Short-term Remission Research Articles

Acute severe ulcerative colitis: using JAK-STAT inhibitors for improved clinical outcomes

Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

Remission of hypertension after laparoscopic sleeve gastrectomy versus Roux-en-Y-gastric bypass: a systematic review of randomized control trials

BackgroundBesides its benefits for weight loss, current findings suggest that bariatric surgery can induce remission of hypertension. Limited data report the effect of bariatric surgery on this obesity-associated comorbidity. ObjectiveCompare the short-term, mid-term, and long-term remission of hypertension after sleeve gastrectomy versus Roux-en-Y gastric bypass. SettingMeta-analysis of randomized controlled trials (RCTs). MethodsFour databases (Embase, PubMed, Scopus, and Science Direct) were searched for RCTs that compared the effects of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on hypertension remission at <1 year, 2–4 years, and ≥5 years. Patients with a history of hypertension and who had primary bariatric surgery were included. ResultsAfter reviewing 11,814 studies, only 11 RCTs were included. In total, the analysis included 2323 patients, with 1158 in the SG group (49.85%) and 1165 in the RYGB group (50.15%). It was found that SG and RYGB procedures had comparable hypertension remission at ≤1 year (Relative risk: 1.11, 95% CI .83–1.48, P = .49), and between 2 and 4 years (Relative risk: 1.11, 95% CI .90–1.37, P = .34). However, there was a significant difference in hypertension remission at ≥ 5 years, favoring RYGB (relative risk: 1.39, 95% CI 1.06–1.82, P = .02). ConclusionThis systematic review and meta-analysis of RCTs demonstrates that RYGB is superior to SG in resolving hypertension beyond 5 years postoperatively. These findings highlight the long-term benefits of RYGB over SG in managing hypertension, providing valuable insights for surgical decision-making and patient counseling.

The Role of Endoscopic Transsphenoidal Surgery in Microprolactinomas: A Retrospective Study

Most patients with microprolactinomas have to take dopamine agonist for a lifetime. Many of them in our center have consulted endoscopic transsphenoidal surgery as an alternative therapy. The current study is a retrospective cohort analysis of 42 patients with microprolactinoma underwent endoscopic transsphenoidal surgery between January 2010 and December 2023 by experienced neurosurgeons in our center. The mean follow-up duration was 30.17 months (range, 13.00-45.40). The short-term (postoperative day 1) remission rate was 95.24% and the long-term (over 1-year follow-up) remission rate was 92.86%. As to remission, the pattern of prolactin level changes on postoperative day 1 was significantly associated with recurrence. In hypoprolactinemia group, all 29 patients showed remission at the 1-year follow-up. In patients with normal PRL levels, 10 out of 11 patients showed remission, while 1 out of 11 patients showed recurrence at the 1-year follow-up. In hyperprolactinemia group, all 2 patients showed recurrence at the 1-year follow-up. Moreover, adenoma location was significantly associated with recurrence as well. In the recurrent group (3 patients), 2 patients belonged to the uncertain group, while the other patient belonged to the lateral group. The surgical complications were temporary and resolved shortly after surgery. According to our findings, endoscopic transsphenoidal surgery performed on patients with microprolactinomas at advanced pituitary tumor centers could be an option with high success rates and low complications. Moreover, improving MRI imaging techniques and/or multidisciplinary team discussion before surgery for microprolactinoma could improve tumor remission after surgery.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition.

Intrapancreatic fat deposition (IPFD) exerts a significant negative impact on patients with type 2 diabetes mellitus (T2DM), accelerates disease deterioration, and may lead to impaired β-cell quality and function. To investigate the correlation between T2DM remission and IPFD. We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023, including 40 patients with weight loss-induced T2DM remission (research group) and 40 patients with short-term intensive insulin therapy-induced T2DM remission (control group). We comparatively analyzed improvements in IPFD [differential computed tomography (CT) values of the spleen and pancreas and average CT value of the pancreas]; levels of fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and insulin; and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Correlation analysis was performed to explore the association between T2DM remission and IPFD. After treatment, the differential CT values of the spleen and pancreas, FBG, 2hPBG, and HOMA-IR in the research group were significantly lower than those before treatment and in the control group, and the average CT value of the pancreas and insulin levels were significantly higher. Correlation analysis revealed that the greater the T2DM remission, the lower the amount of IPFD. T2DM remission and IPFD are inversely correlated.

