Major surgical conditions of childhood and their lifelong implications: comprehensive review.

BACKGROUND: In recent decades, the survival of children with congenital anomalies and paediatric cancer has improved dramatically such that there has been a steady shift towards understanding their lifelong health outcomes. Paediatric surgeons will actively manage such conditions in childhood and adolescence, however, adult surgeons must later care for these 'grown-ups' in adulthood. This article aims to highlight some of those rare disorders encountered by paediatric surgeons requiring long-term follow-up, their management in childhood and their survivorship impact, in order that the adult specialist may be better equipped with skills and knowledge to manage these patients into adulthood. METHODS: A comprehensive literature review was performed to identify relevant publications. Research studies, review articles and guidelines were sought, focusing on the paediatric management and long-term outcomes of surgical conditions of childhood. The article has been written for adult surgeon readership. RESULTS: This article describes the aforementioned conditions, their management in childhood and their lifelong implications, including: oesophageal atresia, tracheo-oesophageal fistula, malrotation, short bowel syndrome, duodenal atresia, gastroschisis, exomphalos, choledochal malformations, biliary atresia, Hirschsprung disease, anorectal malformations, congenital diaphragmatic hernia, congenital lung lesions and paediatric cancer. CONCLUSION: The increasing survivorship of children affected by surgical conditions will translate into a growing population of adults with lifelong conditions and specialist healthcare needs. The importance of transition from childhood to adulthood is becoming realized. It is hoped that this timely review will enthuse the readership to offer care for such vulnerable patients, and to collaborate with paediatric surgeons in providing successful and seamless transitional care.

Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Oesophageal lengthening by traction in oesophageal atresia: The UK experience.

AIMS: Preliminary reports suggest a promising role for oesophageal lengthening by traction (OLBT) in long gap oesophageal atresia (LGOA). Nevertheless, these encouraging results originate from specialist centres, and real-world experience is unquantified. We report the first multicentre, nationwide study of OLBT. METHODS: Cumulative experience of OLBT was recorded through a questionnaire sent to all UK paediatric surgery centres. OLBT was defined as "any attempt to increase oesophageal length using tension sutures". Contributors submitted all cases of attempted OLBT, regardless of outcome. Demographics, surgical detail, and outcomes were analysed with summary statistics. RESULTS: The response rate was 23/26 centres. Eleven centres reported using OLBT in 22 patients (2003-2020) with 117 LGOA treated by other means. One patient died from complications of cardiac surgery and was excluded. OLBT enabled oesophageal anastomosis in 16 (76%), of which 2 died of complications of surgery, and another died of unrelated disease. Of the survivors, 7 required oesophageal dilatation 2-14 times. Oesophageal anastomosis was not achieved in 5 (24%) patients. All had pouch leak or disruption pre- or peri-operatively and underwent cervical oesophagostomy with subsequent gastric pull-up. One patient required dilatation of the oesophagogastric anastomosis. CONCLUSION: OLBT is being carried out in the UK in a limited number of centres in a minority of patients. These data suggest OLBT enables oesophageal anastomosis in 76% of infants with LGOA. Oesophageal pouch leak or disruption was common to all instances of failure to anastomose. Our findings will inform discussions between surgeons and families of babies born with LGOA.

Is Roux-en-Y Feeding Jejunostomy a Safe and Effective Operation in Children? A Systematic Review Exploring Outcomes.

OBJECTIVES: Roux-en-Y jejunostomy (REYJ) may establish feeding in children with foregut dysmotility or severe gastro-esophageal reflux disease (GERD). Nevertheless, concerns have been raised about safety and efficacy. We, therefore, evaluated outcomes of REYJ by systematic review to determine if this was a satisfactory option for achieving enteral autonomy in children with complex nutritional needs. METHODS: A PRISMA-adherent systematic review was conducted of studies reporting children undergoing feeding REYJ. Two authors performed processes independently; the senior author resolved disagreements. Embase, CINAHL and Medline were searched (inception-01/21). Additional databases, references, and 'grey' literature were searched. Methodological Index for Non-randomized Studies (MINORS) and a bespoke system assessed methodological quality. RESULTS: Of 362 articles, 10 met eligibility criteria (9 retrospective series; 1 conference proceeding). Unpublished data were also attained. Interobserver agreement for MINORS (kappa = 0.47) and bespoke scoring (kappa = 0.58) were moderate. After consensus, median MINORS score was 37.5% (IQR 6.3%) and bespoke 50% (IQR 20.8%), indicating poor methodological quality. One hundred sixty-four patients were reported (age range: 2 months to 19 years). Time to full feeds and length of stay were inadequately reported but most achieved enteral autonomy. No studies reported patient/caregiver-questionnaires. Seventy-six complications were documented (Clavien-Dindo grading was infeasible). Morbidity included peristomal leakage (N = 26), internal hernia/volvulus (N = 8), and SSI (N = 7). Thirty-eight patients died (2 procedure-attributable) during follow-up (range: 1 month to 15 years). CONCLUSIONS: Up to 50% patients experience complications after REYJ (often minor) with 23% patients dying during follow-up, often comorbidity-attributable. REYJ can achieve enteral autonomy although parents/caregivers of children should be counselled accordingly.

