Third Of Patients Research Articles

The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression.

Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti-depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about "ATP and depression" especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression.

Improvement in Functional Outcome from 6 to 12 Months After Moderate and Severe Traumatic Brain Injury Is Frequent, But May Not Be Detected With the Glasgow Outcome Scale Extended.

The aims of this study were (1) to report outcome and change in outcome in patients with moderate and severe traumatic brain injury (mo/sTBI) between 6 and 12 months post-injury as measured by the Glasgow Outcome Scale Extended (GOSE), (2) to explore if demographic/injury-related variables can predict improvement in GOSE score, and (3) to investigate rate of improvement in Disability Rating Scale (DRS) score, in patients with a stable GOSE. All surviving patients ≥16 years of age who were admitted with mo/sTBI (Glasgow Coma Scale [GCS] score ≤13) to the regional trauma center in Central Norway between 2004 and 2019 were prospectively included (n = 439 out of 503 eligible). GOSE and DRS were used to assess outcome. Twelve-months post-injury, 13% with moTBI had severe disability (GOSE 2-4) versus 27% in sTBI, 26% had moderate disability (GOSE 5-6) versus 41% in sTBI and 62% had good recovery (GOSE 7-8) versus 31% in sTBI. From 6 to 12 months post-injury, 27% with moTBI and 32% with sTBI had an improvement, whereas 6% with moTBI and 6% with sTBI had a deterioration in GOSE score. Younger age and higher GCS score were associated with improved GOSE score. Improvement was least frequent for patients with a GOSE score of 3 at 6 months. In patients with a stable GOSE score of 3, an improvement in DRS score was observed in 22 (46%) patients. In conclusion, two thirds and one third of patients with mo/sTBI, respectively, had a good recovery. Importantly, change, mostly improvement, in GOSE score between 6 and 12 months was frequent and argues against the use of 6 months outcome as a time end-point in research. The GOSE does, however, not seem to be sensitive to actual change in function in the lower categories and a combination of outcome measures may be needed to describe the consequences after TBI.

Digital gangrene: can be the first manifestation of essential thrombocythemia? a case report

Introduction and importance: Essential thrombocythemia (ET) is a rare chronic myeloproliferative hematologic disorder, leading to an elevated platelet count. Two-thirds of patients are asymptomatic during their lifetime, while others may experience symptoms like redness, congestion, and erythromelalgia after long symptom-free intervals. Case presentation: The authors present a rare instance of a 55-year-old female who, despite receiving aspirin and losartan treatment, eventually developed digital gangrene. In further work-ups, she had an elevated platelet count and a positive JAK 2 mutation. Her platelet count was reduced throughout treatment with aspirin, hydroxyurea, and heparin, which was followed by the necrotic tip of her index finger being surgically debrided. Clinical discussion: Significant symptoms, such as severe acrocyanosis and even peripheral gangrene, can be treated with a single dose of aspirin. Daily aspirin consumption withstanding, this case developed the severe form of ET. In addition, while thrombocytosis predisposes patients to thrombotic complications in theory, there is little evidence to support a correlation between absolute platelet count and thrombosis. Conclusion: The initial symptom of ET could be such severe and uncommon that may develop arterial acral thrombosis despite previous daily low-dose aspirin consumption.

Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions

BackgroundDespite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets.MethodsWe collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis.ResultsThe bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption.ConclusionsThese results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

Is Immunotherapy Beneficial in Patients with Oncogene-Addicted Non-Small Cell Lung Cancers? A Narrative Review.

Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody-drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as "oncogene-addiction". These "driver alterations" are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC.

Multimodality Management of Thoracic Tumors: Initial Experience With a Multidisciplinary Thoracic Ablation Conference.

