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.

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.

Comparison of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in treatment of adolescent varicocele: A 15-year review.

INTRODUCTION/OBJECTIVE: Varicocele is a common condition seen in adolescence and associated with adult subfertility. Numerous types of intervention have been described with differences in success and complication rates. This study aims to review and compare the surgical outcomes of laparoscopic Palomo surgery and scrotal antegrade sclerotherapy at our center. STUDY DESIGN: A retrospective analysis was done of all patients younger than 18 years old with idiopathic varicocele treated operatively between February 2001 and December 2016. Demographics such as age at operation, side, varicocele grade, operative date, and types of operation were collected. Primary outcomes were clinical recurrence, defined as any grading noted on follow-up within 1 year post-op and post-operative hydrocele. Secondary outcomes were operative time, length of stay, and other surgical complications. Mann-Whitney U test, independent t test and chi-square tests were used for analysis. All p-values were two-sided and considered statistically significant at p ≤ 0.05. RESULTS: A total of 119 patients fit the criteria, of whom 117 patients were included in data analysis (Table). Sixty-two patients had laparoscopic Palomo surgery (LPS) and 55 had scrotal antegrade sclerotherapy (SAS). Clinical recurrence (grade 2-3) within 1 year was similar between the two groups, with four out of 48 patients in the SAS group and six out of 62 patients in the LPS group (8.4% in SAS vs. 9.7% in LPS, p = 1.00). Of the 11 patients who had recurrence in the SAS group, seven had grade 1 recurrence (14.5%), two (4.2%) had grade 2 recurrence, and two (4.2%) had grade 3 recurrence. For the LPS group, 17 out of 62 patients had clinical recurrence within 1 year, of whom 11 (17.7%) had grade 1 recurrence, one (1.6%) had grade 2, and five (8.1%) had grade 3 recurrence. Post-operative hydrocele was significantly higher in the LPS group; there was none in the SAS group but 11 patients in the LPS group (0% in SAS vs. 17.7%, p = 0.002). Three patients had clinically significant hydrocele requiring Jaboulays' procedure. Complications other than hydrocele were noted in three patients in the SAS group and one patient in the LPS group (5.5% in SAS vs. 1.6% in LPS, p = 0.158). None required operative intervention. No conversion to open procedure was seen in the LPS group and there were no perioperative complications. Mean operative time was 62.9 min in the SAS group and 60.7 min in the LPS group (p = 0.624). Mean length of stay was 17.5 h in the SAS group and 31.7 h in the LPS group (p < 0.001). CONCLUSION: Both SAS and LPS are safe procedures for treatment of adolescent varicocele with similar clinical recurrence rate within 1 year. SAS has a significantly lower rate of post-operative hydrocele.

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.

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.

Determination of absolute expression profiles using multiplexed miRNA analysis.

Accurate measurement of miRNA expression is critical to understanding their role in gene expression as well as their application as disease biomarkers. Correct identification of changes in miRNA expression rests on reliable normalization to account for biological and technological variance between samples. Ligo-miR is a multiplex assay designed to rapidly measure absolute miRNA copy numbers, thus reducing dependence on biological controls. It uses a simple 2-step ligation process to generate length coded products that can be quantified using a variety of DNA sizing methods. We demonstrate Ligo-miR's ability to quantify miRNA expression down to 20 copies per cell sensitivity, accurately discriminate between closely related miRNA, and reliably measure differential changes as small as 1.2-fold. Then, benchmarking studies were performed to show the high correlation between Ligo-miR, microarray, and TaqMan qRT-PCR. Finally, Ligo-miR was used to determine copy number profiles in a number of breast, esophageal, and pancreatic cell lines and to demonstrate the utility of copy number analysis for providing layered insight into expression profile changes.

Venous Malformation and Localized Intravascular Coagulopathy in Children.

