Large Tertiary Referral Center Research Articles

Clinical Features and Induction Outcome of Adult Patients with Acute Lymphoblastic Leukemia: Findings from a Large Tertiary Care Referral Center in Palestine

Clinical Features and Induction Outcome of Adult Patients with Acute Lymphoblastic Leukemia: Findings from a Large Tertiary Care Referral Center in Palestine

The relationship between computed tomography-derived body composition, systemic inflammation, and survival in patients with abdominal aortic aneurysm

ObjectivePatient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair or by endovascular aneurysm repair, remain challenging. Computed tomography (CT)-derived body composition analysis (CT-BC) and systemic inflammation-based scoring systems such as the systemic inflammatory grade (SIG) appear to offer prognostic value in patients with AAA undergoing endovascular aneurysm repair. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in noncancer populations are lacking. The present study aimed to examine the relationship between CT-BC, SIG, and survival in patients undergoing elective intervention for AAA. MethodsA total of 611 consecutive patients who underwent elective intervention for AAA at three large tertiary referral centers were retrospectively recruited for inclusion into the study. CT-BC was performed and analyzed using the CT-derived sarcopenia score (CT-SS). Subcutaneous and visceral fat indices were also recorded. SIG was calculated from preoperative blood tests. The outcomes of interest were overall and 5-year mortality. ResultsMedian (interquartile range) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) open surgical repair cases, 558 (91%) patients were male, and the median (interquartile range) age was 73.0 (11.0) years. Age (hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.28-2.14, P < .001), elevated CT-SS (HR: 1.58, 95% CI: 1.28-1.94, P < .001), and elevated SIG (HR: 1.29, 95% CI: 1.07-1.55, P < .01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 and SIG 0 subgroup was 92.6 (84.8-100.4) months compared with 44.9 (30.6-59.2) months in the CT-SS 2 and SIG ≥2 subgroup (P < .001). Patients with CT-SS 0 and SIG 0 had 90% (standard error: 4%) 5-year survival compared with 34% (standard error: 9%) in patients with CT-SS 2 and SIG ≥2 (P < .001). ConclusionsCombining measures of radiological sarcopenia and the systemic inflammatory response offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies.

Defining shoulder function and dysplasia in patients with longitudinal deficiencies of the upper limb

Phenotypic differences and functional limitations in children with congenital radial and ulnar longitudinal deficiencies (RLD/ULD) are well understood for the forearm and hand. However, anatomical features of shoulder elements in these pathologies have only been scarcely reported. Moreover, shoulder function has not been assessed in this patient population. Therefore, we aimed to define radiologic features and shoulder function of these patients at a large tertiary referral center. We prospectively enrolled all patients with RLD and ULD (minimum age: 7 years) for this study. Eighteen patients (12 RLD, 6 ULD) with a mean age of 17.9 years (range, 8.5-32.5) were evaluated using clinical examination (shoulder motion and stability), patient-reported outcome measures (Visual Analogue Scale [VAS], Pediatric/Adolescent Shoulder Survey [PASS], Pediatric Outcomes Data Collection Instrument [PODCI]), and radiologic grading of shoulder dysplasia (including length and width discrepancy of the humerus, glenoid dysplasia in the anteroposterior and axial view [Waters classification], and scapular and acromioclavicular dysplasia assessment). Descriptive statistics and Spearman correlation analyses were performed. Despite five (28%) cases having anterioposterior shoulder instability and five (28%) cases with decreased motion, outcome scores indicated an overall excellent function of the shoulder girdle, with mean VAS of 0.3 (range, 0-5), mean PASS of 97 (range, 75-100), and mean PODCI Global Functioning Scale of 93 (range, 76-100). The humerus was, on average, 15 mm shorter (range, 0-75), and metaphyseal and diaphyseal diameters both reached 94% of the contralateral side. Glenoid dysplasia was detected in nine (50%) cases, with increased retroversion evident in 10 (56%) cases. However, scapular (n=2) and acromioclavicular (n=1) dysplasia were rare. Based on radiographic findings, a radiologic classification system for dysplasia types IA, IB, and II was developed. Adolescent and adult patients with longitudinal deficiencies exhibit various mild-to-severe radiologic abnormalities around the shoulder girdle. Nevertheless, these findings did not seem to negatively affect shoulder function as the overall outcome scores were excellent.