This study aimed to describe lesion-specific management of thoracic tumors referred for consideration of image-guided thermal ablation (IGTA) at a newly established multidisciplinary ablation conference. This retrospective single-center cohort study included consecutive patients with non-small cell lung cancer (NSCLC) or thoracic metastases evaluated from June 2020 to January 2022 in a multidisciplinary conference. Outcomes included the management recommendation, treatments received (IGTA, surgical resection, stereotactic body radiation therapy [SBRT], multimodality management), and number of tumors treated per patient. Pearson's chi-square test was used to assess for a change in management, and Poisson regression was used to compare the number of tumors by treatment received. The study included 172 patients (58 % female; median age, 69 years; 56 % thoracic metastases; 27 % multifocal primary lung cancer; 59 % ECOG 0 [range, 0-3]) assessed in 206 evaluations. For the patients with NSCLC, IGTA was considered the most appropriate local therapy in 12 %, equal to SBRT in 22 %, and equal to lung resection in 3 % of evaluations. For the patients with thoracic metastases, IGTA was considered the most appropriate local therapy in 22 %, equal to SBRT in 12 %, and equal to lung resection in 3 % of evaluations. Although all patients were referred for consideration of IGTA, less than one third of patients with NSCLC or thoracic metastases underwent IGTA (p < 0.001). Multimodality management allowed for treatment of more tumors per patient than single-modality management (p < 0.01). Multidisciplinary evaluation of patients with thoracic tumors referred for consideration of IGTA significantly changed patient management and facilitated lesion-specific multimodality management.

Acute amnestic syndrome in fornix lesions: a systematic review of reported cases with a focus on differential diagnosis

IntroductionAcute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia (TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix.MethodsWe performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded.ResultsA total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up.DiscussionAcute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.

P343 Pancreato-biliary disorders in patients with inflammatory bowel diseases – a single-centre report

Abstract Background Inflammatory bowel diseases (IBD) are regarded as multisystemic disorders due to the high prevalence of extraintestinal symptoms. Hepato-pancreato-biliary involvement can be present in up to 50% of patients, due to IBD extraintestinal manifestations and complications. Our aim was to evaluate the prevalence of the pancreato-biliary diseases in patients diagnosed with IBD. Methods We conducted a single-centre retrospective study which included patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), admitted between 1 January 2018 and 1 August 2023 in the Gastroenterology and Surgery Departments of the Fundeni Clinical Institute (Romania). We analysed the medical history (including abdominal imaging - ultrasound, computed tomography or magnetic resonance imaging) of patients during hospital follow-up and we screened for pancreato-biliary disorders. Results We analysed 1736 patients, of which 303 patients (17%) associated pancreato-biliary involvement and 756 patients (44%) had no pancreato-biliary disorders, with both subgroups having at least one abdominal imaging scan during follow-up; 677 patients (39%) had neither history of pancreato-biliary disorders, nor abdominal imaging. 30 patients (1.72% of total; 56.6% CD, 77% male) had acute pancreatitis (93.3% mild), 66.67% being drug-induced (13 cases - azathioprine, six cases - 5-amynosalicilates, one case - metronidazole). Three patients were diagnosed with idiopathic chronic pancreatitis and one with type 2 autoimmune pancreatitis. In the subgroup that underwent abdominal imaging (1059 patients) we identified 124 patients (11.70%) with pancreatic steatosis, 11 patients (1.03%) with pancreatic cysts (one case of intraductal papillary mucinous neoplasm) and three patients (0.28%) with congenital pancreatic anomalies (two annular pancreases, one pancreas divisum). There were no patients diagnosed with pancreatic adenocarcinoma. We identified 14 patients (0.8% from total; 64.28% UC, 57.14% male) with primary sclerosing cholangitis, of which five underwent liver transplantation, one case of primary biliary cholangitis and three cases of cholangiocarcinoma. The subgroup with abdominal imaging included 46 patients (4.34%) with prior cholecystectomy and 147 patients (13.88%) with gallbladder lithiasis or sludge (59.86% CD; 53.06% male; 39.45% intestinal resection). Conclusion Up to one third of patients with IBD that underwent abdominal imaging associated pancreato-biliary involvement. The high risk of drug-induced acute pancreatitis in IBD has to be taken into consideration. Screening for possible extraintestinal manifestations and early diagnosis of extraintestinal complications might improve the IBD management.

