Engagement with a youth violence intervention programme is associated with lower re-attendance after violent injury: A UK major trauma network observational study.

The hospital based Redthread Youth Violence Intervention Programme (YVIP) utilises experienced youth workers to support 11-24 year olds following an episode of violent injury, assault or exploitation who present to the Emergency Department (ED) at the East Midlands Major Trauma Centre (MTC), Nottingham, UK. The YVIP aims to promote personal change with the aim of reducing the incidence of further similar events. We conducted a retrospective, observational, cohort study to examine the association between engagement with the YVIP and re-attendance rates to the ED following a referral to Redthread. We also examined factors associated with engagement with the full YVIP. We found that 573 eligible individuals were referred to the YVIP over two years. Assault with body parts 34.9% (n = 200) or a bladed object 29.8% (n = 171) were the commonest reason for referral. A prior event rate ratio (PERR) analysis was used to compare rates of attendance between those who did and did not engage with the full YVIP. Engagement was associated with a reduction in re-attendances of 51% compared to those who did not engage (PERR 0.49 [95% 0.28-0.64]). A previous attendance to the ED by an individual positively predicted engagement. (OR 2.82 [95% CI 1.07-7.42], P = 0.035). A weekend attendance (OR 0.26 [0.15-0.44], P<0.001) and a phone call approach (OR 0.25 [0.14-0.47], P = 0.001), rather than a face-to-face approach by a Redthread worker, negatively impacted engagement. In conclusion, assaults with or without a weapon contributed to a significant proportion of attendances among this age group. The Redthread YVIP was associated with reduced rates of re-attendance to the East Midlands MTC among young persons who engaged with the full programme.

The ICaRAS randomised controlled trial: Intravenous iron to treat anaemia in people with advanced cancer - feasibility of recruitment, intervention and delivery.

BACKGROUND: Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. AIMS: To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. DESIGN: A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). SETTING/PARTICIPANTS: People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. RESULTS: 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. CONCLUSION: The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.

Patterns and mechanisms of major trauma injuries during and after the UK Covid-19 Nationwide lockdown: analysis from a UK Major Trauma Centre.

PURPOSE: To compare patterns and mechanisms of injuries during and after the UK Nationwide lockdown during the COVID-19 pandemic. METHODS: This prospective cohort study included all major trauma admissions during the 10-week period of the nationwide lockdown (09/03/2020-18/05/2020), compared with admissions in the 10-weeks following the full lifting of lockdown restrictions (04/07/20-12/09/2020). Differences in the volume, spectrum and mechanism of injuries presenting during and post-lockdown were compared using Fisher's exact and Chi-squared tests as appropriate. The associated risk of 30-day mortality was examined using univariable and multivariable logistic regression. RESULTS: A total of 692 major trauma admissions were included in this analysis. Of these, 237 patients were admitted during the lockdown and 455 patients were admitted post-lockdown. This represented a twofold increase in trauma admission between the two periods. Characteristically, both cohorts had a higher proportion of male patients (73.84% male during lockdown and 72.5% male post-lockdown). There was a noted shift in age groups between both cohorts with an overall more elderly population during lockdown (p = 0.0292), There was a significant difference in mechanisms of injury between the two cohorts. The 3-commonest mechanisms during the lockdown period were: Road traffic accidents (RTA)-31.22%, Falls of less than 2 m-26.58%, and falls greater than 2 m causing 22.78% of major trauma admissions. However, in the post-lockdown period RTAs represented 46.15% of all trauma admissions with falls greater than 2 m causing 17.80% and falls less than 2 m causing 15.16% of major trauma injuries. With falls in the elderly associated with an increased risk of mortality. In terms of absolute numbers, there was a twofold increase in major trauma injuries due to stabbings and shootings, rising from 25 admitted patients during the lockdown to 53 admitted patients post-lockdown. CONCLUSIONS: The lifting of lockdown restrictions resulted in a twofold increase in major trauma admissions that was also associated with significant changes in both the demographic and patterns of injuries with RTA's contributing almost half of all injury presentations. TRIAL REGISTRATION: This study was classed as a service evaluation and registered with the local audit department, registration number: 20-177C.

Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-analysis.