Retrospective analysis of testicular outcomes following laparoscopic two-stage Fowler Stephens orchidopexy.

AIM OF THE STUDY: Few large series report outcomes for laparoscopic two-stage Fowler Stephens orchidopexy (LFSO). The aims were to evaluate testicular outcomes and to identify factors predictive of successful outcome. METHOD: A retrospective case series of children undergoing laparoscopic surgery for impalpable testes between May 1996 and March 2018 was reviewed. Data were collected from case and operative records. The primary outcomes of interest were testicular atrophy or re-ascent. Regression analysis was conducted to identify factors predictive of successful outcome. Data was expressed as median (IQR). RESULTS: Of 279 patients (300 testes) undergoing laparoscopy for impalpable testis, 114 patients (128 testes) underwent LFSO. Eighty-five patients (96 testes) had adequate follow-up available (53 left; 43 right). Age at first stage was 19 (IQR 13-36) months. Fifteen children had relevant co-morbidities. Time between procedures was 7 (IQR 6-8) months. Longest follow-up available was 12.5 months (IQR 6.8-19.8). Atrophy occurred in 8 testes (8.3%), and ascent occurred in 6 (6.3%). No factors were significantly predictive of success, although a trend towards atrophy was seen amongst testes undergoing gubernacular division compared with a gubernaculum-sparing technique (p = 0.06; OR 3; 95% CI 0.97-9.3). CONCLUSION: A successful outcome was seen amongst 82 of 96 testes (85%) undergoing LFSO, similar to previous reports. No factors were identified that significantly predicted outcome. Number of adverse outcomes was limited (hence possibility of type II error), and therefore preservation of the gubernaculum may reduce risk of testicular atrophy. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Spuriously raised serum amylase in a five-year-old girl: a note of caution in paediatric blood sampling.

INTRODUCTION: Capillary (finger prick) blood sampling is commonplace in paediatric practice but this method is prone to produce spurious laboratory results. CASE PRESENTATION: A five-year-old girl presented with abdominal pain, epigastric tenderness, tachycardia and reduced oxygen saturation. A venous blood sample haemolysed, and serum amylase on a finger prick sample was reported as 2831 units/L. The working diagnosis was acute pancreatitis and respiratory tract infection. A repeat amylase 9 h later was within the normal range. The patient was known to bite her fingers and the possibility of salivary contamination was considered. Serum isoenzyme analysis confirmed presence of high salivary amylase levels with no pancreatic amylase detected. A viral respiratory tract infection and buried gastrostomy bumper were eventually thought to account for the patient's presentation. CONCLUSION: Increased awareness of the potential for salivary contamination of serum amylase in finger prick samples may prevent misdiagnoses of pancreatitis.

Quantification of urinary sodium concentrations in term infants.

BACKGROUND: Infants with gastrointestinal conditions and poor weight gain are administered sodium supplementation based on urinary sodium concentrations. However, the reference range of urinary electrolytes is unknown. The aim of this study was to ascertain the normal values of urinary electrolytes in healthy, term infants. Secondary aims were to establish the relationship between urinary electrolytes with weight velocity and feeding practices. METHODS: Healthy, term (≥37 weeks' gestation) infants were recruited. Parental questionnaires were completed before discharge and at six weeks. Electrolytes were quantified from a urine sample at six weeks. t-Tests and Mann-Whitney U tests were conducted for parametric and non-parametric electrolytes, respectively. RESULTS: A total of 200 infants were recruited before discharge. Twenty-nine follow-up questionnaires and urine samples were returned (nine female; mean gestational age 39 + 6 weeks [SD 9.9 days]; mean birthweight 3350 g [SD 483 g]; 17 breastfed, nine formula and three mixed; mean change in Z score for weight -0.914 [SD 0.814]). Majority (25/29) of infants had urinary sodium <20 mmo/L. Change in Z score for weight was similar between infants with sodium <20 mmol/L and >20 mmol/L ( P = 0.78). All exclusively breastfed infants had sodium <20 mmol/L, however, not statistically dissimilar to formula-fed infants ( P = 0.27). CONCLUSION: Most term infants in this study had urinary sodium values <20 mmol/L with no identified relationship to weight velocity. Lower concentrations of sodium could be not quantified reliably because of the limitations of the analytical method that were used. More evidence is required to identify candidates for sodium supplementation.