P563 Nutritional screening in patients with inflammatory bowel disease: a challenge in the timely diagnosis of malnutrition and sarcopenia

Abstract Background Malnutrition is prevalent in inflammatory bowel disease (IBD) and has been reported in up to 70% in patients with active disease and 38% in patients in remission, being related to sarcopenia, so different tools have been proposed for the nutritional screening of these patients taking into account the importance of early intervention avoiding consequences related to altered body composition such as inadequate response to treatment and poor quality of life, but the evidence in IBD patients is still unclear and there are no studies in Colombian IBD patients. Therefore, the aim of this study is to describe the nutritional status of patients using multiple nutritional screening and assessment tools. Methods Descriptive observational cross-sectional study in patients diagnosed with IBD with clinical activity, by applying nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT) to determine their nutritional status and degree of sarcopenia. Results Nutritional screening was performed in 20 patients with Inflammatory Bowel Disease, with mild to moderate clinical activity of the disease; patients in clinical remission were excluded. Sixty percent were men and 40% women; with an average age of 44.5 years, 19 years as minimum age and 73 years as maximum age. Taking into account the Malnutrition Universal Screening Tool (MUST), 30% have a high risk of malnutrition, with a higher percentage in men. On the other hand, the MIRT (Malnutrition Inflammation Risk Tool), which evaluates BMI, showed that 25% have a score greater than or equal to 3, which indicates a risk. In addition, and 40% of the population underwent nutritional status assessment in order to rule out sarcopenia. Muscle strength, muscle mass and muscle function were assessed and 25% of this population were diagnosed with sarcopenia and another 25% with possible sarcopenia. Conclusion Patients with IBD are at increased risk of malnutrition, This is the first Colombian study to approach the nutritional assessment of IBD patients with mild to moderate disease activity using nutritional screening tools such as the Malnutrition Universal Screening Tool (MUST) and the Malnutrition Inflammation Risk Tool (MIRT), showing that up to one third of patients are at high risk of malnutrition and 50% have a diagnosis or possible diagnosis of sarcopenia, which is slightly lower than that described in the literature, However, it does raise awareness of the importance of nutritional screening in IBD patients as these alterations have been shown to be associated with increased hospitalisation requirements, number of disease flares and associated complications.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

P945 Crohn´s disease response to ustekinumab measured by bowel ultrasound

Abstract Background After the STRIDE-II update for patients with Crohn’s disease (CD) one of the new possible adjunct treatment goals was transmural healing, yet its assessment is still not fully cost/risk-benefit proven. A valuable tool to assess this adjunct goal is bowel ultrasound. For this reason, our aim was to evaluate the bowel ultrasonographic response to ustekinumab at one year. Methods Retrospective, observational, single center study was designed. All adult patients with CD who were treated with ustekinumab and had a bowel ultrasound just before the induction dose with ustekinumab and who repeated the bowel ultrasound one year after it were included. Examination was done by ultrasound machine (Hitachi Avius) with low frequency curved-array (1-5 MHz) and high-frequency linear-array (5-13 MHz) transducers. The measured bowel ultrasonographic variables were: wall thickness, Doppler activity (Limberg index) and fatty striation. Ultrasonographic response was defined as a reduction in wall thickness of at least 25%, 2mm or 1mm plus 1 Doppler sign. Remission was defined as wall thickness less than 3mm plus absent Doppler sign. Patient demographics and disease characteristics were also collected: age, sex, extension of CD, previous biologic treatments and ustekinumab trough levels. Demographic and clinical characteristics were compared using χ2 analysis (or Fisher’s exact test), Student’s t test or Spearman correlation. All statistical analyses were performed using the STATA Statistical Software. Results A total of 41 patients (56.1% female) with a mean age of 57.9 years (SD ±2.7) were included. 63.4% had ileal disease and 36.6% ileocolonic involvement. Ustekinumab was first line of biologic treatment in 7.3%, second line in 61.0%, third line in 29.3% and fourth line in 2.4% of patients. 63.4% of patients were on ustekinumab 90mg subcutaneous every 4 weeks at one year with a median trough level of 8.6 (range 7.9-10.6). The median wall thickness measured by bowel ultrasound before induction was 5.5 mm (range 5.0-6.4) and after one year it was 5.0 mm (4.1-5.7) (p=0.47) Figure 1. Before treatment Limberg index was 3 in 26.8% and after treatment it was 3 in 4.9% (p=0.052). Fatty striation was present in 90.2% of patients at the beginning of treatment and in 63.4% at one year (p=0.013). Ultrasound response was achieved in 36.6% of patients while transmural remission was achieved in 12.2% of patients in the first year. No association between ustekinumab trough levels and response/remission were found (p=0.70/p=0.83) Conclusion Treatment with USK was related with an ultrasonographic response in one third of patients with refractory CD at one year. No association between ustekinumab trough levels and ultrasonographic response/remission were found