Aim Localized intravascular coagulopathy (LIC) has been described in adults with venous malformation (VM) but rarely reported in children. This study aims to determine the prevalence of LIC in children with VM and associated risk factors. Methods Patients younger than 18 years with VM from 2010 to 2014 were reviewed. Diagnosis was confirmed by Doppler ultrasound and/or magnetic resonance imaging. Demographics data and VM characteristics including volume, site, extension, painful symptoms, and palpable phleboliths were studied. Plasma D-dimer level of greater than 500 ng/mL was considered as abnormal. Results Total 24 children were included, of whom 8 were boys. Median age of presentation was 9 months (range: 0-12 years). Head-and-neck VM occurred in 17 (70.8%) patients and 3 (12.5%) had multifocal lesions. Seven (29.2%) patients had VM volume greater than 10 mL. Five (20.8%) patients had painful symptoms. Palpable phleboliths were found in two patients. Plasma D-dimer was raised in eight cases (33.3%). One patient with Klippel-Trenaunay syndrome (KTS) had D-dimer level of 5,000 ng/mL. Raised D-dimer was found in 23.5% of small VM (volume < 10 mL) and 57.1% of large VM (p = 0.167). D-dimer was significantly raised in multifocal VM (p = 0.028) and showed increasing trend in lesions with palpable phleboliths (p = 0.101). All patients had sclerotherapy performed with indications (cosmesis 41.7%, enlarging lesion 29.2%, pain 20.8%, bleeding 8.3%). Perioperatively, bolus intravenous fluid and mannitol were given to selected patients. All patients had VM volume reduction after sclerotherapy. There were no major thromboembolic complications. Conclusion LIC with raised D-dimer level occurred in one-third of pediatric VM. It was more common in large, multifocal VM and in those with palpable phleboliths or KTS.

A Simple Thermoplastic Substrate Containing Hierarchical Silica Lamellae for High-Molecular-Weight DNA Extraction.

An inexpensive, magnetic thermoplastic nanomaterial is developed utilizing a hierarchical layering of micro- and nanoscale silica lamellae to create a high-surface-area and low-shear substrate capable of capturing vast amounts of ultrahigh-molecular-weight DNA. Extraction is performed via a simple 45 min process and is capable of achieving binding capacities up to 1 000 000 times greater than silica microparticles.

Efficient synthesis of stably adenylated DNA and RNA adapters for microRNA capture using T4 RNA ligase 1.

MicroRNA profiling methods have become increasingly important due to the rapid rise of microRNA in both basic and translational sciences. A critical step in many microRNA profiling assays is adapter ligation using pre-adenylated adapters. While pre-adenylated adapters can be chemically or enzymatically prepared, enzymatic adenylation is preferred due to its ease and high yield. However, previously reported enzymatic methods either require tedious purification steps or use thermostable ligases that can generate side products during the subsequent ligation step. We have developed a highly efficient, template- and purification-free, adapter adenylation method using T4 RNA ligase 1. This method is capable of adenylating large amounts of adapter at ~100% efficiency and can efficiently adenylate both DNA and RNA bases. We find that the adenylation reaction speed can differ between DNA and RNA and between terminal nucleotides, leading to bias if reactions are not allowed to run to completion. We further find that the addition of high PEG levels can effectively suppress these differences.

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.

Management of the low-flow head and neck vascular malformations in children: the sclerotherapy protocol.

AIM: Image-guided sclerotherapy is becoming the preferred treatment for low-flow vascular malformations in head and neck region. The authors review the management protocol for this condition and evaluate its clinical outcomes. METHODS: Children with low-flow vascular malformations in head and neck region undergoing sclerotherapy from 2010 to 2013 were reviewed. All patients were assessed by pediatric surgeons and interventional radiologists in the multidisciplinary vascular anomalies clinic. Ultrasonography and intravenous contrast enhanced magnetic resonance imaging were performed preoperatively. Under general anesthesia with endotracheal intubation, sclerotherapy were performed with ultrasonographic and fluoroscopic guidance. Sodium tetradecryl sulfate (STS) foam or ethanolamine was used for venous malformation and doxycycline for lymphatic malformations as primary sclerosants, whereas 98% ethanol was reserved as an adjuvant sclerosant in selected cases of repeated procedures. Perioperative dexamethasone 0.2 mg/kg thrice daily was administered to decrease postsclerotherapy swelling and single dose intravenous mannitol 0.5 g/kg was given to minimize thromboembolic complications. Postoperatively, patients were admitted to intensive care unit for mechanical ventilation under deep sedation for airway protection. RESULTS: Overall 13 children (8 male and 5 female) with a mean age of 25 months (range, 2 mo-11 y) underwent a total of 25 sessions of image-guided staged sclerotherapy. There were five venous and eight lymphatic malformations. Location wise there were eight cervical, one lingual, one parotid, one lip, one facial, and one palatal lesions. Six patients had obstructive airway symptoms. Five patients required staged sclerotherapies from two to six sessions. There were no airway and thromboembolic complications. One patient had bleeding while another had recurrent swelling following sclerotherapy for lymphatic malformations and they were treated by aspiration. Significant size reductions of more than 50% volume were achieved in all patients. All patients with obstructive symptoms showed improvement. CONCLUSION: Sclerotherapy is a safe and effective treatment for head and neck vascular malformations in children. Routine perioperative protocol is essential to reduce airway and thromboembolic complications. Size reduction and functional improvement occurred in all patients undergoing sclerotherapy.

Pancreatic kaposiform hemangioendothelioma presenting with duodenal obstruction and kasabach-merritt phenomenon: a neonate cured by whipple operation.

Aim Kaposiform hemangiondothelioma (KHE) is a rare vascular tumor, commonly associated with Kasaback-Merritt phenomenon characterized by thrombocytopenia and consumptive coagulopathy. We report a case of pancreatic KHE presenting with neonatal duodenal obstruction and Kasaback-Merritt phenomenon. Case Report A full term male baby presented with bile stained vomiting on Day 3 of life. Contrast study and computed tomography scan showed duodenal obstruction by a 5 cm extrinsic hypervascular mass. Platelet count was 23 x 109/L. Laparotomy confirmed a vascular tumor arising from the pancreatic head compressing on the duodenum. Whipple operation was performed. Results Intestinal obstruction and thrombocytopenia resolved after surgery. There was no post-operative complications. Histology confirmed KHE. The boy was tolerating hydrolyzed milk formula and was thriving at 5 months follow up. Conclusion We reported a case of pancreatic KHE presented with neonatal intestinal obstruction and Kasaback-Merritt phenomenon. High index of suspicion is necessary for diagnosis. To our knowledge, this is the youngest patient who underwent Whipple operation.

Retroperitoneal pelvic packing for haemodynamically unstable pelvic fractures in children and adolescents: a level-one trauma-centre experience.

PURPOSE: This study aims to review the outcomes of haemodynamically unstable paediatric patients with pelvic fractures undergoing protocol intervention of retroperitoneal pelvic packing (RPP) with external fixation and angiography. METHODS: From 2004 to 2011, consecutive patients younger than 19 years treated in our centre for haemodynamically unstable pelvic fractures were retrospectively reviewed. From 2008, protocol intervention triad of external fixation, RPP, and angiography with embolization was implemented. RESULTS: Before 2008, only 2 boys with fall injuries received intervention. One received initial angiography showing extravasation near iliac bifurcation. Laparotomy proceeded without embolization for multiple visceral injuries, but he succumbed postoperatively. The other had persistent bleeding after external fixation but became stabilized after embolization. After 2008 protocol implementation, 5 youngsters received the triad of interventions for unstable pelvic fractures. Mean age was 15.4 yrs. The mean injury severity score was 42 (18-66) with 62.5% mean probability of survival (6.8-98.8%). The mean operating time for RPP was 23 mins (20-35 mins). One boy died of rapid exanguination intraoperatively. The other 4 youngsters recovered for rehabilitation. CONCLUSION: Fall from heights is a major cause for severe pelvic injuries in our locality. RPP is a simple effective procedure to include in protocol intervention for pelvic fractures. This case series suggests it helps improve haemostasis and survival in unstable young patients, although larger cohorts will be necessary to validate this.

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.

Mapping DNA quantity into electrophoretic mobility through quantum dot nanotethers for high-resolution genetic and epigenetic analysis.

Newly discovered nanoparticle properties have driven the development of novel applications and uses. We report a new observation where the electrophoretic mobility of a quantum dot/DNA nanoassembly can be precisely modulated by the degree of surface DNA conjugation. By using streptavidin-coated quantum dots (QDs) as nanotethers to gather biotin-labeled DNA into electrophoretic nanoassemblies, the QD surface charge is modulated and transformed into electrophoretic mobility shifts using standard agarose gel electrophoresis. Typical fluorescent assays quantify based on relative intensity. However, this phenomenon uses a novel approach that accurately maps DNA quantity into shifts in relative band position. This property was applied in a QD-enabled nanoassay called quantum dot electrophoretic mobility shift assay (QEMSA) that enables accurate quantification of DNA targets down to 1.1-fold (9%) changes in quantity, beyond what is achievable in qPCR. In addition to these experimental findings, an analytical model is presented to explain this behavior. Finally, QEMSA was applied to both genetic and epigenetic analysis of cancer. First, it was used to analyze copy number variation (CNV) of the RSF1/HBXAP gene, where conventional approaches for CNV analysis based on comparative genomic hybridization (CGH), microarrays, and qPCR are unable to reliably differentiate less than 2-fold changes in copy number. Then, QEMSA was used for DNA methylation analysis of the p16/CDK2A tumor suppressor gene, where its ability to detect subtle changes in methylation was shown to be superior to that of qPCR.

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.

A surface topography assisted droplet manipulation platform for biomarker detection and pathogen identification.

This paper reports a droplet microfluidic, sample-to-answer platform for the detection of disease biomarkers and infectious pathogens using crude biosamples. The platform exploited the dual functionality of silica superparamagnetic particles (SSP) for solid phase extraction of DNA and magnetic actuation. This enabled the integration of sample preparation and genetic analysis within discrete droplets, including the steps of cell lysis, DNA binding, washing, elution, amplification and detection. The microfluidic device was self contained, with all reagents stored in droplets, thereby eliminating the need for fluidic coupling to external reagent reservoirs. The device incorporated unique surface topographic features to assist droplet manipulation. Pairs of micro-elevations were created to form slits that facilitated efficient splitting of SSP from droplets. In addition, a compact sample handling stage, which integrated the magnet manipulator, the droplet microfluidic device and a Peltier thermal cycler, was built for convenient droplet manipulation and real-time detection. The feasibility of the platform was demonstrated by analysing ovarian cancer biomarker Rsf-1 and detecting Escherichia coli with real time polymerase chain reaction and real time helicase dependent amplification.

PCR-free, microfluidic single molecule analysis of circulating nucleic acids in lung cancer patient serum.

Circulating nucleic acid (CNA) has been the focus of much recent research, studied both as a diagnostic marker and as a marker for enrichment of diseased DNA. Among these markers, circulating DNA fragment size has shown promise for discerning the source of CNA molecules in cancer and prenatal diagnostics due to differences in average size between cancer vs. healthy or fetal vs. maternal DNA. We describe a 1-step assay for analyzing circulating DNA size and quantity directly in human serum that replaces complicated nested qPCR analysis. Microfluidic cylindrical illumination confocal spectroscopy and fluorescence burst size analysis were used to individually count and size fluorescently-labeled CNA molecules as they were driven through a microfluidic constriction. First, single molecule sizing was performed on λ Hind III digest DNA to obtain a size calibration curve. A linear relation between DNA length and fluorescent burst size was seen from 564 bp-23.1 kbp. Then, the single molecule assay was used to analyze an in vitro model of DNA fragmentation. Finally, DNA sizing analysis was successfully 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. Furthermore, it eliminated the need for DNA isolation or enzymatic amplification. This demonstrates that microfluidic single molecule spectroscopy can be a rapid, facile, and inexpensive alternative to the established PCR-based methods.