Prognostic significance of size and function of the subpulmonary left ventricle in patients with a systemic right ventricle

Abstract Funding Acknowledgements Type of funding sources: None. Background Systolic dysfunction of the systemic right ventricle (SRV) is a well-recognized predictor of adverse events in adults with transposition of great arteries (TGA) after atrial switch repair or with congenitally corrected TGA (ccTGA). The prognostic role of subpulmonary left ventricle (LV), however, remains unclear. Purpose To assess the prognostic significance of echocardiographic parameters of subpulmonary LV size and systolic function. Methods All adult patients with the SRV who underwent transthoracic echocardiography in 2010–2018 at a large tertiary referral centre were identified from a digitally recorded echocardiographic database. Biventricular size and function were assessed at the most recent exam. The study endpoint was all-cause mortality and heart or heart-lung transplantation. Results We included 180 patients, 100(55.6%) male, mean age 42.4±12.3 years, of whom 103(57.2%) had undergone Mustard/Senning operations and 77(42.8%) had ccTGA. One half of patients were in NYHA class ≥2 and 113 (63.5%) were receiving heart failure medication(s). During a follow-up period of 4.9[3.8–5.7] years, 28(15.6%) patients died and 4(2.2%) underwent heart or heart-lung transplantation. Univariable predictors of death or transplantation included older age, NYHA class III/IV, history of atrial arrhythmias, presence of pacemaker or cardioverter-defibrillator, high BNP, and echocardiographic markers of both SRV and subpulmonary LV size and function (Figure 1). On multivariable Cox analysis, indexed LV end-systolic diameter (ESDi; HR 2.77 [95%CI 1.35–5.68], p = 0.01), LV fractional area change (FAC; HR 0.7 [95%CI 0.57–0.85], p = 0.002), SRV basal diameter (HR 1.66 [95%CI 1.21–2.29], p = 0.005), and SRV FAC (HR 0.65 [95%CI 0.49–0.87], p = 0.008) remained predictive of mortality or transplantation. On ROC analysis, subpulmonary LV parameters performed better than SRV markers in predicting death or transplantation (Figure 2). Conclusions A raised LV ESDi and reduced LV FAC were strongly associated with mortality and heart or heart-lung transplantation independent of SRV size and function. Accurate echocardiographic assessment of the subpulmonary LV is therefore essential for risk stratification and management of patients with the SRV and should be a part of routine echocardiographic protocols.

Post-treatment 18F-fludeoxyglocuse-positron emission tomography in human papillomavirus-associated oropharyngeal cancer.

Human papillomavirus association has changed the landscape of treatment for oropharyngeal squamous cell carcinoma; it remains to be seen whether current post-treatment surveillance schedules are effective. Evaluate whether post-treatment surveillance of oropharyngeal cancer through FDG-PET imaging is modified by human papillomavirus association. A prospective cohort analysis of retrospective data was conducted for patients undergoing treatment of oropharyngeal cancer between 2016 and 2018. This study was conducted at a single large tertiary referral center in Brisbane, Australia. Two-hundred and twenty-four patients were recruited for the purposes of the study, 193 (86%) with HPV-associated disease. In this cohort FDG-PET had a sensitivity of 48.3%, specificity of 72.6%, positive predictive value of 23.7%, and negative predictive value of 88.8% in detecting disease recurrence. FDG-PET in HPV-associated oropharyngeal cancer has significantly lower positive predictive value when compared to non-HPV-associated oropharyngeal cancer. Caution should be used when interpreting positive post-treatment FDG-PET.

