Scarring In Infants Research Articles

Brain scarring in infants: immunological insights from a neonatal hypoxic-ischemic encephalopathy model

Brain scarring in infants: immunological insights from a neonatal hypoxic-ischemic encephalopathy model

Polymorphisms of the TNF-α, ACE, PAI-1 and MTHFR Genes, and Renal Scarring in Infants with First Febrile Urinary Tract Infection

Polymorphisms of the TNF-α, ACE, PAI-1 and MTHFR Genes, and Renal Scarring in Infants with First Febrile Urinary Tract Infection

Predictors of renal scars in infants with recurrent febrile urinary tract infection: a retrospective, single-center study

Purpose: To determine predictive factors for detecting renal parenchymal damages (RPDs) in infants with recurrent febrile urinary tract infection (fUTI).Methods: From January 2015 to December 2021, 102 infants with recurrent fUTI and who underwent 99mTc-dimercaptosuccinic acid (DMSA) renal scan in our hospital were included in this study. Controls included infants with normal DMSA results performed 3 months apart from the 2nd episode of fUTI. DMSA-positive group included infants with positive DMSA results performed 3 months apart from the 2nd episode of fUTI or at the 3rd episode of fUTI. The recurrence rate, causative bacteria, renal size discrepancy of both kidneys, and laboratory findings including C-reactive protein (CRP) and spot urine sodium-to-potassium ratio (uNa/K) were compared between both groups.Results: Only 3.8% of 79 infants with a 2nd episode of fUTI showed positive DMSA results. fUTI recurred more frequently within 12 months of follow-up in the DMSA-positive group than in the control group (69% vs. 13%, P=0.00). CRP values were significantly higher in the DMSA-positive group than in the control group (7.3 mg/dL vs. 3.7 mg/dL, P=0.00). Spot uNa/K were significantly lower in the DMSA-positive group than in the control group (0.6 vs. 1.1, P=0.00). Conclusions: Congenital renal scar and RPDs on the DMSA scan were more frequently found in infants with recurrent fUTI than those in the control group. High CRP values and low spot uNa/K in acute infections were helpful in predicting the presence of RPD in infants with recurrent fUTI.

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size

BackgroundThis study aimed to evaluate the effect of oral dexamethasone in reducing kidney scars in infants with a first febrile urinary tract infection (UTI).MethodsChildren aged between 2 and 24 months with their first presumed UTI, at high risk for kidney scarring based on procalcitonin levels (≥1 ng/mL), were randomly assigned to receive dexamethasone in addition to routine care or routine care only. Kidney scars were identified by kidney scan at 6 months after initial UTI. Projections of enrollment and follow-up completion showed that the intended sample size could not be reached before funding and time to complete the study ran out. An amendment to the protocol was approved to conduct a Bayesian analysis.ResultsWe randomized 48 children, of whom 42 had a UTI and 18 had outcome kidney scans (instead of 128 planned). Kidney scars were found in 0/7 and 2/11 patients in the treatment and control groups respectively. The probability that dexamethasone could prevent kidney scarring was 99% in the setting of an informative prior probability distribution (which fully incorporated in the final inference the information on treatment effect provided by previous studies) and 98% in the low-informative scenario (which discounted the prior literature information by 50%). The probabilities that dexamethasone could reduce kidney scar formation by up to 20% were 61% and 53% in the informative and low-informative scenario, respectively.ConclusionsDexamethasone is highly likely to reduce kidney scarring, with a more than 50% probability to reduce kidney scars by up to 20%.Trial registration numberEudraCT number: 2013-000388-10; registered in 2013 (prospectively registered)Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

532 Early Debridement and Cultured Allogenic Keratinocyte Dressing Prevent Hypertrophic Scarring in Infants with Deep Dermal Burns