Major complications of jejunal feeding in children.

AIM OF THE STUDY: The aim of the study was to identify major gastrointestinal complications associated with direct jejunal feeding. We hypothesized that jejunal feeding may cause life-threatening surgical complications in a minority of patients. METHODS: All patients undergoing jejunal feeding between 1/2008 and 1/2018 at a pediatric surgical unit were identified retrospectively. Data sought from records included demographics, comorbidities, indications, feeding strategies, adverse events, and follow-up. Major surgical complications were defined by Clavien-Dindo grade ≥ IIIb and involving the GI tract (excluding changes of jejunal tube). MAIN RESULTS: 197 patients were identified (110 female). Median age (IQR) at initiation of jejunal feeding months was 5.6 (6-164) months. 122 were neurologically impaired. The most frequent indications were: GERD/gastroparesis (n = 114), prophylaxis/treatment of Superior Mesenteric Artery (SMA) syndrome (N.B. our center is a national spinal deformity unit) (n = 47), congenital anomalies of aerodigestive anatomy (n = 17), and malignancy (n = 7). 125 patients were managed with nasojejunal feeding alone: gastrojejunal tube (n = 51) and via Roux-en-Y jejunostomy (n = 21). There were 14 significant gastrointestinal complications (n = 11 grade > IIIb) identified among 12 patients, of whom 8 required bowel resections, and 2 died as a result: nonmechanical bowel ischemia (n = 7), intussusception (n = 4), and volvulus (n = 3). CONCLUSION: This series highlights the major complications of jejunal feeding, including a significant yet underreported risk of gut compromise. Patients undergoing jejunal feeding had a 6.1% risk of developing major surgical complications (of note, 3.6% developed bowel ischemia of unknown etiology). Susceptible children were comorbid, fragile, and neurologically impaired. These findings should influence parental discussions and informed consent before embarking upon jejunal feeding. LEVEL OF EVIDENCE: Level IV prognosis study.

An audit of bilious vomiting in term neonates referred for pediatric surgical assessment: can we reduce unnecessary transfers?

BACKGROUND: Between 20% and 50% neonates with bilious vomiting are diagnosed with surgical pathology. Distinguishing neonates requiring surgery remains challenging. Our aim was to conduct an audit of term neonates with bilious vomiting referred for assessment to identify characteristics of this cohort and management. Secondary aims were to identify factors predictive of surgical pathology. METHODS: Infants <28 days referred for bilious vomiting from 2011 to 2015 were identified through cross-referencing multiple patient databases. Data obtained included clinical features, laboratory, radiological investigations and management. The sensitivity and specificity of tests were calculated and regression analyses were conducted to identify predictors of surgical pathology. RESULTS: 351 eligible neonates were referred [46% female; mean gestation 39 + 6 weeks (SD 9.2 days); mean birthweight 3469 g (SD 558 g)]. Laboratory results were available for 68.7% patients, 88.9% underwent X-ray and 96.6% contrast studies. 11.7% had a surgical diagnosis [malrotation 4.6% (1.7% with volvulus)]. No single test available in peripheral centers could exclude a surgical diagnosis. In regression analyses, age > 72 h, presence of abdominal distension, raised CRP and abnormal X-ray were statistically significant predictors of surgical pathology, while only the former two were predictive of time-critical surgical pathology. CONCLUSION: 11.7% neonates had surgical pathology, fewer than in previous studies. Only contrast fluoroscopy could exclude surgical pathology and therefore prevent transfer. A more sensitive, widely available test would be required to reduce unnecessary neonatal transfers. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level III.

George Macaulay: A short biography and his place in the history of congenital diaphragmatic hernia.

George Macaulay (1716-1766) was a Scot admired for his work as an obstetric physician, philanthropist, author, and feminist, but whom history has largely forgotten. In a time rampant with misogyny, Macaulay empathized with women, discouraged sexism within institutions, and contributed to the training of midwives. He spent much of his career working at the British Lying-in Hospital in London. Perhaps most importantly, he worked tirelessly for this hospital, contributed to various medical innovations, and reported several medical cases throughout his career, including that of congenital diaphragmatic hernia, almost a century before the anatomist whose eponymous name it bears. The purpose of this article is to reappraise the life, achievements, and specifically, the role of George Macaulay in our understanding of CDH.