Role of immune checkpoint inhibitors in metastatic uveal melanoma: a single-center retrospective cohort study

Background Uveal melanoma is an orphan malignancy with very limited data on treatment options in metastatic setting. Methods In this single-center retrospective study, we describe real-world epidemiological and survival data on 121 metastatic uveal melanoma (MUM) patients registered in our institution. As a large tertiary referral center, almost 30% of all diagnoses in the Flemish region of Belgium were covered. Primarily, we determined whether introduction of immune checkpoint inhibitors (ICI) led to improved overall survival (OS) in MUM patients. Secondarily, response rates to ICI were assessed and we evaluated whether first-line ICI could be a valid alternative to liver-directed therapy (LDT) in liver-only disease. Results The initially perceived 10.8 months survival benefit from treatment with ICI disappeared after correction for immortality bias. By analyzing treatment type as time-varying covariate on OS, no significant benefit of ICI over other systemic therapies (HR = 0.771) or best supportive care (BSC) (HR = 0.780) was found. Also comparison of the pre-ICI versus ICI era showed no OS improvement after introduction of ICI in our center (p = 0.7994). Only liver-directed and local oligometastatic approaches were associated with a lower chance of mortality when compared to ICI (p = 0.0025), other systemic therapies (p = 0.0001) and BSC (p = 0.0003), yet without correction for selection bias. We reported overall response rates on ICI ranging from 8–15% and we found some support for neoadjuvant strategies with ICI resulting in remission or downsizing, allowing oligometastatic approaches later on. In first-line liver-only disease, median real-world progression-free survival and OS did not significantly differ between patients treated with LDT or ICI upfront (p = 0.2930 and p = 0.5461 respectively). Conclusion Although we documented responses to ICI, our analyses do not demonstrate an OS benefit of ICI over alternative treatment strategies for MUM. However, local treatment options, whether liver-directed or for oligometastatic disease, may be beneficial and should be considered.

Chronic Kidney Disease Predicts Greater 5-Year Mortality Following Major Limb Amputation.

Severe chronic kidney disease (CKD) predicts greater mortality after major lower extremity amputation (MLEA), but it remains poorly understood whether this finding extends to patients with earlier stages of CKD. We assessed outcomes for patients with CKD in a retrospective chart review of all patients who underwent MLEA at a large tertiary referral center from 2015 to 2021. We stratified 398 patients by glomerular filtration rate (GFR) and conducted Chi-Square and survival analysis. Preoperative CKD diagnosis was associated with many comorbidities, less 1-year follow-up, and greater 1- and 5-year mortality. Kaplan-Meier analysis showed worse 5-year survival for patients with any stage of CKD (62%) compared to patients without CKD (81%; P < .001). Greater 5-year mortality was independently predicted by moderate CKD (hazard ratio (HR) 2.37, P = .02) as well as severe CKD (HR 2.09, P = .005). These findings demonstrate the importance of identifying and treating CKD early preoperatively.

Corneal Culture and Antibiotic Susceptibility Results for Microbial Keratitis in the Mid-Atlantic Region of the United States, 2016 to 2020.

To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States. Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020. Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; ∼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin. Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.

Accuracy between clinical and radiological diagnoses compared to surgical orbital biopsies.