Abstract Introduction Deep dermal burns are frequently treated with excision and skin grafting. Otherwise, wound healing may take up to 4 to 6 weeks, with serious scarring. Especially in pediatric patients, post-burn scarring could result in psychologic trauma and functional disability. We aimed to investigate the efficacy of early debridement and dressing using cultured allogenic keratinocytes in infants with deep dermal burns to prevent hypertrophic scarring. Methods From April 2016 to April 2018, 18 infants were treated for deep dermal burns. Except for 5 infants who underwent skin grafting or excision, 13 infants were included in this study. We performed early debridement in these patients using Hydrosurgery device and serial dressings using cultured allogenic keratinocytes. Results The average operative date was 8.3 days after the accident. The mean healing time was 18.3 days after the accident. The patients did not experience any contraction, but 3 patients had hyperpigmentation, 2 patients had mild hypertrophic scarring, and 1 patient had mixed pigmentation (hyperpigmentation and hypopigmentation). Conclusions Our prophylactic scar therapy, using early debridement with VersajetTM and dressings with Kaloderm®, may be beneficial for infants with dermal burns. This method was able to shorten the healing time, resulting in better scar outcomes. Our follow-up findings revealed that the scars had an aesthetically pleasing appearance and patients were able to perform normal activities without restrictions. Applicability of Research to Practice Burn scars are painful regardless of their seriousness. They restrict the function of the body, are aesthetically unappealing, and may feel unpleasant. Patients with a post-burn scar may have aesthetic, functional, and psychological problems. In particular, infant patients experience difficulties due to scarring as they grow up.

Early Debridement and Cultured Allogenic Keratinocyte Dressing Prevent Hypertrophic Scarring in Infants with Deep Dermal Burns

Early Debridement and Cultured Allogenic Keratinocyte Dressing Prevent Hypertrophic Scarring in Infants with Deep Dermal Burns

Incidence of Abnormal Imaging and Recurrent Pyelonephritis after First Febrile Urinary Tract Infection in Children 2 to 24 Months Old

The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks.

1204 Utility of Serum Procalcitonin to Predict Renal Scars in Infant with Febrile Urinary Tract Infection

Background and AimsThe aim of this study was to evaluate the usefulness of Procalcitonin(PCT) as a marker for renal scars in infants with a first febrile urinary tract infection(UTI).DMSA scintigraphy,...

Risk Factors for Renal Scar Formation in Infants With First Episode of Acute Pyelonephritis: A Prospective Clinical Study

We prospectively determined the risk factors for renal scar formation after the first episode of acute pyelonephritis as confirmed on dimercapto-succinic acid scintigraphy in children younger than 1 year. A total of 213 infants with acute pyelonephritis were enrolled in the study. Infants with urological abnormalities other than vesicoureteral reflux were excluded from analysis. Followup scanning was performed 6 months after acute pyelonephritis and voiding cystourethrography was performed after the acute phase of infection. Possible risk factors were evaluated including gender, peak fever, duration of fever before and after treatment with antibiotics, white blood cell count, C-reactive protein concentration, presence of vesicoureteral reflux and reflux grade. Six months after acute pyelonephritis 37 of 213 (17.4%) infants and 41 of 248 (16.5%) renal units with acute photon defects on initial dimercapto-succinic acid scintigraphy had renal scars. The rates of scar formation were significantly higher in infants with vesicoureteral reflux than in those without (39.4% vs 7.5%, p <0.001, OR 9.433) and in renal units with vesicoureteral reflux than in those without (39.4% vs 8.2%, p <0.001, OR 7.237). Renal scar formation was related to reflux grade (none-8.2%, grade I-20%, grade II-22.7%, grade III-40%, grade IV-70%, grade V-55.6%, p <0.001) but not to any other clinical or laboratory variables. The presence of vesicoureteral reflux was the only independent risk factor for renal scar formation after acute pyelonephritis in infants. The prevalence of renal scarring was significantly correlated with reflux grade. Voiding cystourethrography is necessary in infants after the first acute pyelonephritis episode is confirmed on dimercapto-succinic acid renal scintigraphy.

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

The Role of Procalcitonin for Acute Pyelonephritis and Subsequent Renal Scarring in Infants and Young Children