A systematic review of the quality of conduct and reporting of systematic reviews and meta-analyses in paediatric surgery.

OBJECTIVE: Our objective was to evaluate quality of conduct and reporting of published systematic reviews and meta-analyses in paediatric surgery. We also aimed to identify characteristics predictive of review quality. BACKGROUND: Systematic reviews summarise evidence by combining sources, but are potentially prone to bias. To counter this, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was published to aid in reporting. Similarly, the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) measurement tool was designed to appraise methodology. The paediatric surgical literature has seen an increasing number of reviews over the past decade, but quality has not been evaluated. METHODS: Adhering to PRISMA guidelines, we performed a systematic review with a priori design to identify systematic reviews and meta-analyses of interventions in paediatric surgery. From 01/2010 to 06/2016, we searched: MEDLINE, EMBASE, Cochrane, Centre for Reviews and Dissemination, Web of Science, Google Scholar, reference lists and journals. Two reviewers independently selected studies and extracted data. We assessed conduct and reporting using AMSTAR and PRISMA. Scores were calculated as the sum of reported items. We also extracted author, journal and article characteristics, and used them in exploratory analysis to determine which variables predict quality. RESULTS: 112 articles fulfilled eligibility criteria (53 systematic reviews; 59 meta-analyses). Overall, 68% AMSTAR and 56.8% PRISMA items were reported adequately. Poorest scores were identified with regards a priori design, inclusion of structured summaries, including the grey literature, citing excluded articles and evaluating bias. 13 reviews were pre-registered and 6 in PRISMA-endorsing journals. The following predicted quality in univariate analysis:, word count, Cochrane review, journal h-index, impact factor, journal endorses PRISMA, PRISMA adherence suggested in author guidance, article mentions PRISMA, review includes comparison of interventions and review registration. The latter three variables were significant in multivariate regression. CONCLUSIONS: There are gaps in the conduct and reporting of systematic reviews in paediatric surgery. More endorsement by journals of the PRISMA guideline may improve review quality, and the dissemination of reliable evidence to paediatric clinicians.

Mechanistic insights from resolving ligand-dependent kinetics of conformational changes at ATP-gated P2X1R ion channels.

Structural studies of P2X receptors show a novel U shaped ATP orientation following binding. We used voltage clamp fluorometry (VCF) and molecular dynamics (MD) simulations to investigate agonist action. For VCF the P2X1 receptor (P2X1R) K190C mutant (adjacent to the agonist binding pocket) was labelled with the fluorophore MTS-TAMRA and changes in fluorescence on agonist treatment provided a real time measure of conformational changes. Studies with heteromeric channels incorporating a key lysine mutation (K68A) in the ATP binding site demonstrate that normally three molecules of ATP activate the receptor. The time-course of VCF responses to ATP, 2'-deoxy ATP, 3'-deoxy ATP, Ap5A and αßmeATP were agonist dependent. Comparing the properties of the deoxy forms of ATP demonstrated the importance of the 2' hydroxyl group on the ribose ring in determining agonist efficacy consistent with MD simulations showing that it forms a hydrogen bond with the γ-phosphate oxygen stabilizing the U-shaped conformation. Comparison of the recovery of fluorescence on agonist washout, with channel activation to a second agonist application for the partial agonists Ap5A and αßmeATP, showed a complex relationship between conformational change and desensitization. These results highlight that different agonists induce distinct conformational changes, kinetics and recovery from desensitization at P2X1Rs.

Minimally invasive surgery for superior mesenteric artery syndrome: a case report and literature review.

INTRODUCTION: Superior mesenteric artery syndrome is a rare condition characterised by nausea, vomiting, postprandial pain, anorexia and early satiety. Conservative management is tried initially, but if this fails, surgery is indicated. There are few reports in the literature concerning superior mesenteric artery syndrome in children, and fewer still managed surgically by minimally invasive means. CASE PRESENTATION: A 12-year-old girl presented with weight loss, early satiety and vomiting after corrective scoliosis surgery. After upper gastrointestinal endoscopy, contrast study and computed tomography imaging, a diagnosis of superior mesenteric artery syndrome was made. Conservative management by nasojejunal feeding failed; therefore, a laparoscopic duodeno-jejunostomy was undertaken. At follow-up, her symptoms had improved. CONCLUSION: This report describes the youngest child to undergo laparoscopic duodeno-jejunostomy for superior mesenteric artery syndrome. Laparoscopic duodeno-jejunostomy appears to be the most widely employed and reliable minimally invasive approach to superior mesenteric artery syndrome with a high success rate and acceptably low complication rate.

