The Diagnostic Utility of Lip Biopsy in Paediatric Crohn's Disease: A 10-year Single-centre Retrospective Study.

BACKGROUND: Oral manifestations of paediatric Crohn's disease (CD) are reported in up to 60% of cases. Lip biopsy can be used to histologically diagnose oral CD. We evaluated the utility of lip biopsy in children under initial investigation for potential CD. METHODS: A 10-year retrospective review of electronic patient records at a single tertiary paediatric surgery centre was performed. All patients aged ≤16 years who underwent lip biopsy were included. Clinical features, histology, and diagnostic details were extracted. RESULTS: Forty-two children underwent lip biopsy. Median age at biopsy was 13.3 years (11.0-14.9). Final diagnosis was CD in 21/42 (50%) children, indeterminant colitis in 3/42 (7%), orofacial granulomatosis (OFG) in 3/42 (7%), coeliac disease in 1/42 (2%), and eosinophilic oesophagitis in 1/42 (2%). Thirteen children (31%) received no formal diagnosis. The most common symptoms reported were oral ulceration (33/42, 79%), lip swelling (21/42, 50%), and abdominal pain (19/42, 45%). Lip biopsy histology was normal in 11/42 (26%). In 24/42 (57%), non-granulomatous inflammation was seen. In 7/42 (17%) lip biopsy identified granulomatous inflammation: three (7%) had endoscopic biopsies concordant for CD, three (7%) had negative endoscopic biopsies but were diagnosed with CD, and one was diagnosed with OFG (2%). Sensitivity was 29% and specificity was 95%. CONCLUSION: Lip biopsy has low sensitivity but high specificity for diagnosing CD. Lip biopsy diagnosed CD in 7% when endoscopic biopsies were negative, enabling treatment. LB is a useful diagnostic test for CD in children presenting with oral symptoms. LEVEL OF EVIDENCE: III.

Congenital duodenal obstruction repair with and without transanastomotic tube feeding: a systematic review and meta-analysis.

OBJECTIVE: To determine the impact of transanastomotic tube (TAT) feeding in congenital duodenal obstruction (CDO). DESIGN: Systematic review with meta-analysis. PATIENTS: Infants with CDO requiring surgical repair. INTERVENTIONS: TAT feeding following CDO repair versus no TAT feeding. MAIN OUTCOME MEASURES: The main outcome was time to full enteral feeds. Additional outcomes included use of parenteral nutrition (PN), cost and complications from either TAT or central venous catheter. Meta-analyses were undertaken using random-effects models (mean difference (MD) and risk difference (RD)), and risk of bias was assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. RESULTS: Twelve out of 373 articles screened met the inclusion criteria. All studies were observational and two were prospective. Nine studies, containing 469 infants, were available for meta-analysis; however, four were excluded due to serious or critical risk of bias. TAT feeding was associated with reduced time to full enteral feeds (-3.34; 95% CI -4.48 to -2.20 days), reduced duration of PN (-6.32; 95% CI -7.93 to -4.71 days) and reduction in nutrition cost of £867.36 (95% CI £304.72 to £1430.00). Other outcomes were similar between those with and without a TAT including inpatient length of stay (MD -0.97 (-5.03 to 3.09) days), mortality (RD -0.01 (-0.04 to 0.01)) and requirement for repeat surgery (RD 0.01 (-0.03 to 0.05)). CONCLUSION: TAT feeding following CDO repair appears beneficial, without increased risk of adverse events; however, certainty of available evidence is low. Earlier enteral feeding and reduced PN use are known to decrease central venous catheter-associated risks while significantly reducing cost of care. PROSPERO REGISTRATION NUMBER: CRD42022328381.

Tunnelled external versus implanted port central venous catheters in paediatric oncology: a systematic review and meta-analysis.