Mortality in relation to diabetes remission in Swedish Obese Subjects -a prospective cohort study.

People with obesity and type 2 diabetes (T2D) have reduced life expectancy, partly explained by increased risk of cardiovascular diseases and cancer. Here, we examined whether 2-year diabetes remission after bariatric surgery or usual care is associated with long-term mortality. This report includes 586 participants with obesity and concomitant T2D from the prospective Swedish Obese Subjects (SOS) cohort study; 338 underwent bariatric surgery and 248 received usual obesity care. At inclusion, age was 37-60 years and BMI ≥34kg/m2 in men and ≥38kg/m2 in women. Median follow-up was 26.2 years (interquartile range 22.7-28.7). Diabetes status was determined using self-reported data on diabetes medication and in-study measures of blood glucose and HbA1c. The study was cross-linked to Swedish national registers for data on morbidity, death, and emigration. Overall, 284 participants, 71.9% of surgery and 16.5% of usual care patients, were in remission at the 2-year examination. During follow-up, mortality rates were 16.6 deaths per 1000 person-years (95% CI:13.7-20.1) in the remission subgroup and 26.0 deaths per 1000 person-years (95% CI:22.2-30.4) in the non-remission subgroup (adjusted hazard ratio (HRadj)=0.71, 95% CI:0.54-0.95, P=0.019). The adjusted median life expectancy in the remission subgroup was 2.5 years (95% CI:0.3-4.7) longer than in the non-remission subgroup. Specifically, remission was associated with decreased cardiovascular mortality (sub-HRadj=0.54, 95% CI:0.35-0.85, P=0.008), but no detectable association with cancer mortality was found (sub-HRadj=1.06, 95% CI:0.60-1.86), P=0.841). In this post-hoc analysis of data from the SOS study, patients who achieved short-term diabetes remission had increased life expectancy and decreased cardiovascular death over up to 32 years of follow-up. Future studies should confirm these findings.

A potential best-in-class BCMA-CD19 bispecific CART with advanced safety by self-inhibiting IFNG signaling during CRS.

2502 Background: CART cells have demonstrated remarkable clinical efficacy in treating hematological cancers. However, CRS remains as a major challenge in clinical application, with multiple cytokines significantly elevated. IL6 signaling blockade by Tocilizumab has become a standard treatment to relieve CRS in patients. Our previous studies suggested that CAR T secreting IL6 antagonist could effectively maintain IL6 at very low levels during CRS. Furthermore, we observed that a huge quantity of tumor cells in one patient was significantly reduced after CART infusion, but a low level of IFNG with only grade 2 CRS was present. Therefore, we hypothesized that high level of IFNG might not be necessary to CART clinical efficacy and direct blockade of IFNG signaling by CART secreting an IFNG antagonist (designated as SAFET) serves an interesting approach to effectively reduce CRS toxicity. Although IFNG is usually thought important in T cell cytotoxicity, our results indicated that IFNG KO or autonomous secretion of IFNG antagonist did not affect the killing activity of CART cells. Methods: This pilot phase 1 study of SAFET BCMA/CD19 BiCART self-inhibiting IFNG signaling is a single arm study conducted in China, enrolling refractory/relapsed multiple myeloma patients. The patients had received more than 3 lines of prior therapies including at least a proteasome inhibitor and an immunomodulatory agent and were refractory to the last line of treatment. Lymphodepletion was performed with fludarabine and cyclophosphamide prior to the CART infusion. Following 2-14 days of rest, patients received a single infusion of SAFET BCMA/CD19 BiCART, at the dose of 0.4-1.0 × 108 CAR+ T cells/patient. The primary objectives of this study were to evaluate the safety and efficacy of SAFET BCMA/CD19 BiCART. The pharmacokinetics of SAFET BCMA/CD19 BiCART was investigated by quantitative PCR based detection of CAR vector copies in peripheral blood. Minimal residual disease (MRD) negativity was assessed by standardized multicolor flow cytometry analysis of bone marrow aspirate. Results: 10/11 R/R MM patients achieved CR and 1 achieved VGPR. Among the 10 CR patients, 7 remained CR after treatment with a median PFS 858 days; 1 patient showed relapse at Days 215; 2 patients showed MRD positive relapse at Days 637 and 733, and then received KRd and/or Kd treatment to achieve SD and MRD negative CR. Interestingly, the remarkable short and long term remission suggested that CART self-inhibiting IFNG signaling did not impair the CART clinical efficacy. Notably, minimal CRS was observed, including 6 grade 0, 2 grade 1, 2 grade 2, and 1 grade 3 who displayed mild transient hypotension for only 1 day while there were 79.5% blast tumor cells in the bone marrow before CART therapy. Conclusions: These results suggest BCMA-CD19 bispecific CART self-inhibiting IFNG signaling is promising in translation to a best-in-class treatment for MM. Clinical trial information: ChiCTR2000032124.

Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent.

Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Clinical case of a patient with advanced metabolic syndrome following bariatric surgery

Introduction: The escalating prevalence of Type 2 Diabetes Mellitus (T2DM), with its inherent risk of severe complications, underscores the urgency for innovative therapeutic approaches. Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures(1) Clinical case: From 03.23 (photo 1) Anamnesis: A 40-year-old female patient with newly diagnosed type 2 diabetes, obesity grade III, dyslipidaemia, and liver steatosis S3, F3-4 (Metabolic syndrome). Gained 30 kg in the last year, with no effect from weight loss attempts. History of gestational diabetes in 2006. Status: Centripetal accumulation of adipose tissue. Weight 140 kg, BMI 43. Clinical-laboratory investigations: CGM – 7.2- 10.9-10.62-8.58 mmol/l, HbA1c 7.8%; Treatment: Bariatric surgery with mini-gastric bypass laparoscopy and cholecystectomy was performed in March 2023. Follow-up since March 2024 (photo 2): Status: Weight- 82 kg; BMI- 27; Reduction of 58 kg so far. Clinical-laboratory investigations: CGM: 4.12-5.8-3.63-3.78mmol/l; HbA1c 5.1%. Conclusion: Bariatric surgery is an increasingly adopted approach in the treatment of type 2 diabetes and obesity, leading to short-term complete remission of diabetes and metabolic markers. Moreover, modern bariatric procedures have strong evidence of efficacy and safety. All patients with severe obesity-and especially those with type 2 diabetes-should be informed about the risks and benefits of surgery compared with continuing usual medical and lifestyle treatment, and the decision about surgery should be driven primarily by informed patient preferences (2).

18F]FET PET/MRI: An Accurate Technique for Detection of Small Functional Pituitary Tumors.

Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain. This excludes patients from surgical, Gamma Knife, and CyberKnife therapy and adversely affects overall cure rates. We here assess the diagnostic yield of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET/MRI for detection of small functional pituitary tumors in these patients. Methods: This retrospective analysis included patients with Cushing disease (CD) but prior negative or inconclusive MRI results who underwent [18F]FET PET/MRI between February 1, 2021, and December 1, 2022. PET/MR images and MR images alone were evaluated by experienced nuclear radiologists, neuroradiologists, or radiologists. Postoperative tissue analysis (when performed) was used as a reference standard to assess diagnostic metrics (i.e., sensitivity and positive predictive value). Results were also compared with previously obtained MR images, preceding IPSS, and clinical or biochemical follow-up. Results: Twenty-two patients (68% female; mean age ± SD, 48 ± 15 y; range, 24-68 y) were scanned. All patients showed a clear metabolic focus on [18F]FET PET, whereas reading of the MRI alone yielded a suspected lesion in only 50%. Fifteen patients underwent surgery directed at the [18F]FET-positive focus. Tissue analysis confirmed a pituitary adenoma/pituitary neuroendocrine tumor of the corticotroph cell type (TPIT lineage) in 10 of 15 and a pituicytoma in 1 of 15, rendering a sensitivity of 100% and a positive predictive value of 73%. Lateralization was more accurate with [18F]FET PET/MRI than with IPSS in 33%. Twelve of 16 (75%) patients who received surgical, Gamma Knife, or CyberKnife therapy after [18F]FET PET/MRI reached short-term remission. Conclusion: [18F]FET PET/MRI shows a high diagnostic yield for localizing small functional pituitary tumors. This multimodal imaging technique provides a welcome improvement for diagnosis, planning of surgery, and clinical outcome in patients with Cushing disease, particularly those with repeated negative or inconclusive MRI results with or without IPSS.

