The increasing burden of the 2-week wait colorectal cancer pathway in a single centre: the impact of faecal immunochemical tests.

INTRODUCTION: Two-week wait (TWW) volume and colorectal cancer (CRC) detection pose an increasing challenge for NHS cancer services. Primary aims were to assess the introduction of faecal immunochemical tests (FIT) into clinical practice at our centre, the impact on TWW referral volume and CRC diagnoses, and to provide an update to previously published work. A secondary aim was to correlate FIT value and investigation. METHODS: TWW CRC data following incorporation of FIT into clinical practice were analysed (1 June 2019-31 July 2021). Parameters assessed were monthly referral volume, CRC detection, primary care FIT volume and secondary care investigations. Referrals and CRC detection rates were compared with previously published data (2009-2019). Data relating to primary care FIT were collated from Berkshire and Surrey Pathology Services. RESULTS: TWW referrals increased 360% (2009-2020). CRC incidence decreased from 8.87% to 3.24%. Following incorporation into clinical practice, primary care FIT requests have increased to >450/month and accompanied 1,722/4,796 referrals. CRC incidence is static (3-4%). Patients with FIT <10µg Hb/g faeces undergo radiological imaging more commonly, whereas FIT-positive patients are more likely to undergo endoscopy, although the difference is not statistically significant. CONCLUSIONS: No significant change in CRC diagnosis was observed, despite increasing TWW referrals. Increasing utilisation of FIT in both primary and secondary care has helped maintain CRC detection while avoiding diagnostic delay. This study supports growing evidence highlighting the value of FIT in triage, referral and TWW investigation. FIT appears increasingly important for allocating secondary care resources (endoscopy), while guiding primary care referral. Additional low-cost strategies to determine prioritisation or reassurance (e.g. repeat FIT) require further evaluation.

Non-pain-related complaints of paediatric patients after dental treatment under general anaesthesia.

AIM: To investigate the prevalence, duration, and severity of non-pain-related complaints after dental treatment under general anaesthesia (DTGA) and to identify correlating factors from patient's characteristics and treatment. METHODS: Parents/caregivers of children treated under general anaesthesia were asked to fill in a dichotomous questionnaire during hospitalisation and the postoperative week. Several complaints were evaluated in relation to factors associated with dental treatment and general anaesthesia. CONCLUSION: Postoperative morbidity after DTGA is common. Patients and their parents should be informed about the possibility of experiencing mild to moderate complaints, and adverse events that may last up to 7 days.

New method of remnant closure during distal pancreatectomy.

PURPOSE: Pancreatic fistula following distal pancreatectomies still remains a relevant problem. The present study describes our first series with a new method of pancreatic remnant closure. METHODS: A free fascia-peritoneum graft - harvested from the internal rectus sheet - was fixed onto the pancreatic stump by one circular stitch. The method was applied in 18 cases. RESULTS: The postoperative hospital stay was 8 days in average. No clinically relevant postoperative pancreatic fistula (CR-POPF) developed. The morbidity rate was 39%, mostly Clavien-Dindo Grade II types. There was no reoperation or mortality. CONCLUSION: The first series showed advantageous results with our method. Certainly, further studies are needed for the evaluation of this new and promising technique.

Pain-related complaints of paediatric patients after dental treatment under general anaesthesia.

AIM: To identify factors related to postoperative pain and to recognise strategies to reduce this pain after dental treatment under general anaesthesia. METHODS: Cross-sectional observational study. Children treated under general ansesthesia reported pain daily using the Wong Baker FACES® Pain Rating Scale. Their parents/caregivers filled in a related Yes/No questionnaire during hospitalisation and the first postoperative week. The duration and severity of pain were evaluated in relation to various factors. CONCLUSION: A well-established protocol is indicated to reduce operation time. Patients and their parents should be informed about the possibility of constantly subsiding postoperative pain that may last for a week. As additional local anaesthesia during general anaesthesia (GA) does not provide postoperative pain reduction in deciduous tooth extraction cases, its administration could be omitted.

