Background and objectives Cystinuria is a rare inherited renal stone disease. Mutations in the amino acid exchanger System b 0,+ , the two subunits of which are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. The work analyzed the epidemiology of cystinuria and the influence of mutations in these two genes on disease severity in a United Kingdom cohort.Design, setting, participants, & measurements Prevalent patients were studied from 2012 to 2014 in the northeast and southwest of the United Kingdom. Clinical phenotypes were defined, and genetic analysis of SLC3A1 and SLC7A9 combining Sanger sequencing and multiplex ligation probe-dependent amplification was performed.Results In total, 76 patients (42 men and 34 women) were studied. All subjects had proven cystine stones. Median age of presentation (first stone episode) was 24 years old, but 21% of patients presented after 40 years old. Patients had varied clinical courses, with 37% of patients having $10 stone episodes; 70% had evidence of CKD, and 9% had reached ESRD as a result of cystinuria and its complications. Patients with cystinuria received a variety of different therapies, with no obvious treatment consensus. Notably, 20% of patients had staghorn calculi, with associated impaired renal function in 80% of these patients. Genetic analysis revealed that biallelic mutations were present in either SLC3A1 (n=27) or SLC7A9 (n=20); 22 patients had only one mutated allele detected (SLC3A1 in five patients and SLC7A9 in 17 patients). In total, 37 different mutant variant alleles were identified, including 12 novel mutations; 22% of mutations were caused by large gene rearrangements. No genotypephenotype association was detected in this cohort.Conclusions Patients with cystinuria in the United Kingdom often present atypically with staghorn calculi at $40 years old and commonly develop significant renal impairment. There is no association of clinical course with genotype. Treatments directed toward reducing stone burden need to be rationalized and developed to optimize patient care.

Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. MethodsWe did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. FindingsWe included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58•0%) were male. Median gestational age at birth was 38 weeks (IQR 36-39) and median bodyweight at presentation was 2•8 kg (2•3-3•3). Mortality among all patients was 37 (39•8%) of 93 in low-income countries, 583 (20•4%) of 2860 in middle-income countries, and 50 (5•6%) of 896 in high-income countries (p<0•0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90•0%] of ten in lowincome countries, 97 [31•9%] of 304 in middle-income countries, and two [1•4%] of 139 in high-income countries; p≤0•0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2•78 [95% CI 1•88-4•11], p<0•0001; middle-income vs high-income countries, 2•11 [1•59-2•79], p<0•0001), sepsis at presentation (1•20 [1•04-1•40], p=0•016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4-5 vs ASA 1-2, 1•82 [1•40-2•35], p<0•0001; ASA 3 vs ASA 1-2, 1•58, [1•30-1•92], p<0•0001]), surgical safety checklist not used (1•39 [1•02-1•90], p=0•035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1•96, [1•4...

Normal cerebral function is dependent upon an adequate and continuous supply of oxygen. This study calculated cerebral blood flow based on assessment of the right middle cerebral artery (MCA) velocity (MCAVel) and MCA diameter (MCADiam) by trans-cranial Doppler and trans-cranial Duplex in normoxia, during acute exposure to 12% normobaric hypoxia for up to 6 hours, and after 3 days exposure to the equivalent altitude, 4392 m, in nine subjects. Mean (SD) MCAVel increased both after 6 hours hypoxia from 76.8 (11.4) to 97.2 (17.4) cms/sec (p<0.001), and after 3 days at altitude from 68.1 (7.5) [sea level] to 76.2 (10.2) [4392 m] (p=0.015). MCADiam increased from 5.07 (0.6) to 6.1 (0.6) mm (p<0.001) after 6 hours of 12% hypoxia. Calculated mean MCA blood flow increased after 6 hours of 12% hypoxia from 5.0 (0.6) mL/sec to 8.9 (1.2) mL/sec, but there was no difference between sea level and 4392 m. Calculated mean cerebral oxygen delivery increased from 72.4 (14.4) to 107 (20.1) mL/sec (p<0.001) after 6 hours of 12% hypoxia and was maintained unchanged at 4392 m. An increase in MCA caliber, rather than blood velocity, was a major contributor to increased oxygen delivery accompanying within the first few hours of exposure to acute hypoxia. During more long-term exposure, increases in MCA velocity and a rise in hemoglobin appeared to be the more important mechanisms in maintaining cerebral oxygen delivery. The implication of this observed change in MCA diameter questions the widely held assumption that MCA velocity is a surrogate for flow during acute hypoxic exposure.

