Treatment of genu valgum in children by means of temporary hemiepiphysiodesis using eight-plates: short-term findings

Abstract Background Idiopathic genu valgum is a frequently diagnosed growth disorder in adolescence. Whenever the possibilities of conservative therapy have been exhausted, leg straightening by means of hemiepiphysiodesis has become the standard form of treatment. Because of their flexible screw-plate connection, eight-Plates have been reported in the literature to lead to lower complications regarding implant loosening and fracture compared to other implants. The aim of this retrospective survey was to analyse our own patient population who were treated for genu valgum by means of temporary hemiepiphysiodesis near the knee using eight-Plates to modulate growth. Methods Between July 2007 and July 2015, 198 eight-Plates were implanted near the knee in 132 children suffering from genu valgum to modulate growth. Depending on the deformity analysis, an eight-Plate was implanted on the distal medial femur and/or the proximal medial tibia. By December 2015, they had been removed from 105 patients. The etiology of genu valgum was mainly idiopathic or associated withobesity. Evaluation was carried out clinically and radiologically (whole-leg X-ray in standing) including determination of the joint angles. Results The median follow-up period was about 46 months (12–102 months). The median age at implantation was 12.7 +/−6.76 years. Of the 105 patients, 45.7% (n = 48) were girls. The eight-Plates remained in place for a median period of 13 +/−1.76 months. Irrespective of the location of hemiepiphysiodesis, the intermalleolar distance was corrected to a median of 0 +/−2.1 cm while the anatomical femorotibial angle was corrected by on average 9 +/−2.7 °Mechanical lateral distal femoral angle changed an average 7 +/− 7.72 degrees. Medial proximal tibial angle changed an average 4 +/− 6.02 degrees. Complications necessitating surgery occurred in 2.8% of cases (1 wound infection, 3 corrective osteotomies following overcorrection). Conclusion Temporary hemiepiphysiodesis using eight-Plates is a gentle, simple and effective procedure used to treat genu valgum by modulating growth. Slight overcorrection is desirable due to the rebound phenomenon, especially in young patients with high growth potential and risk groups such as obese children. In adolescents with only low growth potential (older than 14 years), owing to the low correction potential, the indication should be strictly reviewed and the possible failure of therapy should be discussed with the patient. No differences were observed regarding the location of the implanted eight-Plates (femoral or tibial)

The oral microbiome - the relevant reservoir for acute pediatric appendicitis?

Purpose: The oral microbiome has been related to numerous extra oral diseases. Recent studies detected a high abundance of oral bacteria in inflamed appendices in pediatric patients. To elucidate the role of oral bacteria in acute pediatric appendicitis, we studied the oral and appendiceal microbiome of affected children compared to healthy controls. Methods: Between January and June 2015, 21 children undergoing appendectomy for acute appendicitis and 28 healthy controls were prospectively enrolled in the study. All individuals underwent thorough dental examination and laboratory for inflammatory parameters. Samples of inflamed appendices and the gingival sulcus were taken for 16S rDNA sequencing. RT-qPCR of Fusobacterium nucleatum, Peptostreptococcus stomatis, and Eikenella corrodens was performed and their viability was tested under acidic conditions to mimic gastric transfer. Results: In phlegmonous appendices, Bacteroidetes and Porphyromonas were discovered as dominant phylum and genus. In sulcus samples, Firmicutes and Streptococcus were detected predominantly. P. stomatis, E. corrodens, and F. nucleatum were identified in each group. Viable amounts of P. stomatis were increased in sulci of children with acute appendicitis compared to sulci of healthy controls. In inflamed appendices, viable amounts of E. corrodens and F. nucleatum were decreased compared to sulci of children with appendicitis. Postprandial viability could be demonstrated for all tested bacteria. Conclusion: In children with acute appendicitis, we identified several oral bacterial pathogens. Based on postprandial viability of selected species, a viable migration from the oral cavity through the stomach to the appendix seems possible. Thus, the oral cavity could be a relevant reservoir for acute appendicitis

Direct Evidence of Brown Adipocytes in Different Fat Depots in Children

<div><p>Recent studies suggested the persistence of brown adipocytes in adult humans, as opposed to being exclusively present in infancy. In this study, we investigated the presence of brown-like adipocytes in adipose tissue (AT) samples of children and adolescents aged 0 to 18 years and evaluated the association with age, location, and obesity. For this, we analysed AT samples from 131 children and 23 adults by histological, immunohistochemical and expression analyses. We detected brown-like and UCP1 positive adipocytes in 10.3% of 87 lean children (aged 0.3 to 10.7 years) and in one overweight infant, whereas we did not find brown adipocytes in obese children or adults. In our samples, the brown-like adipocytes were interspersed within white AT of perirenal, visceral and also subcutaneous depots. Samples with brown-like adipocytes showed an increased expression of <i>UCP1</i> (>200fold), <i>PRDM16</i> (2.8fold), <i>PGC1α</i> and <i>CIDEA</i> while other brown/beige selective markers, such as <i>PAT2</i>, <i>P2RX5</i>, <i>ZIC1</i>, <i>LHX8</i>, <i>TMEM26</i>, <i>HOXC9</i> and <i>TBX1</i> were not significantly different between UCP1 positive and negative samples. We identified a positive correlation between <i>UCP1</i> and <i>PRDM16</i> within UCP1 positive samples, but not with any other brown/beige marker. In addition, we observed significantly increased <i>PRDM16</i> and <i>PAT2</i> expression in subcutaneous and visceral AT samples with high <i>UCP1</i> expression in adults. Our data indicate that brown-like adipocytes are present well beyond infancy in subcutaneous depots of non-obese children. The presence was not restricted to typical perirenal locations, but they were also interspersed within WAT of visceral and subcutaneous depots.</p></div

Characteristics of the Leipzig Adipose Tissue Childhood Cohort.