Safety and Efficacy of LSG Versus LRYGB on Patients with Obesity: a Systematic Review and Meta-analysis from RCTs.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are the two most frequently performed techniques in treating obesity and its related comorbidities. We aimed to compare the clinical efficacy and safety of LSG with LRYGB in terms of short- and mid-term outcomes of weight loss, obesity-related comorbidities, and post-operative complications via a meta-analysis of RCTs. Clinical comparative RCTs on LSG and LRYGB were searched through PubMed, MEDLINE, and Web of Science databases from inception to August 2022. Pooled outcomes from the selected studies were discussed by the random-effect meta-analysis method. Quality assessment and risk of bias for selected RCTs were implemented, and all the statistical analyses were performed. Twenty studies, including 1270 patients, were enrolled. Meta-analysis results indicated the great superior efficacy of LRYGB to LSG in BMI loss at 6 (MD -1.35kg/m2, 95% CI: -2.07 to -0.62, p = 0.0003), 12months (MD -1.09kg/m2, 95% CI: -1.86 to -0.33, p = 0.005), and 36months (MD -1.47kg/m2, 95% CI: -2.77 to -0.16, p = 0.03) as well as %EWL gaining at 36months. Significantly higher remission rates of T2DM and dyslipidemia were achieved by LRYGB at 12months. Besides, better improvements for T2DM-related and lipid biochemical parameters were found favoring LRYGB. However, LSG resulted in a lower post-operative complication rate and shorter operating time. Present meta-analysis results suggested that LRYGB was superior to LSG concerning short- and mid-term weight loss, short-term T2DM remission efficacy, and related biochemical parameters. LSG is favored for obviously fewer complications and shorter operating time.

Unilateral Primary Aldosteronism: Long-Term Disease Recurrence After Adrenalectomy.

Primary aldosteronism (PA) is frequently caused by a unilateral aldosterone-producing adenoma with a PA-driver mutation. Unilateral adrenalectomy has a high probability of short-term biochemical remission, but long-term postsurgical outcomes are relatively undefined. Our objective was to investigate the incidence of long-term recurrence of PA in individuals with postsurgical short-term biochemical remission. Adrenalectomized patients for unilateral PA were included from a single referral center. Histopathology and outcomes were assessed according to international histopathology of unilateral primary aldosteronism and PASO (Primary Aldosteronism Surgical Outcome) consensuses. Genotyping was performed using CYP11B2 (aldosterone synthase)-guided sequencing. Classical adrenal histopathology, exemplified by a solitary aldosterone-producing adenoma, was observed in 78% of 90 adrenals, compared with 22% with nonclassical histopathology. The classical group displayed higher aldosterone-to-renin ratios (P=0.013) and lower contralateral ratios (P=0.008). Outcome assessments at both short (12 months [7; 12]) and long (89 months [48; 124]) terms were available for 57 patients. At short-term assessment, 53 (93%) displayed complete biochemical success (43 classical and 10 nonclassical), but long-term assessment demonstrated biochemical PA recurrence in 12 (23%) with an overrepresentation of the nonclassical histopathology (6 [60%] of 10 nonclassical histopathology versus 6 [14%] of 43 classical histopathology; P=0.005). PA-driver mutations were identified in 97% of 64 aldosterone-producing adenomas; there was no association of the aldosterone-producing adenoma genotype with PA recurrence. A substantial proportion of individuals display postsurgical biochemical recurrence of PA, which is related to the histopathology of the resected adrenal gland. These findings emphasize the role of histopathology and the requirement for continued outcome assessment in the management of surgically treated patients for PA.

P569 Persistence and safety of upadacitinib in Crohn’s disease and ulcerative colitis in real life: results from a Spanish nationwide study

Abstract Background Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA. Methods Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index &amp;gt;4 in CD, and partial Mayo score &amp;gt;2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively. Results One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1). Conclusion In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.