To assess the concordance between diagnosing orbital lesions by clinical examination, orbital imaging, and histological evaluation, in order to help guide future research and clinical practice. A retrospective analysis was undertaken at a large regional tertiary referral centre of all surgical orbital biopsies performed over a 5-year period, from 1st January 2015 until 31st December 2019. Accuracy and concordance between clinical, radiological and histological diagnoses are reported as percentage sensitivity and positive predictive value. A total of 128 operations involving 111 patients were identified. Overall, sensitivities of 47.7% for clinical and 37.3% for radiological diagnoses were found when compared to the histological gold standard. Vascular lesions that have characteristic clinical and radiological features had the highest sensitivity at 71.4% and 57.1%, respectively. Inflammatory conditions showed the lowest sensitivity in both clinical (30.3%) and radiological (18.2%) diagnoses. The PPV for inflammatory conditions were 47.6% for clinical and 30.0% for radiological diagnoses. Accurate diagnoses are difficult to reach by relying on clinical examination and imaging alone. Surgical orbital biopsy with histological diagnosis should remain the gold standard approach for definitively identifying orbital lesions. Although larger scale prospective studies would help further refine concordance and guide future research avenues.

Intracoronary Brachytherapy for Restenosis: 20 Years of Follow-Up

Background/purposeIntracoronary brachytherapy (ICB) has mainly been used to treat in-stent restenosis following percutaneous coronary intervention and was virtually abandoned about 20 years ago. However, patients treated with this strategy are still alive and some teams continue to perform this therapy. We aimed to investigate the very long-term clinical outcome of patients treated with ICB. Methods/materialsA total of 173 consecutive patients who had been treated with ICB at a large tertiary referral centre between 1998 and 2003 were included. The primary endpoint of the study was all-cause mortality. The secondary endpoints were as follows: occurrence of major adverse cardiac events (MACE, defined as all-cause death, non-fatal myocardial infarction, or target vessel revascularization), cardiac death, and presence of angina at the end of follow-up. ResultsPatients' mean age at the time of ICB was 64 ± 10 years and 77 % were male. Restenosis (bare metal stent vs. balloon angioplasty) was the only indication for ICB. Unstable angina was present in 34 % of the patients. Follow-up was available for 166 patients. After a mean follow-up of 20 ± 1.3 years, 66 % of the patients had died (including 74 patients (67 %) with cardiac death). Cumulative MACE rate at 20 years was 96 %. ConclusionsVery long-term follow-up of patients with in-stent restenosis treated with ICB confirmed a high all-cause mortality rate mainly due to cardiac causes and MACEs.

Trends in Modifiable Risk Factors Amongst First Presentation ST Elevation Myocardial Infarction Patients in a Large Longitudinal Registry.

Recent studies suggest that the risk factor profile of patients presenting with ST elevation myocardial infarction (STEMI) is changing. The aim is to determine if there has been a shift of cardiovascular risk factors to cardiometabolic causes in the first presentation STEMI population. We analysed data from a STEMI registry from a large tertiary referral percutaneous coronary intervention centre to determine the prevalence and trends of the modifiable risk factors of hypertension, diabetes, smoking and hypercholesterolaemia. Consecutive first presentation STEMI patients between January 2006 to December2018. Among the 2,366 patients included (mean age 59, SD 12.66, 80% male) the common risk factors were hypertension (47%), hypercholesterolaemia (47%) current smoking (42%) and diabetes (27%). Over the 13 years, patients with diabetes (20% to 26%, OR 1.09 per year, CI 1.06-1.11, p<0.001) and patients with no modifiable risk factors increased (9% to 17%, OR 1.08, CI 1.04-1.11, p<0.001). Concurrently there was a fall in prevalence of hypercholesterolaemia, (47% to 37%, OR 0.94 per year, CI 0.92-0.96, p<0.001) and smoking (44% to 41%, OR 0.94, CI 0.92-0.96, p<0.001) but no significant change in rates of hypertension (53% to 49%, OR 0.99, CI 0.97-1.01, p=0.25). The risk factor profile of first presentation STEMI has changed over time with a reduction in smoking and a concurrent rise in patients with no traditional risk factors. This suggests the mechanism of STEMI may be changing and further investigation of potential causal factors is warranted for the prevention and management of cardiovascular disease.

Doctors' knowledge and perceptions of perioperative nutrition support; results from a large Australian tertiary referral Centre.

Nutritional optimisation in the perioperative period is essential in the prevention and treatment of malnutrition, a state of poor bodily function caused by a lack of nutritional intake, thereby altering body composition.1 Although identification and treatment of malnutrition is well recognized as a key component of Enhanced Recovery After Surgery (ERAS) guidelines, it is still highly prevalent, and significantly associated with poor outcomes. Studies have shown that up to 50% of patients undergoing abdominal surgery are malnourished.2-5 These patients are further at risk due to reduced recognition, combined with poor clinician understanding of treatment strategies due to their lack of knowledge and experience.6-10 To identify how we can improve on surgical nutrition management within our surgical units, we performed a survey within a large tertiary referral hospital in Melbourne, Australia. The project was approved by the Western Health Office of Research (QA2020.13_61439). A purpose-built, 23-item anonymous online REDCap survey was distributed to all doctors (including interns, residents, registrars, fellows and consultants) working across all general surgical units at Western Health. As our recruitment strategy involved advertising the survey at the weekly surgical morbidity and mortality meeting and via email distribution, response rate calculation was not feasible. The survey, developed by a team of senior academic dietitians and surgeons, included Likert scale ‘agree/disagree’ questions as well as clinical multiple-choice questions to assess doctor's perceptions and knowledge of perioperative nutritional support within general surgery. Of the 50 respondents, the majority were junior doctors (11 [22%] interns and 17 [34%] residents), 11 were registrars (22%) and a further 11 were consultant surgeons (22%). Only 24% (12) of respondents reported any prior training on perioperative nutritional support. While all respondents agreed on the importance of perioperative nutrition training (100%) and 94% (47) agreed on the need for nutritional assessment both before and after abdominal surgery, only 46% (23) felt confident in being able to initiate enteral or parenteral support according to evidence based guidelines. This was reflected when only approximately half of respondents correctly identified the correct timing to commence enteral (62%; 31) and total parenteral nutrition (50%; 25). Early identification of patients with nutritional deficits is important to ensure appropriate and timely interventions, however only a small proportion (20%; 10) of doctors surveyed were confident in identifying malnutrition and only 34% (17) were able to identify the common risks of malnutrition in a surgical patient. Only 38% (19) of doctors understood that the commonly used ‘fast from midnight’ order was unnecessary.11 These findings correspond with the nutritional knowledge gaps that have been observed across the world amongst medical students, junior medical staff and surgeons.6-10 Many hospitalized patients suffer from malnutrition, and those undergoing abdominal surgery, especially emergency cases, are at risk of deterioration owing to prolonged fasting and slow return to adequate nutritional intake. A recent British audit showed that patients undergoing emergency surgery are more likely to fast for longer periods of time (more than 12 h for clear fluids, and 24 h for food) compared with elective patients.11 Whilst we have shown the majority of doctors understand the importance of nutrition optimisation, they may not be equipped with the knowledge of when and how to do so. The implementation of ERAS protocols which include nutrition components can help standardize nutrition supplementation.12 A recent study also showed a lack of nutrition related education in British postgraduate training curriculums, suggesting a potential solution of implementing nutritional based objectives in all postgraduate training programs.7, 13 We recommend that doctors should be encouraged to make use of available hospital resources, in particular involvement of dietitians and the multidisciplinary team to help with early identification of patients at risk of malnutrition. Embedded education in both undergraduate and postgraduate training could help improve on doctors understanding and management of nutritional deficiencies. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Howard H. Y. Tang: Formal analysis; writing – original draft; writing – review and editing. Danielle Taylor: Data curation; investigation; methodology; writing – review and editing. Irene Deftereos: Conceptualization; methodology; writing – review and editing. Aurora Ottaway: Methodology; writing – review and editing. Justin M. C. Yeung: Conceptualization; supervision; visualization; writing – review and editing.

Patients’ understanding of long-term cardiovascular risks and associated health-seeking behaviours after pre-eclampsia

ObjectiveThe lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to...