Gastric outlet obstruction secondary to a wandering spleen: systematic review and surgical management of a case.

INTRODUCTION: A wandering spleen occurs when laxity or absence of the suspensory ligaments allows migration throughout the abdomen. Gastric outlet obstruction resulting from this abnormality is rare. We present a systematic literature search and a case that was managed successfully with surgical intervention at our centre. METHODS: A systematic search of the PubMed, Embase™, Medline® and Google Scholar™ databases was carried out employing the combined search terms "gastric outlet obstruction" AND "wandering spleen". Six results were included for final analysis. RESULTS: All six search results described a single case each. Patients underwent surgical management (open or laparoscopic) after initial investigation utilising a range of modalities. There were no mortalities reported at 90 days. The single case we present was complicated by gastric perforation; the patient made a successful recovery following open splenopexy and stapled wedge resection of the stomach. CONCLUSIONS: A wandering spleen is a rare diagnosis and there are only six reported cases of gastric outlet obstruction secondary to a wandering spleen in the literature. None report associated gastric perforation. There are a variety of presenting symptoms, intraoperative findings and operative techniques used to address the gastrosplenic abnormality. The case reported by our centre adds to this limited evidence base and demonstrates a successful outcome from definitive surgical management. We highlight the need to seek early gastro-oesophageal expertise if any gastric pathology is found together with anatomical abnormality of the spleen.

Patient-reported outcome measures show FIT as an acceptable investigation to rule out colorectal cancer in the two-week wait cohort.

INTRODUCTION: Use of faecal immunochemical testing (FIT) for symptomatic patients is increasing. FIT is recommended as a triage tool from primary care to the two-week wait (TWW) suspected cancer pathway, but there is still little known about patient attitudes. AIM: The aim of this study was to explore patient opinions of FIT and how it might be applied in the TWW pathway. METHODS: A telephone survey was conducted for patients from the TWW pathway who had undergone both conventional colonic investigation and FIT. Five questions explored expectations, attitudes towards results and experience of the investigations using a Likert scale 1-5. Differences in opinion were compared using median and mode scores and visualised using bar charts. RESULTS: One hundred and nine TWW patients agreed to answer the five questions. All had taken a stool sample for FIT, 50 underwent colonoscopy, 51 had a CT colonography and 8 underwent flexible sigmoidoscopy. Most patients (85%) scored 5 (completely satisfied) with these conventional colonic investigation methods they underwent for ruling out colorectal cancer (median 5). However, 30% of patients scored 5 (completely satisfied) if using a negative FIT to not require additional colonic investigation. The median score to perform FIT was 5 (very easy) compared with a median of 4 (easy) to undergo the other colonic investigations. CONCLUSIONS: Symptomatic patients can perform FIT with little difficulty, and often would have been happy to avoid conventional colonic investigations with a negative result. However, shared decision-making should be employed to identify those who would be dissatisfied with relying on FIT for further investigation decisions.

A systematic review of symptomatic hamartomas of the jejunum and ileum.