Is Screening of Intestinal Foregut Anatomy in Heterotaxy Patients Really Necessary?: A Systematic Review in Search of the Evidence.

OBJECTIVE: (1) Is screening of intestinal rotational anatomy obligatory in "asymptomatic" patients with heterotaxy? (2) Does detection of an anomaly warrant surgical correction? SUMMARY OF BACKGROUND DATA: Heterotaxy is an abnormal arrangement of thoraco-abdominal viscera across a left-to-right axis. Intestinal rotational anomalies are frequent among patients with heterotaxy, but debate exists as to whether they are benign in nature, requiring careful observation alone, or if surgical correction is warranted to prevent obstruction or midgut volvulus. METHODS: A systematic review [according to PRISMA guidelines] was conducted using CINAHL, EMBASE, Medline, and Cochrane Databases. Article quality was assessed using MINORS criteria. Conference proceedings and unpublished data were screened additionally. RESULTS: Nineteen studies met the eligibility criteria but reporting was adequate for 9. All were observational studies. These included a total of 414 patients managed expectantly, that is, "asymptomatic patients" in whom no intestinal rotation screening was undertaken (group A), 191 cases in whom screening was performed routinely (group B), and 92 patients considered "symptomatic" of potential rotational anomalies and therefore underwent imaging or laparotomy (group C). In group A, 1 patient developed symptoms attributable to malrotation in whom laparotomy confirmed the diagnosis (0.24%). Among groups B and C, 151 had Ladd's operations (53%) and 14 cases of malrotation with obstruction or volvulus were described (4.9%), of which 2 "symptomatic patients" died before laparotomy. Overall surgical complication rate was 17% with 30-day mortality rate of 2.6% to 4.6%. CONCLUSION: The evidence base for screening "asymptomatic" patients is weak especially considering the life-limiting comorbidities.

Pyrrole-Imidazole Polyamides: Manual Solid-Phase Synthesis.

Pyrrole-imidazole polyamides (PAs) are a family of DNA-binding peptides that bind in the minor groove of double-stranded DNA (dsDNA) in a sequence-selective, programmable fashion. This protocol describes a detailed manual procedure for the solid-phase synthesis of this family of compounds. The protocol entails solution-phase synthesis of the Boc-protected pyrrole (Py) and imidazole (Im) carboxylic acid building blocks. This unit also describes the importance of choosing the appropriate condensing agent to form the amide linkages between each building block. Finally, a monomeric coupling protocol and a fragment-based approach are described that delivers PAs in 13% to 30% yield in 8 days.

Pyrrole-Imidazole Polyamides: Automated Solid-Phase Synthesis.

In this unit, the fully automated solid-phase synthetic strategy of hairpin Py-Im polyamides is described using triphosgene (BTC) as a coupling agent. This automated methodology is compatible with all the typical building blocks, enabling the facile synthesis of polyamide libraries in 9% to 20% yield in 3 days.

Heterotaxy and intestinal rotation anomalies: 20 years experience at a UK regional paediatric surgery centre.

BACKGROUND: The association of heterotaxy with intestinal rotation anomalies is well described. However debate exists with regard optimal management notably should 'asymptomatic' bowel rotation anomalies undergo operation? The present study therefore sought to determine: (1) the risk(s) of volvulus in patients diagnosed with heterotaxy and (2) define morbidity associated with operation for 'asymptomatic' anomalies in a fragile patient cohort with co-existent congenital heart disease. METHODS: Medical case record reviews of ALL heterotaxy patients born during January 1993-December 2013 and attending a UK paediatric centre were analyzed. RESULTS: Of a total of 92 patients, 16 (17.4%) cases underwent foregut imaging studies. Three examinations were performed in 'symptomatic' patients. Twelve studies reported 'abnormal anatomy' with only five patients undergoing surgical correction. No complication(s) were recorded after Ladd's operation to correct defects. A single fatality occurred within 30 days postoperatively from cardiac failure. In 87 patients in whom Ladd's operation was not undertaken, no single patient developed intestinal volvulus (median length of follow-up 27.2 months, total 446.1 person years). CONCLUSION: This study strongly supports a 'watchful waiting' policy for heterotaxy patients. Many children who ultimately die from heart disease may avoid unnecessary abdominal surgery.