Early post-operative interleukin-6 and tumor necrosis factor-α levels after single-port laparoscopic varicocelectomy in children

PURPOSE: Laparoendoscopic single-site surgery has recently been described in children and regarded as an improved technology leading to less pain and better cosmetic outcome. Compared to the traditional three-port method, it is not known if the single-port method is less invasive. The aim of this study was thus to investigate the post-operative acute inflammatory response in order to evaluate surgical stress in the two surgical approaches in children. METHODS: A prospective, single blinded, case-control study was carried out. Thirteen male patients who presented with unilateral varicocele were divided into two groups. Six children underwent single-port laparoscopic procedure, while the other seven children underwent three-port laparoscopic procedure. Pre-operative and post-operative blood samples were taken for the measurement of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) using ELISA. Demographics including the operation time, and complications were recorded. Data between the two groups were analyzed using unpaired t-test and a p value of <0.05 was taken as statistically significant. RESULTS: The mean age of patients was 14.5 years (range 12-19 years). There was no significant difference between the two groups in terms of operative time, nor there was any complication recorded. The change in serum TNF-alpha and IL-6 concentrations pre- and post-operatively between the single-port group and three-port group was not statistically significant. Overall, patients in the two groups showed excellent satisfaction in terms of post-operative cosmesis. CONCLUSION: Single-port laparoscopic varicocelectomy is safe, effective and produces excellent cosmesis with minimal surgical stress.published_or_final_versionSpringer Open Choice, 21 Feb 201

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring:population based cohort study

textabstractObjective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design Population based cohort study. Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously

Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure

Gua Sha is a traditional Chinese folk therapy that employs skin scraping to cause subcutaneous microvascular blood extravasation and bruises. The protocol for bioluminescent optical imaging of HO-1-luciferase transgenic mice reported in this manuscript provides a rapid in vivo assay of the upregulation of the heme oxygenase-1 (HO-1) gene expression in response to the Gua Sha procedure. HO-1 has long been known to provide cytoprotection against oxidative stress. The upregulation of HO-1, assessed by the bioluminescence output, is thought to represent an antioxidative response to circulating hemoglobin products released by Gua Sha. Gua Sha was administered by repeated strokes of a smooth spoon edge over lubricated skin on the back or other targeted body part of the transgenic mouse until petechiae (splinter hemorrhages) or ecchymosis (bruises) indicative of extravasation of blood from subcutaneous capillaries was observed. After Gua Sha, bioluminescence imaging sessions were carried out daily for several days to follow the dynamics of HO-1 expression in multiple internal organs

Validation of graft and standard liver size predictions in right liver living donor liver transplantation

Purpose: To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. Methods: The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Results: Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, (R 2 = 0.476) (p = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively (R 2 = 0.781) (p = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. Conclusion: SLV and graft weight estimations were accurate using the formula and conversion factor. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Host Genetics Predict Clinical Deterioration in HCV-Related Cirrhosis

Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31–6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0–1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96–3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13–7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents:A Self-Controlled Case Series Study

BACKGROUND: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning. METHODS: Patients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods). RESULTS: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males. CONCLUSIONS: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00824-x

Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury