Prior History Research Articles

Documentation of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in the Allergy and Problem List of patients with a prior history of DRESS

Documentation of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in the Allergy and Problem List of patients with a prior history of DRESS

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. After up to 5years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Surgical and oncological results after rectal resections with or without previous treatment for prostate cancer.

Previous treatment for prostate cancer (PC) may potentially affect the surgical and oncological outcomes of subsequent rectal cancer surgery, but there are only a few studies regarding this particular group. In this study, we present the 3-year surgical and oncological results of rectal cancer patients who had received previous treatment for PC at a single Finnish tertiary referral centre. Data regarding all male patients diagnosed with rectal cancer and treated at Tampere University Hospital (TAUH) between 1997 and 2016 were gathered from medical records. In total, this study included 553 rectal cancer patients who underwent curative surgery, and 54 of them (9.8%) had a prior history of treatment for prostate cancer. Patients in the PC group were older and had more comorbidities compared with those in the non-PC group. The PC patients had a significantly higher risk of permanent stoma compared with the non-PC patients (61.5% vs. 45.2%, respectively, p = 0.025). The PC patients seemed to have lower tumours than the non-PC patients (87% vs. 75%, respectively, p = 0.05). Overall, the 3-year overall survival (OS) for the PC and non-PC patients was 74.1% and 80.6%, respectively. No significant differences were observed between the study groups even in the age-adjusted comparison [hazard ratio (HR): 1.07, confidence interval (CI) 95%: 0.60-1.89]. In the univariable analysis, radically operated patients without a history of PC exhibited an improved overall survival, (HR: 2.46, 95% CI: 1.34-4.53, p = 0.004). However, only a higher age-adjusted Charlson comorbidity index (CCI) and a low tumour location (<10 cm) were found to have an independent prognostic impact on worse OS in the multivariable analysis (HR: 1.57, 95% CI: 1.36-1.82, p < 0.001 and HR: 2.74, 95% CI: 1.32-5.70, p = 0.007, respectively). No significant differences were observed between the groups in terms of disease-free or local recurrence-free survival. Rectal cancer is more frequently found in the middle or lower part of the rectum in patients who have previously received treatment for prostate cancer. These patients also have a higher likelihood of requiring a permanent stoma. In radically operated rectal cancer, the PC group had a worse OS rate, according to the univariable analysis. However, the only independent prognostic factors for a worse OS that were highlighted in the multivariable analysis included a higher CCI and a low tumour location.

Abstract WP282: Association of Very Short Interval Blood Pressure Variability With Stroke

Background: While blood pressure variability (BPV) is associated with poor cardiovascular outcomes, the relationship between BPV obtained in a very short interval and stroke is unknown. We aim to examine the association between very short interval BPV and a history of stroke. Hypothesis: Higher BPV is associated with the likelihood of having a stroke. Methods: A cross-sectional study using 2017-2020 NHANES included 3 consecutive BP measurements taken 60 seconds apart. The average real variability (ARV) of systolic and diastolic BP (AVR-SBP and AVR-DBP) was assessed as an average of absolute difference in consecutive BP. The association of AVR-SBP and AVR-DBP and the history of stroke was examined by multiple logistic regression. Results: Of 9,693 adult participants, mean±SD age was 50±19 years and 51% were female. Up to 5% (487 patients) had a history of stroke. Mean of the three average SBP and DBP were 120±20 and 72±12 mmHg, respectively. Median (IQR) of ARV-SBP was 3.5 (2, 6) mmHg and of ARV-DBP was 2.4 (1.5, 4) mmHg. Patients with stroke had significantly higher SBP and ARV-SBP, but not DBP and ARV-DBP compared to non-stroke patients (mean difference (95%CI) of SBP 11 (9, 13); ARV-SBP 0.7, (0.4, 1.1); DBP 0.7 (-0.5, 1.9); ARV-DBP 0.1 (-0.2, 0.4)). For every one mmHg increase in ARV-SBP, there was a 4.6% significantly greater odds of stroke (OR (95%CI) 1.05 (1.02, 1.07)), while there were 1.6% greater odds of stroke for every one mmHg increase in ARV-DBP but no statistical significance (OR 1.02 (0.98, 1.05)). After adjusting for age, gender, race, ethnicity, and BMI, the odds of stroke were 2.8% significantly higher for every one mmHg increase in ARV-SBP (OR 1.03 (1.00, 1.05)) and the ARV - stroke association remained non-significant. ARV-SBP was only associated with stroke in patients who were diagnosed with a stroke at an age &lt; 50 years old, while ARV-DBP was not associated with stroke regardless of the age when the stroke was diagnosed. Conclusions: ARV-SBP in a very short interval is associated with prior history of stroke in younger than 50 years old. Impaired cerebral vasculatures may affect autoregulation in younger patients with stroke, which possibly manifests as BPV. Longitudinal cohort studies to determine the association between BPV and stroke are required.

DEDIFFERENTIATED LEIOMYOSARCOMA

ABSTRACTBACKGROUND : Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that ranges from 7-10% of all cases of soft tissue sarcoma, usually occurring in adult and elderly patients.CASE REPORT : Patient Mr. M, male, 71 years old, construction worker, Tulungagung Regency. The patient has a main complaint, namely a lump under the right armpit, felt since 2 months before visiting dr. Iskak Tulungagung.DISCUSSION : Pleomorphic LMS or dedifferentiated LMS shows nonspecific and poorly differentiated pleomorphism. To make this diagnosis, the characteristic morphological features of classic LMS must be obtained, or the patient must have a prior history of LMS. On immunohistochemistry, approximately 50–75% of pleomorphic LMS are positive for at least one myogenic marker, although the smear is often weaker and more focal than in a typical area of leiomyosarcoma.CONCLUSION: Microscopically, the morphological appearance of dedifferentiated LMS can resemble the appearance of other high-grade sarcomas, so clinical, radiological, histopathological considerations and further examinations such as immunohistochemical smears are needed.

Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease.

Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.

Onset patterns and clinical features of binge-eating disorder in a Japanese clinical sample.

This study aimed to investigate the clinical presentation of binge-eating disorder (BED) in a Japanese sample and to examine the relationship between subtypes of BED differing in onset patterns and those differing in prior history of another eating disorder (ED). The study participants were 137 adults who met the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for BED. We subtyped participants based on prior history of another ED: 55 (40.1%) participants with a history of another ED (BED ED+) and 82 participants without such a history (BED ED-). Unlike in some Western studies, approximately three quarters of participants had a body mass index of <25 kg/m2 . None of the participants reported a history of another ED with purging or excessive exercise. All BED ED+ participants transitioned to BED from anorexia nervosa restricting type (AN-R) or from atypical AN-R. BED ED+ participants reported more severe psychopathology than BED ED-participants. Only 20% had a treatment history for BED. Dieting preceded their first binge eating in 55 participants (DIET-first BED), and binge eating preceded their first dieting in 82 participants (BINGE-first BED). Regarding the relationship between the two different subtypes, all DIET-first BED participants were in the BED ED+ group, whereas all BINGE-first BED participants were in the BED ED-group. Present findings revealed the clinical presentation of BED in a Japan-based study and suggested that subtypes of BED differing in the prior history of another ED yielded an accurate prediction of onset patterns (dieting first vs. binge eating first). This study highlights the need for clinicians to consider subtype differences in onset patterns and clinical features of BED to treat and prevent this disorder. This study revealed that, although individuals with BED in Japan have severe symptoms and a long duration of illness, only 20% have received BED treatment. The results indicate a need to disseminate knowledge about BED to the Japanese public and healthcare providers.

Assessing the impact of atrial fibrillation on symptoms and quality of life in hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs). 218 consecutive HCM patients with or without AF at the Lahey HCM center in 2022 completed PROMs at their most recent visit evaluating HF (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and AF symptoms (AF Effect on QoL [AFEQT]). Among the 218 patients, 50 (23%) had a history of AF and comprise the primary study cohort. AF was diagnosed at 55 ± 10 years of age, median of 5.5 years before PROM, with 66% of patients treated with a rhythm control strategy with antiarrhythmic drug and/or AF ablation. AFEQT indicated that 52% of patients experienced no or minimal AF-related disability, mild to moderate in 22%, and severe in 26%. There was no substantial difference in HCM phenotype in patients with no or minimal AF disability compared to those with severe disability. HF symptoms for most HCM patients with prior AF history was consistent with no or minimal (59%) or only mild (27%) disability as measured by KCCQ overall summary scores. In addition, with multivariate analysis, AF history was associated with less HF symptoms and improved QoL (OR 0.4, p = 0.02). In contrast to prior perceptions, HCM patients with prior AF history were less likely to incur HF symptoms impairing QoL compared to HCM patients without AF. After treatment, prior history of AF did not substantially impact current QoL. These data provide a realistic appraisal for the impact that AF has on HCM patients and also offers a measure of reassurance for this patient subgroup.

Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum. In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.

Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.

DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study.

Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients. PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias. Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation. Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.

A rare case of fatal sepsis caused by Trichosporon asahii in an immunocompetent chronic obstructive pulmonary disease patient

Trichosporon asahii is an yeast-like organism that is emerging as an important cause of invasive fungal infection in immunocompromised patients, especially in patients with cancer and neutropenia. Invasive infections due to T.asahii in immunocompetent patients are rarely reported. We describe a 62-year-old COPD (chronic obstructive pulmonary disease) patient who contracted severe sepsis from T.asahii without any prior history of immunosuppression. He was successfully treated with voriconazole and was discharged from the hospital.

Early life seizures and epileptic spasms in STXBP1-related disorders.

Individuals with disease-causing variants in STXBP1 frequently have epilepsy onset in the first year of life with a variety of seizure types, including epileptic spasms. However, the impact of early onset seizures and antiseizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory are poorly understood, limiting informed and anticipatory treatment, as well as trial design. We retrospectively reconstructed seizure and medication histories in weekly intervals for individuals with STXBP1 developmental and epileptic encephalopathy (DEE) with epilepsy onset in the first year of life and quantitatively analyzed longitudinal seizure histories and medication response. We included 61 individuals with early onset seizures, 29 of whom had epileptic spasms. Individuals with neonatal seizures were likely to have continued seizures after the neonatal period (25/26). The risk of developing epileptic spasms was not increased in individuals with neonatal seizures or early infantile seizures (21/41 vs. 8/16, odds ratio [OR] = 1, 95% confidence interval [CI] = .3-3.9, p = 1). We did not find any ASM associated with the development of epileptic spasms following prior seizures. Individuals with prior seizures (n = 16/21, 76%) had a higher risk of developing refractory epileptic spasms (n = 5/8, 63%, OR = 1.9, 95% CI = .2-14.6, p = .6). Individuals with refractory epileptic spasms had a later onset of epileptic spasms (n = 20, median = 20 weeks) compared to individuals with nonrefractory epileptic spasms (n = 8, median = 13 weeks, p = .08). We provide a comprehensive assessment of early onset seizures in STXBP1-DEE and show that the risk of epileptic spasms is not increased following a prior history of early life seizures, nor by certain ASMs. Our study provides baseline information for targeted treatment and prognostication in early life seizures in STXBP1-DEE.

P361 Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet’s disease

Abstract Background Behçet’s disease (BD) and nonalcoholic fatty liver disease (NAFLD) are chronic inflammatory diseases that share pathogenetic mechanisms. In this study, we investigated whether NAFLD influences the clinical outcomes in patients with intestinal BD. Methods Patients with intestinal BD and available hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) scores were recruited between 2005 and 2022. An HSI of ≥30 and FIB-4 of ≥1.45 were used to diagnose hepatic steatosis and significant liver fibrosis, respectively. The primary outcomes were intestinal BD-related hospitalization, surgery, emergency room visits, or the first use of corticosteroids, immunomodulators, or biologic agents for intestinal BD. Results A total of 780 patients with BD were selected. The prevalence of hepatic steatosis and significant liver fibrosis were 72.3% and 8.8%, respectively. Multivariate analysis showed that younger age, prior smoking history, concomitant skin lesions, higher white blood cell count, and lower serum albumin levels were independently associated with an increased risk of clinical relapse (all p &amp;lt;0.05), whereas hepatic steatosis and significant liver fibrosis were not (hazard ratio [HR] = 1.164, 95% confidence interval [CI] 0.923–1.468; p = 0.199 for hepatic steatosis; HR = 0.982, 95% CI 0.672–1.436; p = 0.927 for significant liver fibrosis). Conclusion Hepatic steatosis and liver fibrotic burden were not independently associated with clinical outcomes in patients with intestinal BD.

P217 Rate of undetected dysplasia at colectomy in patients with IBD - What are we missing?

Abstract Background Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia. Methods We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both. Results Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis. In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both. In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well. Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy. Further results are shown in Table 1. Conclusion The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.

P323 Defining Normal Bowel Wall Thickness on Intestinal Ultrasound in an International Multicenter Cohort of Children with Inflammatory Bowel Disease in Sustained Deep Remission

Abstract Background Intestinal ultrasound (IUS) is a non-invasive, patient-centric tool for detecting and monitoring activity in patients with inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is the most important parameter for assessing IBD activity, however, normal values are extrapolated from adults. We aimed to define normal BWT in children with IBD who achieved sustained deep remission. Methods International, multicentre, retrospective, pediatric IUS database including IBD patients (&amp;lt; 18 years) without a prior history of surgery or complications who underwent IUS after achieving sustained deep remission: absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography or computed tomography enterography and steroid-free clinical remission from 2020-2023. Descriptive statistics summarized data as percentages for categorical variables and median [IQR] for continuous variables. Primary outcome was median BWT by segment: sigmoid colon (SC), descending colon (DC), transverse colon (TC), ascending colon (AC), and terminal ileum (TI), assessed using Kruskall Wallis. Secondary outcomes included univariate association of BWT and age, sex, disease duration, diagnosis (Crohn’s disease (CD) vs. ulcerative colitis (UC)/IBD-unspecified (IBD-U) and medication exposure. Results 80 patients (33 (41%) female; 51 (64%) CD:26 (33%)UC:3 (4%)IBD-U, median age 15.2 [14-16.6] years) with 400 bowel segments were included. Forty (50%) received anti-tumor necrosis factor therapy (anti-TNF), 18 (23%) ustekinumab (UST), 10 (12%) mesalamine(5-ASA), 6 (8%) vedolizumab (VDZ), 5 (6%) immunomodulator monotherapy (IM), and 1 (1%) upadacitinib (UPA) (Table 1). Median BWT was 1.3 [1.0-1.6]mm for SC, 1.3 [1.1-1.7]mm for DC, 1.3 [1.0-1.6] mm for TC, 1.3 [1.0-1.6]mm for AC, and 1.3 [1.1-1.5]mm for TI (Figure 1). There was no difference in BWT between segments (p=0.7952), age (p=0.1952) or sex (p=0.781). BWT was negatively associated with disease duration (p&amp;lt;0.05). UC patients had a 0.16 mm thinner BWT than CD (p&amp;lt;0.05). Mean BWT in patients on VDZ was thinner than those on anti-TNF monotherapy (-0.19mm, p&amp;lt;0.05). BWT in patients on anti-TNF combination therapy was thicker than patients on anti-TNF monotherapy (0.21mm, p&amp;lt;0.05). There was no BWT difference between patients on IM, 5-ASA and UST compared to anti-TNF (p&amp;gt;0.05). Conclusion Normal BWT for children with IBD in deep remission is less than adults, and unaffected by age, sex and bowel segment. BWT may be affected by disease duration, phenotype and medication exposure. These findings are crucial to the standardized assessment of transmural healing in children with IBD.

Lifetime history of major depressive disorder is associated with decreased reward learning: Evidence from a novel online version of the probabilistic reward task

BackgroundThe Probabilistic Reward Task (PRT) is a signal detection task that assesses reward learning. In laboratory versions of the task, individuals with current or past major depressive disorder (MDD) were characterized by reduced response bias towards a more frequently rewarded stimuli, compared to controls. Our main goal was to develop and validate a novel online version of the PRT, and, in exploratory analyses, evaluate whether lifetime history of depression was associated with blunted reward learning. Methods429 participants recruited via CloudResearch completed questionnaires assessing psychiatric history and an online PRT featuring visually appealing stimuli. 108 participants reported either current or past diagnosis of MDD (lifetime MDD group), and were compared to 321 without lifetime MDD. ResultsParticipants showed overall increase in response bias, validating the online PRT. Females with lifetime MDD (N = 43), compared to females without prior history of MDD (N = 173), exhibited blunted response bias towards the more frequently rewarded stimulus (i.e., reduced reward learning). LimitationsParticipants did not undergo a structured clinical interview, thus we cannot confirm whether they met full diagnostic criteria for depression. ConclusionsThe online PRT yielded similar psychometric properties as laboratory versions of the task. In exploratory analyses, females with lifetime MDD showed a lower propensity to modulate behavior as a function of rewards, which might contribute to heightened vulnerability for developing MDD in females. Future studies should consider social, cultural, and neurobiological factors contributing to sex differences in reward responsiveness and how factors may relate to disease prognosis and treatment outcomes.

P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging Assessments

Abstract Background Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis. Methods We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader. Results Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab. Conclusion Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.

P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort

Abstract Background Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India. Methods Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse. Results Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%). Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A). Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse. Conclusion 60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.

A systematic review of literature on homicide followed by suicide and mental state of perpetrators.

Homicide followed by suicide is rare, devastating and perpetrated worldwide. It is commonly assumed that the perpetrator had a mental disorder, raising concomitant questions about prevention. Though events have been reported, there has been no previous systematic review of the mental health of perpetrators. Our aims were twofold. First, to identify whether there are recognisable subgroups of homicide-suicides in published literature and, secondly, to investigate the relationship between perpetrator mental state and aspects of the incident. We conducted a systematic review of published literature on studies of homicide followed within 24h by suicide or serious suicide attempt that included measures of perpetrator mental state. Sixty studies were identified, most from North America or Europe. Methodologically, studies were too heterogeneous for meta-analysis. They fell into three main groups: family, mass shooter, and terrorist with an additional small mixed group. There was evidence of mental illness in a minority of perpetrators; its absence in the remainder was only partially evidenced. There was no clear association between any specific mental illness and homicide-suicide type, although depression was most cited. Social role disjunction, motive, substance misuse and relevant risk or threat behaviours were themes identified across all groups. Pre-established ideology was relevant in the mass shooter and terrorism groups. Prior trauma history was notable in the terrorist group. Research data were necessarily collected post-incident and in most cases without a standardised approach, so findings must be interpreted cautiously. Nevertheless, they suggest at least some preventive role for mental health professionals. Those presenting to services with depression, suicidal ideation, relationship difficulties and actual, or perceived, changes in social position or role would merit detailed, supportive assessment over time.