The evolution of synaptic and cognitive capacity: Insights from the nervous system transcriptome of Aplysia.

The gastropod mollusk Aplysia is an important model for cellular and molecular neurobiological studies, particularly for investigations of molecular mechanisms of learning and memory. We developed an optimized assembly pipeline to generate an improved Aplysia nervous system transcriptome. This improved transcriptome enabled us to explore the evolution of cognitive capacity at the molecular level. Were there evolutionary expansions of neuronal genes between this relatively simple gastropod Aplysia (20,000 neurons) and Octopus (500 million neurons), the invertebrate with the most elaborate neuronal circuitry and greatest behavioral complexity? Are the tremendous advances in cognitive power in vertebrates explained by expansion of the synaptic proteome that resulted from multiple rounds of whole genome duplication in this clade? Overall, the complement of genes linked to neuronal function is similar between Octopus and Aplysia. As expected, a number of synaptic scaffold proteins have more isoforms in humans than in Aplysia or Octopus. However, several scaffold families present in mollusks and other protostomes are absent in vertebrates, including the Fifes, Lev10s, SOLs, and a NETO family. Thus, whereas vertebrates have more scaffold isoforms from select families, invertebrates have additional scaffold protein families not found in vertebrates. This analysis provides insights into the evolution of the synaptic proteome. Both synaptic proteins and synaptic plasticity evolved gradually, yet the last deuterostome-protostome common ancestor already possessed an elaborate suite of genes associated with synaptic function, and critical for synaptic plasticity.

Are all patients with short segment Hirschsprung's disease equal? A retrospective multicenter study.

BACKGROUND/PURPOSE: Short segment Hirschsprung's disease (HSCR) carries a better prognosis than long segment disease, but the definition of short is controversial. The objective of this study is to determine anatomically the extent of disease involvement that would be associated with a better functional outcome. METHODS: This is a retrospective multicenter (n = 3) study with patients (≥ 3 years) who had transanal pullthrough operation done for aganglionosis limited to the recto-sigmoid colon were reviewed. The extent of disease involvement and bowel resection was retrieved by reviewing the operative records as well as histopathological reports of the resected specimens. Clinical assessment was performed according to the criteria of a seven-itemed bowel function score (BFS) (maximum score = 20). Manometric assessment was performed with anorectal manometry. RESULTS: The study period started from 2003 to 45 patients were studied with median age at assessment = 52.0 months and operation = 3.0 months. The disease involvement was categorized into upper sigmoid-descending colon (DC) (n = 8), sigmoid colon (SC) (n = 12), upper rectum (UR) (n = 14) and lower rectum (LR) (n = 11) according to the level of normal biopsy result. There was no significant difference in the age of assessment between the four groups. The median BFSs in the DC, SC, UR and LR were 13, 15, 17 and 17, respectively (p = 0.01). Nine patients from the DC and SC groups reported soiling for more than twice per week. Sub-group analysis comparing patients with and without the entire sigmoid colon resected revealed worse functional outcomes in terms of the incidence of soiling (40.7 vs 22.2%, p = 0.05) and the BFS (14 vs 18, p = 0.04) in the former group. Anorectal manometry did not reveal any significant difference between the four groups, but a higher proportion of patients in the UR and LR groups appeared to have a normal sphincter resting pressure (DC vs SC vs UR vs LR = 62.5 vs 75.0 vs 85.7 vs 80.0%, p = 0.10). CONCLUSION: Patients with short segment HSCR are not equal at all. HSCR patients with aganglionosis limited to the rectum without the need of removing the entire sigmoid colon have a better bowel control and overall functional score. Less bowel loss and colonic dissection maybe the underlying reasons. Although future studies with a larger sample size and a longer follow-up period are required to validate the results of this study, it has provided a new insight to the current understanding of short segment disease in HSCR.

Single Molecule Hydrodynamic Separation Allows Sensitive and Quantitative Analysis of DNA Conformation and Binding Interactions in Free Solution.