We assessed the usefulness of procalcitonin as a biological marker in diagnosing acute pyelonephritis and for predicting subsequent renal scarring in young children with a first febrile urinary tract infection. Children 2 years old or younger with a first febrile urinary tract infection were prospectively studied. Renal parenchymal involvement was assessed by (99m)Tc-dimercaptosuccinic acid scan within 5 days of admission and after 6 months. Serum samples from all patients were tested for procalcitonin, C-reactive protein and white blood cell count measurements. The 112 enrolled patients (age range 24 days to 24 months old) were divided into acute pyelonephritis (76) and lower urinary tract infection (36) groups according to the results of (99m)Tc-dimercaptosuccinic acid scans. Median values of procalcitonin, C-reactive protein and white blood cell count at hospitalization were significantly higher in patients with acute pyelonephritis than in those with lower urinary tract infection. The area under receiver operating characteristic curves showed that procalcitonin was superior to C-reactive protein and white blood cell count as a marker for diagnosing acute pyelonephritis. Initial and post-antibiotic treatment procalcitonin values were significantly higher in children with renal scarring than in those without scarring (p <0.001). Procalcitonin values at hospitalization and after treatment were independent predictors of later renal scarring on logistic regression analysis. Our results indicate the superior diagnostic accuracy of procalcitonin for predicting acute pyelonephritis in children 2 years old or younger. Higher initial and posttreatment procalcitonin values are independent risk factors for later renal scarring.

Polymorphisms of the TNF-α and ACE Genes, and Renal Scarring in Infants With Urinary Tract Infection

Susceptibility to renal scarring is increasingly investigated through polymorphisms of genes regulating inflammation and fibrosis. TNF-alpha and ACE gene polymorphisms have been studied in chronic renal conditions but their role in urinary tract infection and vesicoureteral reflux associated renal scarring is unclear. We investigated the relationship between TNF-alpha A/G and ACE I/D polymorphisms, and renal scarring after urinary tract infection in infants. ACE I/D and TNF-alpha -308 A/G polymorphisms were investigated with restriction fragment length polymorphism analysis in 39 boys and 25 girls with a first urinary tract infection before age 2 years and in 77 controls. Genotype and allele frequencies were compared among children with urinary tract infection with and without renal scarring, and controls. ACE I/D genotype frequencies were similar among infants with urinary tract infection with and without renal scarring, and controls. However, all 6 children with severe renal scarring and impaired renal function bore a D allele, 5 of which were DD homozygotes. D allele was more common in these severely affected children than in their peers with urinary tract infection and mild or no renal scarring (OR 9.92, 95% CI 1.24-79, p = 0.012), and controls (OR 8.03, 95% CI 1.01-64, p = 0.029). No differences were observed in TNF-alpha A/G genotype frequencies among the 3 groups. Presence of vesicoureteral reflux was not related to phenotypes or allele frequencies. Our findings suggest that D allele polymorphism of the ACE gene is associated with urinary tract infection related severe renal scarring in young children.

Procalcitonin as a predictor of renal scarring in infants and young children

The aim of this study was to evaluate the usefulness of procalcitonin (PCT) as a marker of renal scars in infants and young children with a first episode of acute pyelonephritis. Children aged 7 days to 36 months admitted for first febrile urinary tract infection (UTI) to a pediatric emergency department were prospectively enrolled. The PCT concentration was determined at admission. Acute (99m)Tc-dimercaptosuccinic acid (DMSA) scintigraphy was performed within 7 days of admission and repeated 12 months later when abnormal findings were obtained on the first scan. Of the 72 children enrolled in the study, 52 showed signs of acute pyelonephritis (APN) on the first DMSA scan. A follow-up scintigraphy at the 12-month follow-up performed on 41 patients revealed that 14 (34%) patients had developed renal scars; these patients also presented significantly higher PCT values than those without permanent renal lesions [2.3 (interquartile range 1-11.6) vs. 0.5 (0.2-1.4) ng/mL; p = 0.007]. A comparison of the PCT concentration in patients with febrile UTI without renal involvement, with APN without scar development and with APN with subsequent renal scarring revealed a significant increasing trend (p = 0.006, Kruskal-Wallis test). The area under the ROC curve for scar prediction was 0.74 (95% confidence interval 0.61-0.85), with an optimum statistical cut-off value of 1 ng/mL (sensitivity 78.6%; specificity 63.8%). Based on these results, we suggest that serum PCT concentration at admission is a useful predictive tool of renal scarring in infants and young children with acute pyelonephritis.