P097 Spatially resolved insights into fistulating Crohn's disease pathogenesis: Unveiling molecular heterogeneity

Abstract Background Crohn's disease (CD) frequently results in fistula development in approximately 40% of patients due to sustained, transmural inflammation within the bowel wall. Despite advanced treatments, recurrence of fistulae affects one third of patients. Understanding its pathogenesis is crucial for targeted treatments, yet remains poorly defined. This study employs spatial transcriptomic and single-cell RNA-sequencing (scRNA-seq) technologies to characterise human fistulating CD tissue pathology. Methods Unbiased FFPE spatial transcriptomics (10x Visium) were applied to surgically resected, full-thickness (FT) tissue from 20 CD-associated fistulae cases and 15 controls. Subsequently, selected cases underwent further analysis using custom 500-plex MERFISH subcellular resolution spatial transcriptomics (Vizgen MERSCOPE). Additionally, a reference single-cell cohort encompassing patients with fistulating, stricturing, and inflammatory CD phenotypes, along with healthy controls, was generated. Optimisation of scRNA-seq for resected FT ileal tissue enabled the isolation and profiling of epithelial, immune, and stromal populations (10x Chromium). Computational analysis facilitated the spatial localisation of single-cell clusters enriched in fistula CD tissue, identifying key parameters linked to fistula development. Results The scRNA-seq data revealed diverse CD-specific cellular states adopted by intestinal fibroblasts, with IL11+ fibroblasts prominently expressing CD82, COL7A1, MMP1, CHI3L1, suggestive of pro-fibrotic signalling and regenerative morphogen pathways. This coincided with the expansion of a CD-specific subpopulation of pericytes (CCL19/CCL21) involved in leucocyte migration. Spatial profiling of CD fistula tracts by Visium and MERSCOPE unveiled an enrichment of key epithelial developmental transcription factors (e.g., GRHL3) and localised the pro-fibrotic signature displaying increased IL11 and MMP expression, along with perturbed WNT signalling within the fistula stroma. Active proliferation (HOPX, MKI67) was observed at the base of fistula tracts and within the stroma. Transcriptomic characterisation depicted a gradual loss in stem cell signature (LGR5, ASCL2, SMOC2) and supporting telocytes (POSTN) toward the leading edge of the fistula, signifying abnormal epithelium loss. Conclusion This pioneering study integrates multi-modal spatial transcriptomics and single-cell profiling to unveil the intricate cellular and molecular landscape in FT, fistulating CD pathology. Spatial analyses elucidate specific mechanisms involved in epithelial loss, stromal remodelling, and perturbed WNT signalling pathways within fistulating tissue, outlining a course of disrupted regenerative processes in fistulating CD.

P1084 Persistence and efficacy of Ustekinumab in Crohn's disease after antiTNF failure. May the response of the second biologic therapy be better than the first one?

Abstract Background After antiTNF failure, a second antiTNF in Crohn's disease (CD) is effective to achieve and maintain remission, but only50% remain with the drug after 12 months of treatment. Ustekinumab (UST) has a better persistence as second-line treatment and is effective to induce and maintain long-term remission. Methods Retrospective and observational study retrieved from a prospective database of Crohn's disease patients treated with UST, after approval of Research Ethics Committee. Data were collected at the beginning of treatment and after 4, 8, 16, 24 weeks, 12, 24, 36, 48, 60 months and at the end of follow-up (UST discontinuation or March 2023 if treatment continues). Primary Objective evaluate the persistence with UST and clinical (Harvey-Bradshaw index (HBI)&amp;lt;4) and biological remission (C-reactive protein (CRP)&amp;lt;5 mg/dl and/or fecal calprotectin (FC)&amp;lt;250 mg/kg) in each period of follow up. Clinical remission in perianal disease was defined as absence of drainage both spontaneous and after soft pressure. Persistence of the first biologic therapy, reasons of treatment change, dose optimization, surgery, hospitalizations and adverse events were also evaluated. Results 68 patients were included (Table 1). Median survival of antiTNF is 1.65 years (IC95% 1.18-2.56). 72.06% patients receive antiTNF 1 year, 45.59% 2 years, 30.88% 3 years and only 8.82% are treated during 10 years. Persistence with UST was longer than with antiTNF. 93.2% of patients receive UST 1 year, 89.4% 2 years and 86.1% 3 years. There was a significant reduction of fecal calprotectin values during follow-up (p=0.0002). 7 patients with perianal disease achieved clinical remission (70.00%) and 4 complete fistula healing in magnetic resonance enterography (40.00%) at the end of follow-up. 60.29% patients received 90 mg every 8 weeks, but 36.76% required dose optimization (23.50% 90mg sq/4 weeks and 13.24%130mg/4 weeks ev). 86.76% continue UST at the end of follow-up, with a mean duration of treatment of 27.65 months (SD 18.27). 9 patients (13.24%) stopped treatment (1 primary non response, 5 loss of response, 3 adverse events). 11 patients (16.18%) needed surgery and hospitalization during follow up; 63.60% of them had stricturing disease. Conclusion Persistence with UST as a second line therapy was superior to antiTNF in first-line. 86.76% continued treatment with UST after 2 years. UST achieved early and long-term clinical remission in approximately two thirds of patients. 36.76% of patients required dose optimization. UST was effective in perianal disease after antiTNF failure. Figure 1 shows clinical remission in patients with basal HBI&amp;gt;4.

P194 Health-related quality of life and fatigue in newly-diagnosed inflammatory bowel diseases: findings from a prospective population-based inception cohort, IBD Prognosis Study

Abstract Background Patients with inflammatory bowel diseases (IBD) often experience impaired quality of life (QoL) and fatigue. In the current study, we aimed to investigate QoL and fatigue at the time of IBD diagnosis and determine their association with the disease presentation. Methods Incident adult patients (≥18 years old) with newly diagnosed ulcerative colitis (UC) or Crohn’s disease (CD) according to the Copenhagen IBD Criteria were included in the IBD Prognosis Study, a prospective, population-based, inception cohort representing approximately 20% of the Danish population (1.1 million). QoL was assessed using EQ-5D-5L and Short inflammatory Bowel Disease Questionnaires (SIBDQ), while fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A severe disease presentation was defined by the need for glucocorticoids, immunomodulators, biologics, or surgery within three months of disease. Multivariable logistical regression analyses were conducted by adjusting for gender, age, and disease phenotype. Results Out of the original cohort, 203 (65.9%) and 116 (57.7%) patients with incident UC and CD, respectively, responded to the questionnaires without differences between responders and non-responders. The mean EQ-5D-5L index values were significantly lower in patients with UC (0.82, SD 0.17) and CD (0.79, SD 0.23), compared to the Danish background population (both p&amp;lt;0.001). The difference between UC and CD was also statistically significant (p&amp;lt;0.001). Further, more than every third of patients reported severely reduced SIBDQ (UC 29.6%, CD 43.1%, p=0.04). Severe fatigue was experienced frequently at the diagnosis (UC 26.1%, CD 30.2%, p=0.43), and was more common compared to the control group (means: UC 37.2 (SD 12.0), CD 35.3 (SD 11.5), control group: p&amp;lt;0.001). Female gender and extensive UC were independently associated with severely impaired SIBDQ and fatigue in patients with UC, while EIMs were associated with both outcomes in UC and CD (Table 1). Finally, severely reduced SIBDQ and severe fatigue were independently associated with a severe disease presentation, as well as IBD-related hospitalization specifically, in both UC and CD (Figure 1). Conclusion In this prospective population-based inception cohort of newly diagnosed IBD, we found a high proportion of patients with severely impaired generic QoL, SIBDQ, and fatigue compared to healthy controls. This study emphasizes the importance of addressing these negative symptoms in patients with IBD and their prognostic impact on the disease presentation. Ref: 1. Jensen MB et al., Scand J Public Health. 2023. doi: 10.1177/14034948211058060. 2. Montan I et al., Value Health. 2018. doi: 10.1016/j.jval.2018.03.013.

Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation: Diagnostic and Therapeutic Implications.

Despite recent medical therapeutic advances, approximately one third of patients do not attain seizure freedom with medications. This drug-resistant epilepsy population suffers from heightened morbidity and mortality. In appropriate patients, resective epilepsy surgery is far superior to continued medical therapy. Despite this efficacy, there remain drawbacks to traditional epilepsy surgery, such as the morbidity of open neurosurgical procedures as well as neuropsychological adverse effects. SEEG-guided Radiofrequency Thermocoagulation (SgRFTC) is a minimally invasive, electrophysiology-guided intervention with both diagnostic and therapeutic implications for drug-resistant epilepsy that offers a convenient adjunct or alternative to ablative and resective approaches. We review the international experience with this procedure, including methodologies, diagnostic benefit, therapeutic benefit, and safety considerations. We propose a framework in which SgRFTC may be incorporated into intracranial EEG evaluations alongside passive recording. Lastly, we discuss the potential role of SgRFTC in both delineating and reorganizing epilepsy networks.

FIVE-YEAR MORTALITY FOLLOWING TRAUMATIC CENTRAL CORD SYNDROME IN WALES

AimsTraumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in a motor impairment affecting the upper limbs more than the lower limbs, with occasional sensory impairment and urinary retention seen. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study is to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age.Patients and MethodsPatients ≥18 years with traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and injury, management and outcome data was collected. Statistical analysis was performed to assess mortality and between group differences.Results65 patients were identified (66.2% male, mean age 63.9 years). At five-years follow-up, 32.3% (n=21) of CCS patients were dead. 6 (9.2%) patients had died within 31 days of their injury. 69.2% (n=45) of patients were managed conservatively and there was no significant difference (p=0.062) in age between conservatively and surgically managed patients. Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively compared to those managed surgically (log rank test, p=0.819). However, there was a significant difference (p=0.001) in mortality between the different age groups (&lt;50 years vs 50–70 years vs &gt;70 years). At five-years follow up, 55.6% of the patient group aged &gt;70 years at time of injury were dead. Respiratory failure was the most common cause of death (n=9, 42.9%).ConclusionAlmost one third of patients with traumatic CCS in Wales were dead at five years following their injury. Management type did not significantly affect mortality, however age at time of injury did. Further work assessing the long-term functional outcomes of surviving patients is needed, to allow more reliable prognostic information and functional recovery predictions to be given.

Outcomes and prognostic factors of advanced biliary tract cancers in Saudi Arabia.

460 Background: Biliary tract cancers which include gallbladder adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma are rare, and carry a poor prognosis. There is limited data on biliary tract cancers in the Saudi population. Methods: This single center retrospective study was conducted with data of eligible cases from the last 4 years. Survival, chemotherapy regimens, and variables such as neutrophil to lymphocyte ratio (NLR), and other potential prognostic variables were collected. Results: The study included 155 patients of which 75 had intrahepatic cholangiocarcinoma and 74 had gallbladder adenocarcinoma. The majority were females at 63% of patients. Overweight to obese patients represented 59% of the study cohort. The majority of patients (62%) had an ECOG performance status of 2 and below. Comprehensive genomic profiling was done to 20% of cholangiocarcinoma cases. Elevated CA19-9 tumor marker (&gt; 37 micromol/L) was found in 57% of patients. De novo metastatic disease affected 82% of patients. One third of patients (33%) were not fit for first line chemotherapy, and were given best supportive care. First line chemotherapy of platinum + gemcitabine was given to 53% of fit patients, followed by gemcitabine alone given to 38%, followed by 5-Fluorouracil chemotherapy given to 9% of patients. Very few patients lived for 12 months or more at 16%. There was a significant association between NLR and progression free survival (PFS) with median PFS being 3.5 months in the NLR &gt; 3 group (95% CI 1.2-6 months) versus median PFS of 9.8 months in the NLR &lt; 3 group (95% CI 7.5-12 months, p=0.019). Conclusions: Biliary tract cancers still carry a poor prognosis. NLR ratio of more than 3 was found to predict a low PFS.

Oxaliplatin desensitization in patients with GI malignancies: Experience from a tertiary cancer center.

89 Background: Oxaliplatin hypersensitivity is not uncommon in patients with gastrointestinal (GI) cancers receiving chemotherapy. The use of oral premeditations (dexamethasone, cetirizine and famotidine) starting 24 hours before treatment and continuing for a total of three days, further intravenous premedication (dexamethasone, chlorphenamine and famotidine) 30 minutes before treatment and the gradual administration of oxaliplatin over 6.5 hours in four separate escalating doses (desensitisation protocol) is commonly used in such cases. While desensitisation is an option, especially in severe cases, responses and survival outcomes upon rechallenge are not well described. Methods: A retrospective chart review of patients with various GI malignancies who received oxaliplatin-based desensitisation chemotherapy after a severe drug reaction between October 2019 and October 2022 at a single cancer centre was performed. Clinicopathological characteristics and oncological outcomes were assessed. Results: Forty-four patients with a median age of 61 years (range 38-81) were studied. The majority had a diagnosis of CRC (n=22; 50%), followed by oesophago-gastric (n=19; 4%), appendiceal (n=1), cholangiocarcinoma (n=1), and cancer of unknown primary (n=1). More than two thirds of patients (n=32, 73%) were treated with palliative intent. The most common regimens associated with oxaliplatin hypersensitivity reactions after a median of 3 cycles (range 1-10) were FOLFOX (n=24, 55%), CAPOX (n=18, 41%), FLOT (n=1) and FOLFOXIRI (n=1). Seven patients (16%) had another reaction after desensitisation, leading to discontinuation of treatment. Thirty-seven patients (84%) completed treatment as planned. Treatment outcomes after desensitisation included 5 (11%) patients with no evidence of disease (NED) after adjuvant treatment, 16 (37%) patients with disease control, including 3 (7%) partial responders (PR) and 13 (30%) patients with stable disease (SD), and 23 (52%) patients with progressive disease (PD). Conclusions: Oxaliplatin desensitisation is feasible with low discontinuation rates and leads to acceptable oncological outcomes. All patients should be offered desensitisation to allow continuation of active systemic therapy.

Virtual twins for model-informed precision dosing of clozapine in patients with treatment-resistant schizophrenia.

Model-informed precision dosing using virtual twins (MIPD-VTs) is an emerging strategy to predict target drug concentrations in clinical practice. Using a high virtualization MIPD-VT approach (Simcyp version 21), we predicted the steady-state clozapine concentration and clozapine dosage range to achieve a target concentration of 350 to 600 ng/mL in hospitalized patients with treatment-resistant schizophrenia (N = 11). We confirmed that high virtualization MIPD-VT can reasonably predict clozapine concentrations in individual patients with a coefficient of determination (R2 ) ranging between 0.29 and 0.60. Importantly, our approach predicted the final dosage range to achieve the desired target clozapine concentrations in 73% of patients. In two thirds of patients treated with fluvoxamine augmentation, steady-state clozapine concentrations were overpredicted two to four-fold. This work supports the application of a high virtualization MIPD-VT approach to inform the titration of clozapine doses in clinical practice. However, refinement is required to improve the prediction of pharmacokinetic drug-drug interactions, particularly with fluvoxamine augmentation.

Joint bleeds in mild hemophilia: Prevalence and clinical characteristics.

Joint bleeds are a common and frequent complication associated with hemophilia, increasing the risk of hemophilic arthropathy. It is important to define and characterize the presence of joint complications in mild hemophilia to develop strategies to mitigate disease burden. To characterize the prevalence, clinical characteristics of joint bleeds, and risk factors that may lead to hemarthrosis in people with mild hemophilia. Following Institutional Review Board approval, a retrospective chart review was conducted for patients with mild hemophilia seen at the Yale Hemophilia Treatment Center or Classical Hematology Program. The medical records of 70 patients were reviewed. Eighty one percent were male and 19 percent were female. Twenty individuals with mild hemophilia had a history of joint bleeding, 13 were traumatic bleeds, 7 were spontaneous. The age of first joint bleed ranged from 4 to 58 years old, with an average age of 20.8-years old. Ten patients developed joint bleeds between the ages of 10 and 20 years old. The most common locations of joint bleeding were the knee (n=11) and ankle (n=7). Eight of 70 patients had hepatitis C (HCV), 6 experienced joint bleeding. In this study, almost one third of patients with mild hemophilia experienced joint bleeding, often without history of trauma. Joint range of motion was abnormal in more than a third of the patients with mild hemophilia regardless. These data highlight the need for ongoing evaluation and characterization of joint health in individuals with mild hemophilia. Twenty-nine percent of individuals with mild hemophilia had history of joint bleed. PwH and mild diseases with previous or current hepatitis C had higher likelihood of joint bleeding. Approximately 15% of PwH and mild diseases had abnormal joint examinations without a confirmed history of joint bleeding.