyclosporin A may be effective in cases even unresponsive to other modalities of therapy.