Importance: Intravenous iron is recommended by many clinical guidelines based largely on its effectiveness in reducing anemia. However, the association with important safety outcomes, such as infection, remains uncertain. Objective: To examine the risk of infection associated with intravenous iron compared with oral iron or no iron. Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials (RCTs) from 1966 to January 31, 2021. Ongoing trials were sought from ClinicalTrials.gov, CENTRAL, and the World Health Organization International Clinical Trials Search Registry Platform. Study Selection: Pairs of reviewers identified RCTs that compared intravenous iron with oral iron or no iron across all patient populations, excluding healthy volunteers. Nonrandomized studies published since January 1, 2007, were also included. A total of 312 full-text articles were assessed for eligibility. Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) and Cochrane recommendations, and the quality of evidence was assessed using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Two reviewers extracted data independently. A random-effects model was used to synthesize data from RCTs. A narrative synthesis was performed to characterize the reporting of infection. Main Outcomes and Measures: The primary outcome was risk of infection. Secondary outcomes included mortality, hospital length of stay, and changes in hemoglobin and red blood cell transfusion requirements. Measures of association were reported as risk ratios (RRs) or mean differences. Results: A total of 154 RCTs (32 920 participants) were included in the main analysis. Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I2 = 37%; moderate certainty of evidence). Intravenous iron also was associated with an increase in hemoglobin (mean difference, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL; I2 = 94%) and a reduction in the risk of requiring a red blood cell transfusion (RR, 0.93; 95% CI, 0.76-0.89; I2 = 15%) when compared with oral iron or no iron. There was no evidence of an effect on mortality or hospital length of stay. Conclusions and Relevance: In this large systematic review and meta-analysis, intravenous iron was associated with an increased risk of infection. Well-designed studies, using standardized definitions of infection, are required to understand the balance between this risk and the potential benefits.

Differences in the On- and Off-Tumor Microbiota between Right- and Left-Sided Colorectal Cancer.

This study aims to determine differences in the on- and off-tumor microbiota between patients with right- and left-sided colorectal cancer. Microbiome profiling of tumor and tumor-adjacent biopsies from patients with right-sided (n = 17) and left-sided (n = 7) colorectal adenocarcinoma was performed using 16S ribosomal RNA sequencing. Off-tumor alpha and beta diversity were significantly different between right- and left-sided colorectal cancer patients. However, no differences in on-tumor diversity were observed between tumor locations. Comparing the off-tumor microbiota showed the right colon to be enriched with species of the Lachnoclostridium, Selenomonas, and Ruminococcus genera. Whereas the left colon is enriched with Epsilonbacteraeota phylum, Campylobacteria class, and Pasteurellales and Campylobacterales orders, in contrast, the on-tumor microbiota showed relatively fewer differences in bacterial taxonomy between tumor sites, with left tumors being enriched with Methylophilaceae and Vadin BE97 families and Alloprevotella, Intestinibacter, Romboutsia, and Ruminococcus 2 genera. Patients with left-sided colorectal cancer had large taxonomic differences between their paired on- and off-tumor microbiota, while patients with right-sided colorectal cancer showed relatively fewer taxonomic differences. Collectively, this suggests that the right and left colon show distinctive bacterial populations; however, the presence of a colonic tumor leads to a more consistent microbiota between locations.

Rectal cancer: Watch-and-wait and continuing the rectal-preserving strategy with local excision for incomplete response or limited regrowth.

BACKGROUND: Deferral of conventional surgery for rectal cancer after neo-adjuvant chemo-radiotherapy is gaining increasing interest, particularly for patients who are too frail to undergo major surgery but also those who wish to avoid the adverse effects of major surgery. We elected to undertake a pragmatic approach to include all comers in a cohort with the aim of reflecting the clinical outcomes for patients on a deferral from conventional rectal surgery pathway, treated with neo-adjuvant chemo-radiation (CRT) with or without selective local excision (LE) offered to those who failed to demonstrate a complete clinical response (cCR). METHODS: Rectal cancer patients treated with neo-adjuvant CRT were stratified to a group of complete responders to CRT on a "watch and wait" (WW) pathway and a group who were treated with an additional local excision for persistent tumour. RESULTS: Regrowth was noted in 26% (11/42) in the WW group after 2 years surveillance, disease free survival was 94.5% (80-99%) at 1 year and 74.9% (44-76.4%) at 3 years. Recurrence was noted in 45% (10/22) in the CRT + LE group, disease free survival at 1 and 3 years was 74% (53.4-88.1) and 66.2% (45.6-82.4) respectively. CONCLUSION: A WW strategy for cCR is a viable pathway in the non-operative management of rectal cancer. We found the use of CRT + LE is a useful option for those who hope to avoid surgery but caution should be exercised due to substantially higher risk of recurrence.

Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients.

Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and ß-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.

The ICON Trauma Study: the impact of the COVID-19 lockdown on major trauma workload in the UK.

BACKGROUND: The global pandemic caused by SARS-CoV-2 has impacted population health and care delivery worldwide. As information emerges regarding the impact of "lockdown measures" and changes to clinical practice worldwide; there is no comparative information emerging from the United Kingdom with regard to major trauma. METHODS: This observational study from a UK Major Trauma Centre matched a cohort of patients admitted during a 10-week period of the SARS-CoV-2-pandemic (09/03/2020-18/05/2020) to a historical cohort of patients admitted during a similar time period in 2019 (11/03/2019-20/05/2019). Differences in demographics, Clinical Frailty Scale, SARS-CoV-2 status, mechanism of injury and injury severity were compared using Fisher's exact and Chi-squared tests. Univariable and multivariable logistic regression analyses examined the associated factors that predicted 30-days mortality. RESULTS: A total of 642 patients were included, with 405 in the 2019 and 237 in the 2020 cohorts, respectively. 4/237(1.69%) of patients in the 2020 cohort tested positive for SARS-CoV-2. There was a 41.5% decrease in the number of trauma admissions in 2020. This cohort was older (median 46 vs 40 years), had more comorbidities and were frail (p < 0.0015). There was a significant difference in mechanism of injury with a decrease in vehicle related trauma, but an increase in falls. There was a twofold increased risk of mortality in the 2020 cohort which in adjusted multivariable models, was explained by injury severity and frailty. A positive SARS-CoV-2 status was not significantly associated with increased mortality when adjusted for other variables. CONCLUSION: Patients admitted during the COVID-19 pandemic were older, frailer, more co-morbid and had an associated increased risk of mortality.

Temporal validation of metabolic nodal response of esophageal cancer to neoadjuvant chemotherapy as an independent predictor of unresectable disease, survival, and recurrence.

OBJECTIVES: We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using 18F-FDG PET-CT as new markers of disease progression, recurrence, and death. We aimed to validate our findings. METHODS: Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed. RESULTS: Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46-10.1; p = 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34-4.50); p = 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7-57.8) and 74.1% (56.6-86.3) respectively. CONCLUSIONS: This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy. KEY POINTS: • We previously described metabolic nodal response (mNR) of esophageal cancer to neoadjuvant chemotherapy using 18 F-FDG PET-CT as a predictor of unresectable disease, early recurrence, and death. • We report the first validation of these findings. In an immediately consecutive cohort, we found consistent proportions of patients with and without mNR, and associations with abandoned resection, early recurrence, and death. • This supports mNR as a new and actionable biomarker in esophageal cancer. Although external validation is required, mNR may provide surrogate information about the chemosensitivity of metastatic subclones, and the means to predict treatment success, guide personalized therapy, and follow-up.

Carbon Dioxide Embolism Associated With Transanal Total Mesorectal Excision Surgery: A Report From the International Registries.