Summary Background Fasciola hepatica (liver fluke) affects grazing animals including horses but the extent to which it affects UK horses is unknown. Objectives To define how liver fluke affects the UK horse population. Study design Descriptive, cross‐sectional, observational study. Methods An F. hepatica excretory‐secretory antibody detection ELISA with a diagnostic sensitivity of 71% and specificity of 97% was validated and used to analyse serum samples. An abattoir study was performed to determine prevalence. A case‐control study of 269 horses compared fluke exposure between horses with liver disease and controls. Data on clinical signs and blood test results were collected for sero‐positive horses. Genotyping of adult fluke was used to produce a multilocus genotype for each parasite. Results Four (2.2%) of 183 horses registered in the UK, sampled in the abattoir, had adult flukes in the liver, and the sero‐prevalence of F. hepatica was estimated as 8.7%. In the case‐control study, horses showing signs consistent with liver disease had significantly higher odds of testing positive for F. hepatica on ELISA than control horses. In 23 sero‐positive horses, a range of non‐specific clinical signs and blood test abnormalities was reported, with a third of the horses showing no signs. Genotypic analysis of liver flukes from horses provided evidence that these came from the same population as flukes from sheep and cattle. Main limitations Bias could have arisen in the prevalence and case‐control studies due to convenience sampling methods, in particular the geographic origin of the horses. Only a small number of horses tested positive so the data on clinical signs are limited. Conclusions Exposure to liver fluke occurs frequently in horses and may be an under‐recognised cause of liver disease. Flukes isolated from horses are from the same population as those found in ruminants. When designing and implementing parasite control plans, fluke should be considered, and horses should be tested if appropriate.

Background Magnets and button batteries (BBs) are dangerous ingested foreign bodies in children. The scale and consequences of this public health issue in the UK are unknown. This study aims to report the current management strategies and outcomes associated with paediatric magnet and BB ingestion in the UK. Methods This multicentre, retrospective observational study involved 13 UK tertiary paediatric surgery centres. Children aged under 17 years, admitted between 1 October 2019 and 30 September 2020, following magnet, or BB ingestion were included. Demographics, investigations, management, and complications were recorded. Results In total, 263 patients were identified, comprising 146 (55.5 per cent) magnet, 112 (42.6 per cent) BB, and 5 (1.9 per cent) mixed magnet BB ingestions. Median (interquartile range) age was 4.8 (2.0–9.1) years and 47.5 per cent were female. In the magnet group, 38 (26.0 per cent) children swallowed single magnets, 3 of whom underwent endoscopic retrieval for oesophageal or gastric impaction. Of the 108 (74.0 per cent) children who swallowed multiple magnets, 51 (47.2 per cent) required endoscopic or surgical intervention, predominantly for failure of magnets to progress on serial imaging. Bowel perforations occurred in 10 children (9.3 per cent). Younger age and ingestion of greater numbers of multiple magnets were independently associated with surgery. BB ingestion caused morbidity in 14 children (12.5 per cent) and life-threatening injuries in two (1.8 per cent); the majority were caused by oesophageal BBs (64.3 per cent). Conclusion Multiple magnet and BB ingestions are associated with significant morbidity. Action must be taken at an international level to regulate the sale of magnets and BBs, and to raise awareness of the risks that these objects pose to children.

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Introduction: Infantile hypertrophic pyloric stenosis (IHPS) is a common surgical condition, but there are no guidelines regarding preoperative fluid resuscitation. Our aim was to evaluate a novel consensus care pathway for IHPS, incorporating a standardized fluid and electrolyte replacement regime. Methods: One hundred patients were initially reviewed and compared to thirty-three patients following the introduction of a clinical pathway, whereby infants requiring electrolyte correction received 150 ml/kg/24 h of 0.45% saline, 5% dextrose and 10 mmol KCl, with systematic blood sampling until correction was achieved. We measured time to electrolyte correction, time to surgery and total length of hospitalization. Data were described using the median and interquartile range, and differences between the groups' categorical and continuous data were described using Chisquared and the Mann-Whitney U-tests, respectively. Results: Time in hours taken to correct electrolytes was reduced: 25(16.5-42) versus 9.5(4.5-24.75) p ¼ 0.004. Time to surgery from admission in uncorrected patients decreased from 50(40.25-66.75) to 39(28.75-41.75) p ¼ 0.018. Subsequently, there was a reduction in total length of stay: 94(71-93.5) versus 75(64.5-93.5) p ¼ 0.025. Parental satisfaction increased from 77% in the pre-pathway group to 83% in the pathway group. Conclusion: A consensus care pathway for IHPS reduces the time taken to correct preoperative electrolyte abnormalities, decreases length of hospitalization and improves parental satisfaction.