INTRODUCTION: Gastrointestinal hamartomas are rarely encountered benign growths made of an abnormal mixture of tissues normally found in the body where the growth occurs. Most hamartomas are asymptomatic and diagnosed incidentally. Evidence regarding symptomatic hamartomas of the jejunum and ileum is limited and restricted to anecdotal case reports. We aim to provide a contemporary overview to clarify various aspects linked to symptomatic hamartomas, helping aide management and clinical decision-making. METHODS: The search terms 'small bowel', 'small intestine', 'jejunum' and 'ileum' were combined with 'hamartoma'. Embase, Medline, PubMed searches and Google Scholar hand-searches were conducted. All English language papers from 1 January 2000 to 1 June 2020 were included. RESULTS: In total 39 cases were reviewed: 29 adults and 10 paediatric (0-16 years). Presenting symptoms included abdominal pain (87%), vomiting (56%), gastrointestinal bleeding (20.5%) and weight loss (5%); 36 of 39 cases (92%) presented as emergencies. Diagnostic investigations included: abdominal x-ray (49%), endoscopy (38%), computed tomography (56%), magnetic resonance imaging (5%), contrast study (15%) and video capsule endoscopy (5%). Initial management strategy was either open (30) or laparoscopic (7) surgery or endoscopy (2). All cases required surgery for definitive management. Twenty-five cases recorded hamartoma size, and mean maximum diameter was 3.56cm (1.2-8cm) with stricturing in seven cases. Nine of the 39 cases were associated with hamartomatous syndromes. Two mortalities were recorded. CONCLUSIONS: This is the first published review addressing symptomatic hamartomas of the jejunum and ileum. New data relating to demographic cohort, symptom profile, investigations, management strategies, and morbidity and mortality provide greater insight to those encountering this challenging clinical finding in the future.

A systematic review of chyle leaks and their management following axillary surgery.

INTRODUCTION: Chyle leaks following surgery to the axilla are seldom encountered with an incidence <0.7%. Management varies with no consensus in the literature. Injury to branching tributaries of the thoracic duct may require lengthy management at significant cost to patient and clinical team. This paper aims to provide an up-to-date review to support clinical management. METHODS: The term 'chyle' was combined with 'breast' or 'axilla.' EMBASE, Medline and PubMed database searches were conducted. All papers published in English were included with no exclusion date limits. RESULTS: 51 cases from 31 papers. All were female (mean age = 53.3yrs). 47/51 leaks were left-sided. 5/51 underwent sentinel node biopsy, 19/51 level II axillary node clearance (ANC), 23/51 level III ANC, 5/51 not specified. 59% (30/51) of leaks were identified within 2 postoperative days (mean = 3.3days). 96% initially managed conservatively: Drain = 38/51; low-fat diet = 34/51; compression bandaging = 20/51; Aspiration = 6/51. 40/51 (78%) were successfully managed conservatively, 11 patients returned to theater for secondary management. 7/11 recorded volumes >500mls/24 hrs before secondary surgery. Mean resolution time from initial surgery was 17.3days (range = 4-64days). No statistically significant difference (p = 0.72) in time to resolution between conservatively and surgically managed patients. CONCLUSIONS: Chyle leaks are rarely seen following axillary surgery. Aberrant thoracic duct anatomy represents the likeliest aetiology. We advocate early recognition and tailored individual management. Conservative management with non-suction drainage, low-fat diet and axillary compression bandaging appear effective where output <500ml/24 hrs. Secondary surgical management should be considered in high chylous output (<500mls/24 hrs) patients unresponsive to conservative measures. We propose a management algorithm to aide clinicians.

Application of a fast and cost-effective 'three-in-one' MMR ELISA as a tool for surveying anti-MMR humoral immunity: the Hungarian experience.