Clinical characteristics and management of coexistent cardiomyopathy in patients with bicuspid aortic valve.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. However, the prevalence, clinical characteristics, and current management of BAV associated with inherited cardiomyopathy, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular noncompaction (LVNC) have not been well described. Consecutive patients diagnosed with BAV at a large tertiary cardiovascular referral center between 2009 and 2018 were retrospectively assessed for HCM, DCM, and LVNC based on clinical and echocardiographic criteria. Patients with coexistent conditions were investigated further. Of 3533 patients with BAV screened, 57 (1.6%) had concomitant cardiomyopathy. BAV was combined with HCM in 30 of these patients, with DCM in 19, and with LVNC in eight. Forty-six patients (80.7%) were male, and the mean age at first diagnosis was 47 years for BAV with HCM, 49 years for BAV with DCM, and 35 years for BAV with LVNC. Heart failure and aortic valve dysfunction were common in these patients, and the prevalence of coexisting aortopathy was 43.3%, 26.3% and 25.0%, respectively, for BAV with HCM, DCM and LVNC. During the index hospitalization, 24 of the 57 patients (42.1%) underwent surgery, 16 (28%) underwent aortic valve and/or aortic surgery, and 16 of the 30 patients with HCM had a Morrow procedure. There were no deaths or other major adverse cardiovascular events. The prevalence of inherited cardiomyopathy was higher in our patients with BAV than in the general population. Aortopathy and heart failure were common, with almost half of patients requiring surgery at diagnosis.

A Clinical Decision Tool to Calculate Pretest Probability of Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.

Efficacy and safety of double- versus single-balloon retrograde enteroscopy.

Data on the safety and efficacy of double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are conflicting. We aimed to compare the efficacy and safety of retrograde DBE to SBE. We performed a retrospective analysis of all patients who underwent retrograde DBE or SBE at a large tertiary referral center from 2008 to December 2018. Outcomes assessed included technical success, diagnostic yield, therapeutics, depth of insertion, and procedural duration. A total of 523 (403 DBE, 120 SBE) patients underwent retrograde enteroscopy during the study period. The mean age was 59.4 ± 17.24 and 59.57 ± 16.94 years in DBE and SBE groups, respectively. There was no difference in technical success (91.0% vs. 92.5%, P = 0.85), diagnostic yield (40.9% vs. 40.8%, P = 0.95), and therapeutics (17.1% vs. 19.1%, P = 0.61) between DBE and SBE. Compared to SBE, DBE had significantly shorter mean procedure time (26.5 ± 34.5 min vs. 34.8 ± 29.4 min, P = 0.01) and higher maximal depth of insertion from ileocecal valve (108.1 ± 84.1 cm vs. 73.3 ± 63.4 cm, P = 0.001). Safety events were rare and similar in both groups. Retrograde DBE is associated with a significantly higher depth of insertion and shorter procedural duration, but similar diagnostic yield and technical success compared to SBE.

Tracheostomy insertion in COVID-19: insertion practice and factors leading to unplanned tube exchange.