BACKGROUND: Carbon dioxide embolus has been reported as a rare but clinically important risk associated with transanal total mesorectal excision surgery. To date, there exists limited data describing the incidence, risk factors, and management of carbon dioxide embolus in transanal total mesorectal excision. OBJECTIVE: This study aimed to obtain data from the transanal total mesorectal excision registries to identify trends and potential risk factors for carbon dioxide embolus specific to this surgical technique. DESIGN: Contributors to both the LOREC and OSTRiCh transanal total mesorectal excision registries were invited to report their incidence of carbon dioxide embolus. Case report forms were collected detailing the patient-specific and technical factors of each event. SETTINGS: The study was conducted at the collaborating centers from the international transanal total mesorectal excision registries. MAIN OUTCOME MEASURES: Characteristics and outcomes of patients with carbon dioxide embolus associated with transanal mesorectal excision were measured. RESULTS: Twenty-five cases were reported. The incidence of carbon dioxide embolus during transanal total mesorectal excision is estimated to be ≈0.4% (25/6375 cases). A fall in end tidal carbon dioxide was noted as the initial feature in 22 cases, with 13 (52%) developing signs of hemodynamic compromise. All of the events occurred in the transanal component of dissection, with mean (range) insufflation pressures of 15 mm Hg (12-20 mm Hg). Patients were predominantly (68%) in a Trendelenburg position, between 30° and 45°. Venous bleeding was reported in 20 cases at the time of carbon dioxide embolus, with periprostatic veins documented as the most common site (40%). After carbon dioxide embolus, 84% of cases were completed after hemodynamic stabilization. Two patients required cardiopulmonary resuscitation because of cardiovascular collapse. There were no deaths. LIMITATIONS: This is a retrospective study surveying reported outcomes by surgeons and anesthetists. CONCLUSIONS: Surgeons undertaking transanal total mesorectal excision must be aware of the possibility of carbon dioxide embolus and its potential risk factors, including venous bleeding (wrong plane surgery), high insufflation pressures, and patient positioning. Prompt recognition and management can limit the clinical impact of such events. See Video Abstract at http://links.lww.com/DCR/A961.

Risk of infection associated with intravenous iron preparations: protocol for updating a systematic review.

INTRODUCTION: The benefits and risk of intravenous iron have been documented in previous systematic reviews and continue to be the subject of randomised controlled trials (RCTs). An ongoing issue that continues to be raised is the relationship between administering iron and developing infection. This is supported by biological plausibility from animal models. We propose an update of a previously published systematic review and meta-analysis with the primary focus being infection. METHODS AND ANALYSIS: We will include RCTs and non-randomised studies (NRS) in this review update. We will search the relevant electronic databases. Two reviewers will independently extract data. Risk of bias for RCTs and NRS will be assessed using the relevant tools recommended by The Cochrane Collaboration. Data extracted from RCTs and NRS will be analysed and reported separately. Pooled data from RCTs will be analysed using a random effects model. We will also conduct subgroup analyses to identify any patient populations that may be at increased risk of developing infection. We will provide a narrative synthesis on the definitions, sources and responsible pathogens for infection in the included studies. Overall quality of evidence on the safety outcomes of mortality and infection will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This systematic review will only investigate published studies and therefore ethical approval is not required. The results will be broadly distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42018096023).

Role of nerve block as a diagnostic tool in pudendal nerve entrapment.

BACKGROUND: Pudendal nerve entrapment is a disabling condition which is difficult to diagnose and treat. Nantes criteria include the requirement of positive anaesthetic pudendal nerve block that is widely used to allow identification of patients likely to benefit from the definitive but invasive pudendal nerve release. This study aimed to determine if pudendal nerve blockade under general anaesthesia could diagnose and temporarily treat pudendal nerve entrapment in patients suffering from chronic pelvic/perineal pain and/or organ dysfunction. METHODS: This retrospective analysis of a prospectively maintained database examined the outcomes of all recipients of diagnostic pudendal nerve block in a quaternary referral centre between 2012 and 2017. Primary outcome was relief of perineal pain (transient or permanent). Secondary outcomes were demographics, referral patterns for definitive procedure and complication rates. Statistical analysis was performed using SPSS v 24. RESULTS: A total of 77 patients were included in the study. Mean age was 57.27 ± 13.55 years. Majority were females (n = 62, 80.5%). Relief of pain was experienced by 47 of 76 (68.1%) patients after initial injection. Complication rate of injection was 3.9% (n = 3) which in all cases was unilateral lower limb paraesthesia. Of the 37 patients (52.9%) referred, 20 underwent surgical decompression with 12 (60%) being successful. CONCLUSION: Pudendal nerve injection is a safe and simple procedure that can provide accurate diagnosis and transient relief from this chronic and debilitating problem. This technique helps to isolate patients suitable for pudendal nerve decompression which offers high success rates.