In Hungary, between February 2017 and July 2019, 70 confirmed measles cases were reported, raising questions about the adequacy of population-level immunity. Although the assumed vaccination coverage is ≥99%, in a recent study, we detected potential gaps in the anti-measles humoral immunity. In Hungary, according to a decree by the Ministry of Public Welfare, beginning from 2021, the healthcare provider should conduct a serosurvey of anti-measles protection levels of healthcare professionals. To facilitate the compliance with this requirement, we developed a quick 'three-in-one' or 'triple' MMR (measles, mumps and rubella) indirect ELISA (IgG); an assay format that is currently not available commercially. High throughput applicability of the 'three-in-one' ELISA was verified using 1736 sera from routine laboratory residual samples, using an automated platform (Siemens BEP 2000 Advance). Assay verification was performed by comparing the full antigen repertoire-based 'target' assay with in-house 'control' assays using recombinant viral antigen coatings, and by validated commercially available kits. Indirect immunofluorescence was used as an independent reference method. Data were analysed using OriginLab, IBM SPSS, RStudio and MedCalc. In case of measles, we combined our current results with previously published data (Ntotal measles = 3523). Evaluation of anti-mumps and anti-rubella humoral antibody levels was based on the measurement of 1736 samples. The lowest anti-measles seropositivity (79.3%) was detected in sera of individuals vaccinated between 1978 and 1987. Considering the antigen-specific seropositivity ratios of all samples measured, anti-measles, -mumps and -rubella IgG antibody titres were adequate in 89.84%, 91.82% and 92.28%, respectively. Based on the virus-specific herd immunity threshold (HIT) values (HITMeasles = 92-95%, HITMumps = 75-86%, HITRubella = 83-86), it can be stated that regarding anti-measles immunity, certain age clusters of the population may have inadequate levels of humoral immunity. Despite the potential gaps in herd immunity, the use of MMR vaccine remains an effective and low-cost approach for the prevention of measles, mumps and rubella infections.

Correlation of natural autoantibodies and cardiovascular disease-related anti-bacterial antibodies in pericardial fluid of cardiac surgery patients.

Our previous studies showed that anti-citrate synthase (anti-CS) immunoglobulin (Ig)M natural autoantibodies are present in healthy individuals without previous antigen stimulation, but no studies have investigated their presence in the pericardial fluid (PF). Therefore, we detected the natural anti-CS IgG/M autoantibody levels in plasma and PF of cardiac surgery patients and investigated their relationship with cardiovascular disease-associated bacterial pathogens. PF and blood samples of 22 coronary artery bypass graft (CABG) and 10 aortic valve replacement (AVR) patients were tested for total Ig levels, natural autoantibodies and infection-related antibodies using enzyme-linked immunosorbent assay (ELISA) and Luminex methods. The B cell subsets were measured by flow cytometry. The total Ig subclass levels were four to eight times lower in PF than in plasma, but the natural anti-CS IgM autoantibodies showed a relative increase in PF. The frequency of CD19+ B lymphocytes was significantly lower in PF than in blood (P = 0·01), with a significant relative increase of B1 cells (P = 0·005). Mycoplasma pneumoniae antibody-positive patients had significantly higher anti-CS IgM levels. In CABG patients we found a correlation between anti-CS IgG levels and M. pneumoniae, Chlamydia pneumoniae and Borrelia burgdorferi antibody titres. Our results provide the first evidence that natural autoantibodies are present in the PF, and they show a significant correlation with certain anti-bacterial antibody titres in a disease-specific manner.

A three-year follow-up study of the development of joint contractures in 131 patients with systemic sclerosis.

OBJECTIVES: To analyse the correlation between the number of joint-contractures and other major clinical findings in a follow-up study of 131 patients with systemic sclerosis (SSc). METHODS: The range of motion of joints (ROM), HAQ-DI, and the major clinical characteristics were assessed. RESULTS: A high frequency of contractures (ROM<75% of the normal) were present at baseline in small joints of the hand (82%), wrists (75%), and shoulders (50%). ROM of the dominant side hand was significantly more decreased compared to the non-dominant side. The number of the upper extremity contractures correlated positively with ESR (p<0.01), CRP (p<0.01), HAQ-DI (p<0.01), and negatively with forced vital capacity (FVC) (p<0.05). The number of contractures was not significantly different in cases with early (≤ 4 years) and late disease duration in both the limited and diffuse subgroups. During the three-year follow-up period, an increase in the number of joint contractures (ROM<75%) was associated with an increase of ESR, modified Rodnan's skin score, and the European Scleroderma Study Group Activity Index by multiple linear regression analysis. Univariate analysis over a six-year period demonstrated poor outcome in patients with more than ten contractures, or more than four contractures of unilateral hand-joints. CONCLUSIONS: Contractures predominantly develop during the early years following disease onset in both SSc subgroups. Inflammation and skin-involvement are significant contributing factors for the development of contractures. The dominant hand may be more pronouncedly impaired compared to the non-dominant side. A high number of joint-contractures might be an unfavourable prognostic factor in SSc.