Incidence of Post-Pyelonephritic Renal Scarring: A Meta-Analysis of the Dimercapto-Succinic Acid Literature

We investigated ethnic differences in the risk of post-pyelonephritic renal scarring in infants and children for possible genetic determinants. We searched all peer reviewed articles published from 1980 through 2006 in the PubMed(R), MEDLINE(R) (Ovid), Cochrane Central Register of Controlled Trials and EMBASE(R) databases for the keywords, "renal scarring and pyelonephritis," "renal fibrosis" and "kidney scarring." References were included only when they specified acute pyelonephritis defined by a fever, positive urine culture and areas of photopenia in the renal cortex on 99mtechnetium dimercapto-succinic acid renal scans, repeat dimercapto-succinic acid scans obtained at least 3 months after acute pyelonephritis to assess for renal cortical scar formation and absence of recurrent urinary tract infection during followup. When possible data were analyzed according to patients and renal units. Among 23 references the overall rates of renal scarring in terms of patients and renal units were 41.6% and 37.0%, respectively. In terms of patients the incidence of renal scarring following acute pyelonephritis varied by region, from 26.5% (Australia) to 49.0% (Asia). In terms of renal units the incidence of acquired renal cortical scarring varied by region, from 16.7% (Middle East) to 58.4% (Asia). When combined by vesicoureteral reflux status children and renal units with refluxing ureters exhibited an increased risk of renal scarring (odds ratios 2.8 and 3.7, respectively). Although scarring was different across some regions, only scarring in Asian studies comparing patients displayed a statistically significant difference. A regional effect explained the heterogeneity observed in the overall estimate for patients and partly for renal units. The greatest risk of renal scarring may be imparted by the presence of vesicoureteral reflux.

Longitudinal Analyses of Renal Lesions Due to Acute Pyelonephritis in Children and Their Impact on Renal Growth

Acute pyelonephritis is a common condition in children, and can lead to renal scarring. The aim of this study was to analyze the progression of renal scarring with time and its impact on renal growth. A total of 50 children who had renal scarring on dimercapto-succinic acid scan 6 months after acute pyelonephritis underwent a repeat scan 3 years later. Lesion changes were evaluated by 3 blinded observers, and were classified as no change, partial resolution or complete disappearance. Renal size at time of acute pyelonephritis and after 3 years was obtained by ultrasound, and renal growth was assessed comparing z-score for age between the 2 measures. Robust linear regression was used to identify determinants of renal growth. At 6 months after acute pyelonephritis 88 scars were observed in 100 renal units. No change was observed in 27%, partial resolution in 63% and complete disappearance in 9% of lesions. Overall, 72% of lesions improved. Increased number of scars was associated with high grade vesicoureteral reflux (p = 0.02). Multivariate analysis showed that the number of scars was the most important parameter leading to decreased renal growth (CI -1.05 to -0.35, p <0.001), and with 3 or more scars this finding was highly significant on univariate analysis (-1.59, CI -2.10 to -1.09, p <0.0001). Even 6 months after acute pyelonephritis 72% of dimercapto-succinic acid defects improved, demonstrating that some of the lesions may be not definitive. The number of scars was significantly associated with loss of renal growth at 3 years.

Abnormal Renal Scans and Decreased Early Resolution of Low Grade Vesicoureteral Reflux

Limited studies suggest a relationship between scarring on renal scan and failure to resolve vesicoureteral reflux. We evaluated the impact of abnormal renal scans on early vesicoureteral reflux resolution. The medical records and renal scans were reviewed of children diagnosed with primary reflux between 1988 and 2004. We defined an abnormal renal scan as renal scarring or relative renal function 40% or less. Reflux resolution was noted 1 and 2 years after diagnosis. Renal scan data were available on 161 children with vesicoureteral reflux, including 127 girls and 34 boys. Relative renal function was 15% or less in 7 children, 16% to 35% in 14, 36% to 40% in 18 and greater than 40% in 122. Of the 161 patients 79 (43%) had an abnormal renal scan, including 37% with grades 1 to 3 reflux. The rate of 2-year reflux resolution in the abnormal and normal renal scan groups was 13% vs 53%. Of children with grades II and III reflux those with an abnormal renal scan were less likely to have reflux resolution compared to those with normal renal scans (23% vs 55% and 4% vs 41, respectively, p <0.05). The same relationship was present at 1 year for grades 2 and 3 (18% vs 49% and 4% vs 30, respectively, p <0.05). Abnormal renal scans are an important independent predictor of early failure to resolve vesicoureteral reflux. An abnormal renal scan should be considered when counseling families about the likelihood of early reflux resolution. Performing a renal scan may be indicated in select patients.