OBJECTIVE: To evaluate and compare the complications associated with tunnelled external and implanted port (PORT) central venous catheters (CVCs) in children with cancer. DESIGN: A systematic review in accordance with PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines was performed (pre-registered on PROSPERO: CRD42022300869). MEDLINE, Web of Science and the Cochrane Library databases were searched. PATIENTS: Patients ≤18 years of age with haematological or solid malignancies. INTERVENTIONS: Studies comparing tunnelled external and PORT CVCs. MAIN OUTCOMES MEASURES: Infection, mechanical failure, thrombosis, bleeding, acceptability, quality of life (QoL), cost, premature removal, and days from insertion to removal for any reason. RESULTS: Twenty-three observational studies met the inclusion criteria, representing 6644 devices and 6032 patients. Tunnelled external CVCs were associated with an increased risk for systemic infection (OR 2.10, 95% CI 1.59 to 2.77, p<0.001, 16 studies, 3425 devices). There was no significant difference in the risk of localised infection (OR 1.15, 95% CI 0.66 to 2.01, p=0.62, 5 studies, 979 devices). Tunnelled external CVCs were also associated with a significantly increased risk of mechanical complications (OR 2.47, 95% CI 1.21 to 5.05, p=0.01, 11 studies, 2187 devices) and premature device removal (OR 3.24, 95% CI 1.28 to 8.22, p=0.01, 6 studies, 1514 devices). CONCLUSION: This study shows that PORTs associate with a reduced risk of infectious and mechanical complications, and a lower overall risk of removal, compared with tunnelled external CVCs in children with cancer. Further work is required to confirm these findings in a prospective randomised trial and to compare cost implications and acceptability to patients and caregivers.

Use of trans-anastomotic tubes in congenital duodenal obstruction.

AIM: Despite data to suggest benefit of trans- anastomotic tube (TAT) feeding in infants following repair of congenital duodenal obstruction (CDO), TAT usage is limited. We aimed to report a large series of infants with CDO treated with or without TAT in order to improve the evidence underlying this simple intervention. METHOD: Single centre retrospective review of all infants CDO over a 20-year period (January 1999 - November 2020, inclusive). Important outcomes were compared between infants treated with or without TAT. Data are median [IQR]. RESULTS: Ninety-six infants were included. A TAT was placed in 54 infants (56%). Median time to full enteral feed was significantly shorter in the TAT group (6 [5-8] days vs 10 [7.5-12], p <0.001). Time to first feed was shorter in the TAT group (2 [2-2.8] days vs 3 [2-5], p<0.001). Significantly fewer infants with a TAT placed received a central venous catheter (CVC, 15% vs 76%, p <0.001). Infants without a TAT received parenteral nutrition (PN) for longer (0 [0-0] vs 7 [0-11] days, p <0.001). There was no change in length of stay between TAT and no TAT group (16 [13-21.8] vs 15 [12-21.8] days, p = 0.722). Eight infants (15%) in the TAT group required a CVC and PN. One infant in the TAT group developed a perforation that required surgical management and nine infants in the non-TAT group had complications related to the CVC (21%), including one infant that required general anaesthetic for tunnelled central line placement (2.3%). CONCLUSION: In infants with CDO, TAT use was associated with earlier establishment of full enteral feeds, reduced need for CVC and PN and reduced complications. Further research should focus on the barriers to wider use of TAT by surgeons and neonatologists in infants with CDO.

Development and validation of a novel 3D-printed simulation model for open oesophageal atresia and tracheo-oesophageal fistula repair.

BACKGROUND: The role of simulation training in paediatric surgery is expanding as more simulation devices are designed and validated. We aimed to conduct a training needs assessment of UK paediatric surgical trainees to prioritise procedures for simulation, and to validate a novel 3D-printed simulation model for oesophageal atresia and tracheo-oesophageal fistula (OA-TOF) repair. METHODS: A questionnaire was sent to UK trainee paediatric surgeons surveying the availability and utility of simulation. The operation ranked as most useful to simulate was OA-TOF repair. 3D-printing techniques were used to build an OA-TOF model. Content, face and construct validity was assessed by 40 paediatric surgeons of varying experience. RESULTS: Thirty-four paediatric surgeons completed the survey; 79% had access to surgical simulation at least monthly, and 47% had access to paediatric-specific resources. Perceived utility of simulation was 4.1/5. Validation of open OA-TOF repair was conducted by 40 surgeons. Participants rated the model as useful 4.9/5. Anatomical realism was scored 4.2/5 and surgical realism 3.9/5. The model was able to discriminate between experienced and inexperienced surgeons. CONCLUSION: UK paediatric surgeons voted OA-TOF repair as the most useful procedure to simulate. In response we have developed and validated an affordable 3D-printed simulation model for open OA-TOF repair.