High-voltage nanoimprint lithography of refractory metal films.

Local oxidation of metal, semiconductor, and polymer surfaces has provided a common basis from which to explore fundamental principles of nanolithography and prototype functional nanostructures for many years now. This article summarizes an investigation of local oxidation for iron and Group IV metal thin films using both scanning probe microscopy and high-voltage nanoimprinting methods. We illustrate how the underlying kinetics of metal oxidation in the presence of nitrogen, which is incorporated into the metal film during the growth process, is dramatically enhanced compared with that of single-crystal silicon. We then go on to demonstrate subsequent selective etching of latent features and a potential magnetic application.

Physical characterization methods for iron oxide contrast agents encapsulated within a targeted liposome-based delivery system.

Intact liposome-based targeted nanoparticle delivery systems (NDS) are immobilized by non-selective binding and characterized by scanning probe microscopy (SPM) in a fluid imaging environment. The size, size distribution, functionality, and stability of an NDS with a payload consisting of a super-paramagnetic iron oxide contrast agent for magnetic resonance imaging are determined. SPM results are combined with information obtained by more familiar techniques such as superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering, and electron microscopy. By integrating the methods presented in this work into the NDS formulation and manufacturing process, size-dependent statistical properties of the complex can be obtained and the structure-function relationship of individual, multi-component nanoscale entities can be assessed in a reliable and reproducible manner.

High-voltage SPM oxidation of ZrN: materials for multiscale applications.

Scanning probe microscope (SPM) oxidation was used to form zirconium oxide features on 200 nm thick ZrN films. The features exhibit rapid yet controlled growth kinetics, even in contact mode with 70 V dc applied between the probe tip and substrate. The features grown for times longer than 10 s are higher than 200 nm, and reach more than 1000 nm in height after 300 s. Long-time oxidation experiments and selective etching of the oxides and nitrides lead us to propose that as the oxidation reaches the silicon substrate, delamination occurs with the simultaneous formation of a thin layer of new material at the ZrN/Si interface. High-voltage oxide growth on ZrN is fast and sustainable, and the robust oxide features are promising candidates for multiscale (nanometre-to-micrometre) applications.

Body surface potential field representation fidelity: analysis of map estimation procedures.

The first part of this study analyzed the spatial-temporal error distribution of the Lux-type limited lead system. Quantitative new evidence is reported that the 32-lead anterior subset estimates the further 160 leads with an average amplitude error less than 38.5 microV. The spatial error distribution revealed 8 sites where the error is the highest, primarily on the anterior side, independent of the clinical classification. The second part of the study examined inter-lead-system conversion strategies for interpolating the Lux-192 lead maps from the Montreal-63 data. The methodology based on the Laplacian interpolation yielded an average amplitude error of 143.7 microV and an average correlation of 0.87 for pattern fidelity. In this specific case a modified linear interpolation surpassed the Laplacian method. A presented example illustrates that even in cases when the fidelity of the signal information is heavily compromised the diagnostic information may remain less influenced.

Comparison of responses of helical strips of artery from anesthetized and untreated rats.

A comparison was made of the responses of helical strips of rat ventral tail artery from rats killed by cervical dislocation and rats subjected to poly-drug anesthesia. Anesthetized rats were premedicated with meperidine and atropine. Anesthesia was induced with thiopental and maintained with N2O. The animals were paralyzed with pancuronium and ventilated for 1 h. A mixture of fentanyl and droperidol was administered during anesthesia. Responses of arterial strips from these rats to norepinephrine, 5-hydroxytryptamine, vasopressin, and transmural electrical stimulation were identical with those of similar strips from control rats. Poly-drug anesthesia does not alter responses of isolated strips subsequently studied in vitro.