<p>Data are given as mean ± SEM (range). For gender, statistical significance was analysed by chi square test. Statistical significance for differences between lean and obese individuals was determined by Students t-test. Significant <i>p</i>-values are indicated in bold. BMI, body-mass index; SDS, standard deviation score; PH, pubertal stage.</p><p>Characteristics of the Leipzig Adipose Tissue Childhood Cohort.</p

Correlation analysis in UCP1^{histological+} samples.

<p>In statistical analyses which were restricted UCP1^{histological+} samples, we observed a negative association between <i>UCP1</i> mRNA and age (A) and a positive association between <i>UCP1</i> mRNA and <i>PRDM16</i> (B). Pearson correlation coefficient R and <i>p</i>-value are shown in each scatterplot. Significant <i>p</i>-values (p<0.05) are indicated in bold. Black circles, subcutaneous depots; white circles, perirenal depots; and black squares, visceral depots.</p

Expression of brown, beige and white adipocyte markers in adipose tissue samples of children and adults.

<p>A: <i>UCP1</i> mRNA expression was significantly increased in UCP1^{histological+} samples compared to lean and obese children as well as adult UCP1^{histological-} samples with the exception of a single outlier from an UCP1^{histological-} subcutaneous sample (indicated as black box). B: <i>PRDM16</i> was also increased in UCP1^{histological+} compared to all other UCP1^{histological-} samples. C, D, E and F: mRNA expression of <i>PAT2</i>, <i>P2RX5</i>, <i>ZIC1</i> and <i>LHX8</i> were not different in UCP1^{histological+} samples, although, one UCP1^{histological+} and one UCP1^{histological-} sample presented exceedingly high <i>PAT2</i> expression values, marked with black squares. G,H and I: mRNA expression of the beige adipocyte markers <i>TMEM26</i> and <i>HOXC9</i> was not different in UCP1^{histological+} samples, although, two UCP1^{histological+} samples (from different donors) presented exceedingly high <i>HOXC9</i> values, marked with black squares. These samples showed only islets of UCP1 positive adipocytes. <i>TBX1</i> mRNA expression was slightly increased in UCP1^{histological-} samples of lean children and obese adults compared to UCP1^{histological+} samples. J and K: The WAT marker <i>LEP</i> was significantly decreased in UCP1^{histological+} samples compared to UCP1^{histological-} samples in contrast to <i>ASC1</i>, another white specific marker. L: <i>ADIPOQ</i>, a general marker for AT was not different between UCP1^{histological+} and UCP1^{histological-} samples. Target gene expression was normalized to the mean of the three housekeeping genes: <i>ACTB</i>, <i>TBP</i> and <i>HPRT1</i>. Statistical significance was assessed by one-way ANOVA and post-hoc Dunnett’s test and was compared to UCP1^{histological+} samples and marked with *<i>P</i><0.05; **<i>P</i>< 0.01; **<i>*P</i><0.001.</p

Correlation of <i>UCP1</i> mRNA expression with anthropometric parameters and expression data in UCP1^{histological+} samples from children (n = 10).

<p>BMI, body-mass index; SDS, standard deviation score; PH, pubertal stage.</p><p>^aPearson correlation analysis was performed for log-transformed <i>UCP1</i> expression levels.</p><p>Correlation of <i>UCP1</i> mRNA expression with anthropometric parameters and expression data in UCP1^{histological+} samples from children (n = 10).</p

Characteristics of adult subjects with low or high <i>UCP1</i> expression levels in AT.

<p>Data are given as mean ± SEM (range). For gender, statistical significance was analysed by chi square test. Statistical significance for differences between groups was determined by Students t-test. Significant <i>p</i>-values are indicated in bold. BMI, body-mass index.</p><p>Characteristics of adult subjects with low or high <i>UCP1</i> expression levels in AT.</p

Immunohistochemical evidence of brown-like adipocytes in adipose tissue samples.

<p>A: Immunohistochemical staining of AT samples showed multilocular adipocytes, which stained positive for UCP1 (black arrows), surrounded by UCP1-negative white unilocular fat cells (white arrows) in subcutaneous (top), perirenal (middle) and visceral (bottom) AT samples of children. B: Two perirenal unilocular samples also exhibited positive UCP1 staining (grey arrows). C: Representative images of UCP1-negative subcutaneous (top, left) and perirenal (top, right) AT samples of lean children and subcutaneous samples of lean adults (bottom). Nuclei were counterstained with Mayer’s hematoxylin. Scale bars represent 50 μm in each panel.</p

Comparison of UCP1^{histological+} and UCP1 ^{histological-}samples.

<p>Data are given as mean ± SEM (range). For gender, statistical significance was analysed by Χ² square test. Statistical significance for differences between groups was determined by Students t-test. Significant <i>p</i>-values are indicated in bold. BMI, body-mass index; SDS, standard deviation score.</p><p>Comparison of UCP1^{histological+} and UCP1 ^{histological-}samples.</p