Limited tools exist that are capable of monitoring nucleic acid conformations, fluctuations, and distributions in free solution environments. Single molecule free solution hydrodynamic separation enables the unique ability to quantitatively analyze nucleic acid biophysics in free solution. Single molecule fluorescent burst data and separation chromatograms can give layered insight into global DNA conformation, binding interactions, and molecular distributions. First, we show that global conformation of individual DNA molecules can be directly visualized by examining single molecule fluorescent burst shapes and that DNA exists in a dynamic equilibrium of fluctuating conformations as it is driven by Poiseuille flow through micron-sized channels. We then show that this dynamic equilibrium of DNA conformations is reflected as shifts in hydrodynamic mobility that can be perturbed using salt and ionic strength to affect packing density. Next, we demonstrate that these shifts in hydrodynamic mobility can be used to investigate hybridization thermodynamics and binding interactions. We distinguish and classify multiple interactions within a single sample, and demonstrate quantification amidst large concentration differences for the detection of rare species. Finally, we demonstrate that these differences can resolve perfect complement, 2 bp mismatched, and 3 bp mismatched sequences. Such a system can be used to garner diverse information about DNA conformation and structure, and potentially be extended to other molecules and mixed-species interactions, such as between nucleic acids and proteins or synthetic polymers.

From observation to aetiology: a case report of a twin fetus-in-fetu and a revisit of the known rarity.

A baby girl presented with an antenatal diagnosis of a retroperitoneal tumour. Postnatal imaging suggested that this mass contained two fetiform structures with spine and long bone formation. This teratomatous mass was completely excised at 3 weeks of age. Histology was consistent with twin fetuses-in-fetu, revealing two fetiform masses each with an umbilical cord connecting to a common placenta-like mass. Despite a difference in the weight of the twin fetuses-in-fetu, the level of organogenesis was identical and corresponded to fetuses of 10 weeks of gestation. Each mass had four limbs, intact skin, rib cage, intestines, anus, ambiguous genitalia, primitive brain tissue and a spine with ganglion cells in the cord. Although considered a mature teratoma in the current World Health Organization classification, the theory of formation from multiple pregnancies has been commonly implied in more recent literature. The true aetiology of this rare condition remains unclear.

Direct interrogation of DNA content distribution in nanoparticles by a novel microfluidics-based single-particle analysis.

Nonviral gene delivery holds great promise not just as a safer alternative to viral vectors in traditional gene therapy applications, but also for regenerative medicine, induction of pluripotency in somatic cells, and RNA interference for gene silencing. Although it continues to be an active area of research, there remain many challenges to the rational design of vectors. Among these, the inability to characterize the composition of nanoparticles and its distribution has made it difficult to probe the mechanism of gene transfection process, since differences in the nanoparticle-mediated transfection exist even when the same vector is used. There is a lack of sensitive methods that allow for full characterization of DNA content in single nanoparticles and its distribution among particles in the same preparation. Here we report a novel spectroscopic approach that is capable of interrogating nanoparticles on a particle-by-particle basis. Using PEI/DNA and PEI-g-PEG/DNA nanoparticles as examples, we have shown that the distribution of DNA content among these nanoparticles was relatively narrow, with the average numbers of DNA of 4.8 and 6.7 per particle, respectively, in PEI/DNA and PEI-g-PEG/DNA nanoparticles. This analysis enables a more accurate description of DNA content in polycation/DNA nanoparticles. It paves the way toward comparative assessments of various types of gene carriers and provides insights into bridging the efficiency gap between viral and nonviral vehicles.

Identification of the major sex pheromone component of the scale insect, Aulacaspis murrayae Takahashi.

(R)-Solanone was identified as a female-specific compound from aerations of virgin females of the scale insect, Aulacaspis murrayae Takahashi. The stereochemistry of the insect-produced solanone was confirmed to be (R) by comparison with synthesized racemic and chiral standards on a chiral stationary phase GC column. In bioassays, males were strongly attracted to a synthesized sample of (R)-solanone, demonstrating that this compound is a sex pheromone component for this species.

Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review.

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility.

Hong Kong Chinese parents' attitudes towards circumcision.