Endoscopically Assisted Sural Nerve Harvest in Infants

A technique of endoscopic sural nerve harvest was devised to minimize the donor site scarring in infants requiring peripheral nerve grafting procedures. The harvests were performed under tourniquet control using three 2-cm incisions for access at the lateral malleolus, midcalf, and popliteal fossa. Endoscopic visualization and blunt dissection of the nerve was achieved with a 4-mm-diameter, 18-cm-long telescope with a 0-degree angle lens, stabilized in an Emory retractor and attached to a video camera. The medial sural nerve was divided in the popliteal fossa proximally under direct vision. The lateral sural nerve was identified and harvested when present. This technique has been in use since 1994 and has been undertaken in more than 200 patients. The most common indication for surgery was obstetrical brachial plexus palsy. No nerve graft injury was noted upon examination under the operating microscope. Postoperative pain, swelling, and ecchymosis were minimal. Most patients have a detectable area of sensory loss at long-term follow-up but are unaware of this finding. Donor site scarring has been aesthetically satisfactory.

Antibiotic Prophylaxis for the Prevention of Recurrent Urinary Tract Infection in Children With Low Grade Vesicoureteral Reflux: Results From a Prospective Randomized Study

Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux. Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test. A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042). These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux.

Does Early Treatment of Urinary Tract Infection Prevent Renal Damage?

Therapeutic delay has been suggested as the most important factor that is likely to have an effect on the development of scarring after acute pyelonephritis. However, this opinion has not been supported by prospective studies, so we tested it. In a prospective clinical study, we evaluated whether the time interval between the onset of the renal infection and the start of therapy correlates with the development of acute inflammatory changes and the subsequent development of renal scars, documented by dimercaptosuccinic acid scintigraphy. A total of 278 infants (153 male and 125 female) aged 0.5 to 12.0 months with their first urinary tract infection were enrolled in the study. The median time between the onset of infection and the institution of therapy was 2 days (range: 1-8 days). Renal inflammatory changes were documented in 57% of the infants. Renal defects were recorded in 41% of the patients treated within the first 24 hours since the onset of fever versus 75% of those treated on day 4 and onward. Renal scarring was developed in 51% of the infants with an abnormal scan in the acute phase of infection. The frequency of scarring in infants treated early and in those whose treatment was delayed did not differ, suggesting that once acute pyelonephritis has occurred, ultimate renal scarring is independent of the timing of therapy. Acute inflammatory changes and subsequent scarring were more frequent in the presence of vesicoureteral reflux, especially that which is high grade. However, the difference was not significant, which suggests that renal damage may be independent of the presence of reflux. Early and appropriate treatment of urinary tract infection, especially during the first 24 hours after the onset of symptoms, diminishes the likelihood of renal involvement during the acute phase of the infection but does not prevent scar formation.

TUMOR NECROSIS FACTOR-α GENE POLYMORPHISM IN REFLUX NEPHROPATHY

Interstitial scarring contributes to the progression of renal failure in reflux nephropathy. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the disease susceptibility and pathogenesis of several inflammatory diseases promoting interstitial infiltration of inflammatory cells. We evaluate the frequency of TNF-alpha gene polymorphism in patients with reflux nephropathy. Renal scarring was evaluated with technetium dimercapto-succinic acid renal scan. Genotyping was performed on 104 patients with reflux nephropathy and 30 controls for the TNF-alpha gene polymorphisms using polymerase chain reaction and restriction digest. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A). The allele frequencies of TNF1 and TNF2 were 18.8% and 81.2% in patients with reflux nephropathy and 76.7% and 23.3% in controls, respectively. The genotype distribution of TNF-alpha-AA was significantly higher (66.4% vs 10%, p <0.05), while the TNF-alpha-GG was lower (13.4% vs 60%, p <0.05) in patients with reflux nephropathy compared to controls. This study demonstrates for the first time the association of the cytokine TNF-alpha gene polymorphism in patients with reflux nephropathy. Our data suggest that patients with vesicoureteral reflux and TNF-alpha AA genotype may have increased susceptibility to reflux nephropathy.