Physical Determinants of Vitamin D Photosynthesis: A Review.

Vitamin D synthesis by exposure of skin to solar ultraviolet radiation (UVR) provides the majority of this hormone that is essential for bone development and maintenance but may be important for many other health outcomes. This process, which is the only well-established benefit of solar UVR exposure, depends on many factors including genetics, age, health, and behavior. However, the most important factor is the quantity and quality of UVR reaching the skin. Vitamin D synthesis specifically requires ultraviolet B (UVB) radiation that is the minority component (<5%) of solar UVR. This waveband is also the most important for the adverse effects of solar exposure. The most obvious of which is sunburn (erythema), but UVB is also the main cause of DNA damage to the skin that is a prerequisite for most skin cancers. UVB at the Earth's surface depends on many physical and temporal factors such as latitude, altitude, season, and weather. Personal, cultural, and behavioral factors are also important. These include skin melanin, clothing, body surface area exposed, holiday habits, and sunscreen use. There is considerable disagreement in the literature about the role of some of these factors, possibly because some studies have been done by researchers with little understanding of photobiology. It can be argued that vitamin D supplementation obviates the need for solar exposure, but many studies have shown little benefit from this approach for a wide range of health outcomes. There is also increasing evidence that such exposure offers health benefits independently of vitamin D: the most important of which is blood-pressure reduction. In any case, public health advice must optimize risk versus benefit for solar exposure. It is fortunate that the individual UVB doses necessary for maintaining optimal vitamin D status are lower than those for sunburn, irrespective of skin melanin. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Therapeutic strategies for stricturing Crohn's disease in childhood: a systematic review.

PURPOSE: Childhood stricturing Crohn's disease (CD) has significant morbidity. Interventions including resection, stricturoplasty and endoscopic balloon dilatation (EBD) are often required. Optimal intervention modality and timing, and use of adjuvant medical therapies, remains unclear. We aim to review the therapies used in paediatric stricturing CD. METHODS: A systematic review in accordance with PRISMA was performed (PROSPERO: CRD42020164464). Demographics, stricture features, interventions and outcomes were extracted. RESULTS: Fourteen studies were selected, including 177 patients (183 strictures). Strictures presented at 40.6 months (range 14-108) following CD diagnosis. Medical therapy was used in 142 patients for an average of 20.4 months (2-36), with a complete response in 11 (8%). Interventions were undertaken in 138 patients: 53 (38%) resections, 39 (28%) stricturoplasties, and 17 (12%) EBD. Complications occurred in 11% of resections, versus 15% stricturoplasties, versus 6% EBD (p = 0.223). At a median follow-up of 1.9 years (interquartile range 1.2-2.4) pooled stricture recurrence was 22%. Resection had 9% recurrence, versus 38% stricturoplasty, versus 47% EBD (p < 0.001). CONCLUSIONS: Resection is associated with a low incidence of recurrence and complications. There remains a paucity of evidence regarding adjuvant medical therapy and the role of EBD. We propose a minimum reported dataset for interventions in paediatric stricturing CD.

The weekend effect - How can it be mitigated? Introduction of a consultant-delivered emergency general surgical service.

BACKGROUND: Poorer patient outcomes for emergency general surgery have been observed in patients admitted to hospital over the weekend. This paper reports the outcomes of a Consultant-delivered service model for weekend admissions and its impact for patients undergoing emergency laparotomy. METHODS: Operative data was analysed from a prospectively collected database over 5-years. Primary outcome measures were 30-day all-cause mortality and Clavien-Dindo class ≥2 morbidity. Secondary outcomes included time from admission to diagnostic imaging and time to surgery, post-operative length of stay and requirement for Intensive Care Unit admission. RESULTS: 263 patients underwent an emergency laparotomy. Overall 30-day mortality was 4.6% and all-cause morbidity was 55.9%. The most common indications for laparotomy were mechanical small bowel obstruction (32.7%) and hollow viscus perforation (30.4%) of the 263 emergency laparotomies, 92 patients in the cohort were weekend admissions (Saturday or Sunday). There was no significant difference amongst patients admitted during the weekend in ASA grade, age, gender, or proportion of patients receiving a pre-operative computed tomography scan, when compared to those during the week. Compared to weekdays, weekend admission was not associated with a significant difference in mortality (5.3% and 3.3%, respectively p = 0.458), all-cause morbidity (p = 0.509), post-operative length of stay (p = 0.681), or Intensive Care Unit admission (p = 0.761). CONCLUSION: A Consultant Surgeon delivered emergency service can avoid the poor patient outcomes associated with weekend admissions and the 'weekend effect'.