Tracheostomy insertion in patients with coronavirus disease 2019 (COVID-19) presents unique challenges. Patients frequently have high ventilatory requirements, and as an aerosol generating procedure, tracheostomy insertion creates the potential for staff transmission. Problems with tracheostomies contribute to morbidity and mortality, and tracheostomy changes may increase risks of staff transmission. We sought to quantify the incidence of clinically necessitated tracheostomy changes, establish the indications for change and investigate the incidence of staff transmission. We conducted a single institution, retrospective, observational cohort study of all intensive care unit (ICU) patients with COVID-19 who had a tracheostomy between March 2020 and April 2021. The institution is a large tertiary referral centre in Ireland. Forty-three patients had a tracheostomy during the study period. All were a Shiley™ Flexible Adult Taperguard or Shiley™ XLT Tracheostomy. 14 patients (33%) required a tracheostomy change, with the majority (57%) involving a change from a standard size to an extended length tracheostomy. Persistent leak was the most common indication for change (71.6%). Other indications included patient-ventilator dyssynchrony, persistent cough and accidental decannulation. No staff transmission of COVID-19 occurred during this study. The incidence of tracheostomy change was 33%, highlighting the importance of selecting the right tracheostomy for each patient. We discuss how key characteristics of tracheostomies such as type, size, length and inner diameter may impact flow, resistance and work of breathing, leading to unplanned tracheostomy change. No staff transmission occurred arising from tracheostomy insertion, adding to increasing evidence that tracheostomy insertion in COVID-19 appears safe with adherence to guidelines describing the correct use of personal protective equipment.

P756 Cumulative adverse events of anti-TNF therapy in IBD patients at a large tertiary centre – a 13-year real-world experience

Abstract Background Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. The aim of the study was to record cumulative AEs in IBD patients and report on real-world safety profile of this class of drugs. Methods All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary referral centre between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. Data on malignancies in this cohort was collected separately. The data were analysed and statistical analysis carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0. Results Total of 844 patients (M=408, 48%; median age 37years) were included, of which 61% were Caucasian. Majority had CD (608;72%) with mean age at diagnosis of 27y (SD 15y) and a median disease duration of 12years. About 50% of patients were on monotherapy and adalimumab was most frequently used (52%). A significant proportion of patients (44%) discontinued therapy during the follow-up period covered by the study (median duration 5years); infliximab showed best persistence rate (Fig 1). The commonest AEs were dermatological followed by auto-immune. Infections affected all age groups and bacterial infections were most common. Male sex, age groups of 18-50 years were statistically more likely to develop an AE (Table 1). 16 malignancies and 1 death were recorded in this cohort. Conclusion In our cohort, a significant number of AEs to anti-TNFs were noted, frequently resulting in the withdrawal of therapy. Although effective, anti-TNFs related AEs lead to poor persistence rates and contribute to increased risk of infections, particularly in &amp;gt;60y age group. Clinicians must be aware of the wide range of AEs due to anti-TNFs; these risks must be considered, and patients selected carefully to maximize success. With a wider choice of biologics and small molecules currently available, other options with apparently more favourable safety profiles could be considered earlier in the treatment algorithm.

P475 Infections and malignancies during anti-TNF therapy in IBD patients affect all age groups – results from a 13-yr real-world retrospective study

Abstract Background Anti-TNFα is the first class of biologics approved for treatment of moderate-to-severely active Inflammatory Bowel Disease (IBD). More than two decades on, anti-TNFs remain one of the most commonly used biologics for both Ulcerative Colitis (UC) and Crohn’s Disease (CD), and often as first-line therapy. Although effective, they cause several adverse events (AEs), sometimes requiring withdrawal of therapy. We aimed to report on AEs with a focus on risk of infections and malignancies in this large cohort. Methods All IBD patients exposed to anti-TNF therapy were identified from EMR at two centres of a large tertiary referral centre between January 2009 and June 2022. All relevant demographic and clinical data were collected for those patients with well recorded AEs and follow-up. Data on cumulative AEs directly attributed to anti-TNFs that ranged from mild reactions to serious AEs (defined as those requiring review/withdrawal of anti-TNF), were collected. The data were analysed and statistical analysis carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0. Results Total of 844 patients (M=408, 48%; median age 37years) were included, of which 61% were Caucasian. Majority had CD (608;72%) with mean age at diagnosis of 27y (SD 15y) and a median disease duration of 12years. About 50% of patients were on monotherapy and adalimumab was most frequently used (52%).There were 392 cumulative AEs recorded in this cohort with 78 infections (20% of all AEs). Among these, majority were bacterial infections, followed by Clostridium difficile. Tuberculosis(TB) was diagnosed in 5 patients. Infections were distributed evenly across all age groups with no significant difference between monotherapy or combination therapy. Majority of infections responded to anti-microbials and patients were able to resume anti-TNFs without major complications. One death recorded due to viral hepatitis. Detailed breakdown is given in Table 1. Malignancies were recorded in 16 (2%) patients and 6 were on combination therapy. Skin cancers were most common and there were no lymphomas noted. The details of malignancy are given in Table 1. Conclusion In this large cohort, infections were one of the commonest AEs recorded during exposure to anti-TNF therapy.Bacterial infections were most frequent across all age groups requiring pause of anti-TNF in most cases and withdrawal in very few. Opportunistic infections were few and reported TB cases was as low as 0.5% of total cohort. Skin cancer was the most common malignancy and no lymphomas were reported in this cohort. Clinicians need to be aware of these risks in younger patients as anti-TNFs result in infections and malignancies across all age groups and not particularly limited to the elderly.