OBJECTIVE: To investigate Hong Kong Chinese parents' knowledge and attitudes towards phimosis and circumcision. DESIGN: Questionnaire survey. SETTING: Four primary schools in Hong Kong. PARTICIPANTS: Anonymous questionnaires were sent to Chinese parents of boys, aged 6 to 12 years old, studying in primary school Grades 1 to 6. Their social backgrounds, attitudes and beliefs towards phimosis and circumcision were enquired into. RESULTS: The parents of 1479 pupils answered the questionnaire, giving a response rate of 95.8%. In all, 10.7% of schoolboys had undergone circumcision, and 11.8% of the fathers were circumcised. Regarding non-circumcised boys, 28.9% of their parents believed that their sons had phimosis and 15.6% believed they would require circumcision later. Among these parents, 57.9% would consider circumcision for their boys in public hospitals, 96.9% thought that public institutions should provide such service, and 82.6% thought that doctors' opinions were most important when deciding about circumcision. Most parents believed that circumcision could prevent balanitis (82.8%) and improve hygiene (81.8%). Significantly more parents from Mainland China and of lower social class believed that circumcision could improve cosmesis, growth of the penis, sexual potency and fertility, and prevent sexually transmitted diseases and penile cancer. CONCLUSION: Circumcision is not widely practised in Hong Kong. However, it can be a potential burden on surgical services in public hospitals. There are misconceptions concerning phimosis and circumcision, especially in parents from Mainland China and from lower socio-economic classes. Doctors' opinions are the most important factor guiding parental decisions on circumcision. Thus, family physicians' advice and education are important to avoid unnecessary circumcisions.

Serial transverse enteroplasty for short bowel syndrome: Hong Kong experience.

OBJECTIVE: To report our experience with the first series of serial transverse enteroplasty operations (a novel bowel-lengthening procedure for patients with short bowel syndrome). DESIGN. Case series. SETTING: A tertiary paediatric surgery referral centre in Hong Kong. PATIENTS: Four patients with short bowel syndrome aged 11 months to 14 years underwent serial transverse enteroplasty between November 2007 and June 2010. RESULTS: A total of six such serial procedures were performed; two patients had repeated operations. Median pre-serial transverse enteroplasty small bowel length was 17.5 cm. The median increase in small bowel length was 90%. One patient experienced transient postoperative intestinal obstruction that resolved after conservative management. The median postoperative follow-up period was 31 months. The median enteral nutrition tolerance increased from 24% to 47%. The median weight-for-age z score increased by 0.55, and the median weight-for-height z score increased by 0.98. One patient had successfully weaned off parenteral nutrition. CONCLUSION: Serial transverse enteroplasty is a feasible and safe treatment for short bowel syndrome patients, which helps to improve enteral nutrition and promote growth. Repeated serial transverse enteroplasty can be performed in patients with ultra-short bowel lengths. Follow-up is necessary to assess the long-term outcomes.

Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) degrades transcripts with premature stop codons. Given the prevalence of nonsense single nucleotide polymorphisms (SNPs) in the general population, it is urgent to catalog the effects of clinically approved drugs on NMD activity: any interference could alter the expression of nonsense SNPs, inadvertently inducing adverse effects. This risk is higher for patients with disease-causing nonsense mutations or an illness linked to dysregulated nonsense transcripts. On the other hand, hundreds of disorders are affected by cellular NMD efficiency and may benefit from NMD-modulatory drugs. Here, we profiled individual FDA-approved drugs for their impact on cellular NMD efficiency using a sensitive method that directly probes multiple endogenous NMD targets for a robust readout of NMD modulation. We found most FDA-approved drugs cause unremarkable effects on NMD, while many elicit clear transcriptional responses. Besides several potential mild NMD modulators, the anticancer drug homoharringtonine (HHT or omacetaxine mepesuccinate) consistently upregulates various endogenous NMD substrates in a dose-dependent manner in multiple cell types. We further showed translation inhibition mediates HHT's NMD effect. In summary, many FDA drugs induce transcriptional changes, and a few impact global NMD, and direct measurement of endogenous NMD substrate expression is robust to monitor cellular NMD.

Single-molecule analysis enables free solution hydrodynamic separation using yoctomole levels of DNA.