Adult Presentations of Congenital Midgut Malrotation: A Systematic Review.

BACKGROUND: Adult midgut malrotation is a rare cause of an acute abdomen requiring urgent intervention. It may also present in the non-acute setting with chronic, non-specific symptoms. The objective of this study is to identify the clinical features, appropriate investigations and current surgical management associated with adult malrotation. METHODS: A systematic review was conducted according to PRISMA guidelines, identifying confirmed cases of adult malrotation. Patient demographics, clinical features, investigation findings and operative details were analysed. RESULTS: Forty-five reports met the inclusion criteria, totalling 194 cases. Mean age was 38.9 years (n = 92), and 52.3% were male (n = 130). The commonest presenting complaints were abdominal pain (76.8%), vomiting (35.1%) and food intolerance (21.6%). At least one chronic symptom was reported in 87.6% and included intermittent abdominal pain (41.2%), vomiting (12.4%) and obstipation (11.9%). Computerised tomography scanning was the most frequent imaging modality (81.4%), with a sensitivity of 97.5%. The whirlpool sign was observed in 30.9%; abnormalities of the superior mesenteric axis were the commonest finding (58.0%). Ladd's procedure was the most common surgical intervention (74.5%). There was no significant difference in resolution rates between emergency and elective procedures (p = 0.46), but length of stay was significantly shorter for elective cases. (p = 0.009). There was no significant difference in risk of mortality, or symptom resolution, between operative and conservative management (p = 0.14 and p = 0.44, respectively). CONCLUSION: Malrotation in the adult manifests with chronic symptoms and should be considered as a differential diagnosis in patients with abdominal pain, vomiting and food intolerance.

Referrers' point of view on the referral process to neurosurgery and opinions on neurosurgeons: a large-scale regional survey in the UK.

OBJECTIVES: There is an increased reliance on online referral systems (ORS) within neurosurgical departments across the UK. Opinions of neurosurgeons on ORS are extensively reported but those of referrers have hardly been sought. Our study aims at ascertaining our referring colleagues' views on our ORS and its impact on patient care, their opinions on neurosurgeons and how to improve our referral process. SETTING: 14 district general hospitals and one teaching hospital. PARTICIPANTS: 641 healthcare professionals across a range of medical and surgical specialties including doctors of all grades, nurses and physiotherapists. Survey responses were obtained by medical students using a smartphone application. RESULTS: Although 92% of respondents were aware of the ORS, 74% would routinely phone the on-call registrar either before or after making referrals online. The majority (44%) believed their call to relate to a life-threatening emergency. 62% of referrers considered the ORS helpful in informing patients' care and 48% had a positive opinion of their interaction with neurosurgical registrars. On ways to improve the ORS, 50% selected email/text confirmation of response sent to referrers and 16% to referring consultants. CONCLUSION: Our results confirm that referrers feel that using our ORS positively impacts patient care but that it remains in need of improvement in order to better suit our colleagues' needs when it comes to managing neurosurgical patients. We feel that the promotion of neurosurgical education and mitigation of the effects of adverse workplace human factors are likely to achieve the common goal of neurosurgeons and referrers alike: a high standard in patient care.

Ubiquitous Chromatin-opening Elements (UCOEs): Applications in biomanufacturing and gene therapy.

Ubiquitous Chromatin-opening Elements (UCOEs) are defined by their ability to consistently confer stable, site of integration-independent transgene expression that is proportional to copy number, including from within regions of heterochromatin such as centromeres. UCOEs structurally consist of methylation-free CpG islands encompassing single or dual divergently-transcribed housekeeping gene promoters. Since their discovery in 1999, UCOEs and their sub-fragments have found applications in areas of biotechnology requiring stable, reproducible, and high levels of gene expression. This review recounts the discovery of UCOEs and examines their current and future applications in protein therapeutic biomanufacturing and gene therapy.