28-Year Experience with Ruptured and Symptomatic Type I-III Thoracoabdominal Aortic Aneurysms at a Large Tertiary Referral Center

Given the relative rarity of ruptured and symptomatic type I-III thoracoabdominal aortic aneurysms (TAAA), data is scarce with regard the outcomes of those who survive to repair. The goal of this study was to determine short and long-term outcomes after open repair of type I-III TAAA surgery for ruptured and symptomatic TAAA and compare the results to elective TAAA repairs. All open type I-III TAAA repairs performed from 1987 to 2015 were evaluated using an institutional database. Charts were retrospectively evaluated for perioperative outcomes: major adverse event (MAE), in-hospital death, spinal cord ischemia (SCI) and long-term survival. Ruptured, symptomatic and elective repair cohorts were created for comparison. Univariate analysis was performed using the Fisher's exact test for categorical variables and analysis of variance (ANOVA) for continuous variables. Logistic regression was used for in-hospital endpoints; survival analysis was performed with Cox proportional hazards modelling and Kaplan-Meier techniques. Five hundred-sixteen patients had an open type I-III TAAA repair during the study period. Fifty-nine (11.4%) were performed for rupture and 51 (9.9%) were performed for symptomatic aneurysms (RAs). Ruptured and symptomatic groups were more likely to be older, female, and have larger presenting aortic diameters. Most of the ruptured and symptomatic cases were transferred from an outside facility (59.3% and 54.9%, respectively). Intraoperatively, the elective cohort was more likely to receive left heart bypass as an operative adjunct; ruptures were less likely to receive a renal bypass, and operative time was highest for the elective cohort. Perioperative mortality was 18.6% for ruptured, 2.0% for symptomatic, and 7.4% for elective indications. Ruptures were most likely to require new hemodialysis after repair (20.3% vs. 10.3% for elective, P=0.02). On adjusted analysis, ruptures were more likely to suffer from perioperative death (adjusted odds ratio [AOR]: 4.5, 95% confidence interval (CI): 1.7-11.4) and MAEs (AOR: 2.8, 95% CI: 1.4-5.4). Ruptured and symptomatic aneurysms were not independently associated with SCI; however, preoperative hemodynamic instability was predictive (AOR: 8.7, 95% CI: 1.7-44.2). Both rupture and symptomatic cases were associated with decreased survival on Kaplan-Meier analysis with 5-year survival for ruptures at 35%, symptomatic at 47.7% and elective at 63.7%, P<0.001. Adjusted hazards of death were 1.2 (95% CI: 0.9-1.8) in the symptomatic cohort and 2.3 (95% CI: 1.5-3.7) in the ruptured cohort. Open ruptured and symptomatic type I-III TAAA repairs can be performed with acceptable morbidity and mortality. Most symptomatic and rupture repairs were performed after transfer from another institution. Postoperative SCI is most strongly related to the preoperative hemodynamic status of the patient.