Single-molecule free solution hydrodynamic separation (SML-FSHS) cohesively integrates cylindrical illumination confocal spectroscopy with free solution hydrodynamic separation. This technique enables single-molecule analysis of size separated DNA with 100% mass detection efficiency, high sizing resolution and wide dynamic range, surpassing the performance of single molecule capillary electrophoresis. Furthermore, SML-FSHS required only a bare fused silica microcapillary and simple pressure control rather than complex high voltage power supplies, sieving matrices, and wall coatings. The wide dynamic range and high sizing resolution of SML-FSHS was demonstrated by separating both large DNA (23 vs 27 kbp) and small DNA (100 vs 200 bp) under identical conditions. Separations were successfully performed with near zero sample consumption using as little as 5 pL of sample and 240 yoctomoles (∼150 molecules) of DNA. Quantitative accuracy was predominantly limited by molecular shot noise. Furthermore, the ability of this method to analyze of single molecule nanosensors was investigated. SML-FSHS was used to examine the thermodynamic equilibrium between stochastically open molecular beacon and target-bound molecular beacon in the detection of E. coli 16s rRNA targets.

Minimally invasive chest drain insertion in children.

A minimally invasive technique of chest drain insertion using the Mini Step bladeless trocar is described. Thirty-one chest drain insertions were performed with this technique between January 2007 and December 2009. It is a safe, efficient, fast, and easily acquired means of chest drain insertion in children, which has a high success rate and minimal morbidity. Overwhelmingly positive responses were obtained from doctors of all levels who used this technique, which is highly recommended for chest drain insertion in conscious children.

Otitis media with effusion and hearing loss in Chinese children with cleft lip and palate.

OBJECTIVE: To determine the incidence of otitis media with effusion and the associated hearing loss, the rate of ventilation tube insertion, and complications of ventilation tube insertion in Chinese cleft palate patients. DESIGN: Retrospective review in a tertiary care hospital in Hong Kong. PATIENTS: A total of 104 consecutive patients with cleft lip and/or cleft palate who were born between January 1996 and January 2006. RESULTS: The incidence of otitis media with effusion in Chinese cleft palate patients for the first 2 years after birth was 76.1%. Of these patients, 16.9% had otitis media with effusion associated with a moderate hearing loss (>40 decibels hearing level [dBHL]). Approximately half (53.2%) of our patients had ventilation tube insertion. Complications including retraction, tympanosclerosis, and perforation of the tympanic membrane were found in 15.7% of all ears with otitis media with effusion and ventilation tube insertion. CONCLUSIONS: The high incidence of otitis media with effusion in cleft palate infants found in this study is consistent with that reported in the Western literature. A small but significant proportion of otitis media with effusion was associated with moderate hearing loss that truly required surgical treatment. Cleft palate children are much more likely to develop otitis media with effusion than normal children, and they develop the condition at an earlier age. A protocol for the treatment of otitis media with effusion in cleft palate patients and further prospective studies are warranted.

Sex chromosome transformation and the origin of a male-specific X chromosome in the creeping vole.

The mammalian sex chromosome system (XX female/XY male) is ancient and highly conserved. The sex chromosome karyotype of the creeping vole (Microtus oregoni) represents a long-standing anomaly, with an X chromosome that is unpaired in females (X0) and exclusively maternally transmitted. We produced a highly contiguous male genome assembly, together with short-read genomes and transcriptomes for both sexes. We show that M. oregoni has lost an independently segregating Y chromosome and that the male-specific sex chromosome is a second X chromosome that is largely homologous to the maternally transmitted X. Both maternally inherited and male-specific sex chromosomes carry fragments of the ancestral Y chromosome. Consequences of this recently transformed sex chromosome system include Y-like degeneration and gene amplification on the male-specific X, expression of ancestral Y-linked genes in females, and X inactivation of the male-specific chromosome in male somatic cells. The genome of M. oregoni elucidates the processes that shape the gene content and dosage of mammalian sex chromosomes and exemplifies a rare case of plasticity in an ancient sex chromosome system.

Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy.

Circulating nucleic acid (CNA) has been the focus of recent research as a noninvasive source of biomarker candidates. Among these markers, DNA fragment size has shown promise for discerning the source of CNA molecules in cancer and prenatal diagnostics. We have developed a one-step assay for analyzing circulating DNA size and quantity directly in human serum. Microfluidic cylindrical illumination confocal spectroscopy and fluorescence burst size analysis are used to individually count and size fluorescently-labeled CNA molecules as they are driven through a microfluidic constriction. First, single molecule sizing was performed on lambda Hind III digest DNA to obtain a size calibration curve. A linear relation between DNA length and burst size was seen from 564 bp to 27.5 kbp. Subsequently, the single molecule assay parameters were optimized. Finally, DNA sizing analysis was performed on serum samples from both early and late stage lung cancer patients. This assay was performed directly in patient serum using only a single reagent, a simple DNA intercalating dye, and without the need for DNA isolation or enzymatic amplification steps. This demonstrates that microfluidic single molecule spectroscopy can be a rapid, facile, and inexpensive alternative to the established PCR-based methods that have been used near exclusively for CNA analysis.

Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes.

De novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a single PromethION nanopore sequencer and our toolkit, we assembled 11 highly contiguous human genomes de novo in 9 d. We achieved roughly 63× coverage, 42-kb read N50 values and 6.5× coverage in reads >100 kb using three flow cells per sample. Shasta produced a complete haploid human genome assembly in under 6 h on a single commercial compute node. MarginPolish and HELEN polished haploid assemblies to more than 99.9% identity (Phred quality score QV = 30) with nanopore reads alone. Addition of proximity-ligation sequencing enabled near chromosome-level scaffolds for all 11 genomes. We compare our assembly performance to existing methods for diploid, haploid and trio-binned human samples and report superior accuracy and speed.

Cylindrical illumination confocal spectroscopy: rectifying the limitations of confocal single molecule spectroscopy through one-dimensional beam shaping.

Cylindrical illumination confocal spectroscopy (CICS) is a new implementation of single molecule detection that can be generically incorporated into any microfluidic system and allows highly quantitative and accurate analysis of single fluorescent molecules. Through theoretical modeling of confocal optics and Monte Carlo simulations, one-dimensional beam shaping is used to create a highly uniform sheet-like observation volume that enables the detection of digital fluorescence bursts while retaining single fluorophore sensitivity. First, we theoretically show that when used to detect single molecules in a microchannel, CICS can be optimized to obtain near 100% mass detection efficiency, <10% relative SD in burst heights, and a high signal/noise ratio. As a result, CICS is far less sensitive to thresholding artifacts than traditional single molecule detection and significantly more accurate at determining both burst rate and burst parameters. CICS is then experimentally implemented, optically characterized, and integrated into separate two microfluidic devices for the analysis of fluorescently stained plasmid DNA and single Cy5 labeled oligonucleotides. CICS rectifies the limitations of traditional confocal spectroscopy-based single molecule detection without the significant operational complications of competing technologies.

Tunable blinking kinetics of cy5 for precise DNA quantification and single-nucleotide difference detection.

Fluorescence correlation spectroscopy (FCS) can resolve the intrinsic fast-blinking kinetics (FBKs) of fluorescent molecules that occur on the order of microseconds. These FBKs can be heavily influenced by the microenvironments in which the fluorescent molecules are contained. In this work, FCS is used to monitor the dynamics of fluorescence emission from Cy5 labeled on DNA probes. We found that the FBKs of Cy5 can be tuned by having more or less unpaired guanines (upG) and thymines (upT) around the Cy5 dye. The observed FBKs of Cy5 are found to predominantly originate from the isomerization and back-isomerization processes of Cy5, and Cy5-nucleobase interactions are shown to slow down these processes. These findings lead to a more precise quantification of DNA hybridization using FCS analysis, in which the FBKs play a major role rather than the diffusion kinetics. We further show that the alterations of the FBKs of Cy5 on probe hybridization can be used to differentiate DNA targets with single-nucleotide differences. This discrimination relies on the design of a probe-target-probe DNA three-way-junction, whose basepairing configuration can be altered as a consequence of a single-nucleotide substitution on the target. Reconfiguration of the three-way-junction alters the Cy5-upG or Cy5-upT interactions, therefore resulting in a measurable change in Cy5 FBKs. Detection of single-nucleotide variations within a sequence selected from the Kras gene is carried out to validate the concept of this new method.

Surgical Outcome Analysis of Pneumovesicoscopic Ureteral Reimplantation and Endoscopic Dextranomer/Hyaluronic Acid Injection for Primary Vesicoureteral Reflux in Children: A Multicenter 12-Year Review.

OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition associated with childhood urinary tract infection (UTI), which may lead to chronic renal failure and hypertension. Different antireflux approaches were advocated with differences in morbidity and success. The aim of this study is to review and analyze the surgical outcomes of pneumovesicoscopic ureteral reimplantation and endoscopic injection of dextranomer/hyaluronic acid (Dx/HA) in three tertiary centers. MATERIALS AND METHODS: The medical records of 215 patients (159 boys and 56 girls) for a total of 323 ureters underwent surgical interventions for primary VUR from February 2002 to August 2014 were reviewed. Data on baseline demographics, preoperative symptoms, radiological imaging studies, and postoperative outcomes were analyzed. VUR resolution was defined as when no VUR was detected by micturating cystourethrogram at 3 months or later after the intervention. Independent t-test, Mann-Whitney U test, Fisher's Exact test, and Chi-Square test were used for different parameters. All results with P value ≤.05 were regarded as statistically significant. RESULTS: The mean age at operation was 3.33 and 4.63 for reimplantation and Dx/HA injection respectively. A total of 234 ureters underwent Dx/HA injection and 92 ureters underwent pneumovesicoscopic ureteral reimplantation with mean preoperative VUR grading of 3.1 and 4.2 respectively (P = .0001). The overall VUR downgrading and resolution rates were both significantly higher in reimplantation than Dx/HA injection (97.8% versus 78.6% P = .0001 and 84.3% versus 65% P = .0011). Further subgroup analyses across the different VUR gradings showed higher downgrading and resolution rates in reimplantation group than Dx/HA injection for grade 4 (100% versus 81% P = .0147 and 82.4% versus 63% P = .0411) and grade 5 VUR (97.3% versus 50% P = .0022 and 81.6% versus 40% P = .0256). Dx/HA injection was associated with shorter operation time (41.5 minutes versus 147.5 minutes, P < .001), less postoperative analgesic usage (P = .049), and shorter hospital stay (1.06 days versus 4.44 days P < .0001). No major complications were identified in both groups. The mean follow-up time was significantly longer in reimplantation group than Dx/HA group (57.25 months versus 37.85 months, P = .002). There was no significant difference in the rate of subsequent UTI development during follow-up (P = .8). CONCLUSIONS: Both Dx/HA injection and pneumovesicoscopic ureteral reimplantation are safe and effective treatments for VUR. Reimplantation is associated with significantly higher VUR downgrading and resolution rates than Dx/HA injection especially in the higher grade VUR while Dx/HA injection has significantly shorter operation time, lower postoperative analgesic usage, and shorter hospital stay. Dx/HA injection can be considered as the first line surgical treatment especially for lower grade VUR. Pneumovesicoscopic ureteral reimplantation can be used for higher grade reflux or those who failed Dx/HA treatments.

D-dimer level correlation with treatment response in children with venous malformations.

AIM: Localized intravascular coagulopathy is present in children with venous malformations (VMs) as evidenced by elevated D-dimer levels. Few studies have looked into the changes in D-dimer after sclerotherapy and its correlation with treatment outcome and complications. Our study aims to investigate changes in D-dimer in children with VMs undergoing alcohol sclerotherapy. METHODS: A prospective cohort study from 2014 to 2016, which included children (<18years) with VM undergoing alcohol sclerotherapy, was completed. Demographics and lesion characteristics were recorded. Perioperative D-dimer levels were collected 2weeks prior to treatment (baseline) and on postoperative days 1, 2, 5, and 14, respectively. A raised postoperative D-dimer was defined as a peak level of at least 50% increase of baseline D-dimer. Children were followed up with documentation of lesional size at 6months and long-term recurrence beyond 6months of treatment. RESULTS: Eighteen children were identified (10 females, 8 males) with a median follow up of 21months. Overall, 15 patients (83%) had a satisfactory outcome. Baseline D-dimer levels were high in 8 patients (44%). Postoperative D-dimer level was raised in 12 patients irrespective of their baseline levels, with 92% peaking on postoperative day one (n=11). In the elevated D-dimer group, 11 patients had a satisfactory outcome, and 10 patients did not have long-term recurrence. We did not encounter any complications in our cohort. CONCLUSION: Changes in perioperative D-dimer levels may predict early treatment response and long-term recurrence after alcohol sclerotherapy. With a standardized protocol, alcohol sclerotherapy for venous malformation is safe with minimal complications. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: IV.