Successful Resolution of Messianic Delusion following Bi-temporal Modified Electroconvulsive Therapy in a Patient with Treatment-resistant Schizophrenia

Messianic delusion comprises a delusional system centered on the patient’s conviction that he has been selected by God for a special task or mission and has unique abilities to carry it out. The present case report describes a case of Treatment-Resistant Schizophrenia (TRS) with Messianic delusion in a 23-year-old unmarried male who presented to the Emergency Department with complaints of muttering to himself, decreased sleep, suspiciousness, socio-occupational dysfunction, aggressive behaviour, and a recent suicide attempt. Key interventions offered during the ward stay included rapid tranquilisation, antipsychotics, and benzodiazepines. The patient completely recovered with the concurrent use of clozapine and Modified Electroconvulsive Therapy (MECT). The patient received 16 sessions of MECT. He achieved both short-term and long-term remission with the therapy, as observed during regular follow-ups in the next six months. The present case emphasises the need for a multidisciplinary approach to the management, early detection, and adequate treatment of this challenging illness.

Successful Resolution of Messianic Delusion following Bi-temporal Modified Electroconvulsive Therapy in a Patient with Treatment-resistant Schizophrenia

Messianic delusion comprises a delusional system centered on the patient’s conviction that he has been selected by God for a special task or mission and has unique abilities to carry it out. The present case report describes a case of Treatment-Resistant Schizophrenia (TRS) with Messianic delusion in a 23-year-old unmarried male who presented to the Emergency Department with complaints of muttering to himself, decreased sleep, suspiciousness, socio-occupational dysfunction, aggressive behaviour, and a recent suicide attempt. Key interventions offered during the ward stay included rapid tranquilisation, antipsychotics, and benzodiazepines. The patient completely recovered with the concurrent use of clozapine and Modified Electroconvulsive Therapy (MECT). The patient received 16 sessions of MECT. He achieved both short-term and long-term remission with the therapy, as observed during regular follow-ups in the next six months. The present case emphasises the need for a multidisciplinary approach to the management, early detection, and adequate treatment of this challenging illness.

Prediction of Clinical Remission with Adalimumab Therapy in Patients with Ulcerative Colitis by Fourier Transform-Infrared Spectroscopy Coupled with Machine Learning Algorithms.

We aimed to develop prediction models for clinical remission associated with adalimumab treatment in patients with ulcerative colitis (UC) using Fourier transform-infrared (FT-IR) spectroscopy coupled with machine learning (ML) algorithms. This prospective, observational, multicenter study enrolled 62 UC patients and 30 healthy controls. The patients were treated with adalimumab for 56 weeks, and clinical remission was evaluated using the Mayo score. Baseline fecal samples were collected and analyzed using FT-IR spectroscopy. Various data preprocessing methods were applied, and prediction models were established by 10-fold cross-validation using various ML methods. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed a clear separation of healthy controls and UC patients, applying area normalization and Pareto scaling. OPLS-DA models predicting short- and long-term remission (8 and 56 weeks) yielded area-under-the-curve values of 0.76 and 0.75, respectively. Logistic regression and a nonlinear support vector machine were selected as the best prediction models for short- and long-term remission, respectively (accuracy of 0.99). In external validation, prediction models for short-term (logistic regression) and long-term (decision tree) remission performed well, with accuracy values of 0.73 and 0.82, respectively. This was the first study to develop prediction models for clinical remission associated with adalimumab treatment in UC patients by fecal analysis using FT-IR spectroscopy coupled with ML algorithms. Logistic regression, nonlinear support vector machines, and decision tree were suggested as the optimal prediction models for remission, and these were noninvasive, simple, inexpensive, and fast analyses that could be applied to personalized treatments.

Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus.

Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram. In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model. Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability. The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

SP6.1 Short-term and long-term remission of Type 2 diabetes mellitus after Sleeve Gastrectomy (SG) vs One-Anastomosis Gastric Bypass (OAGB) vs Roux-en-Y Gastric Bypass (RYGB): A Narrative Literature Review

Abstract Aim The three most widely performed bariatric surgeries are RYGB, SG, and OAGB. Aside from the benefits of weight loss, current findings suggest that these procedures can also induce remission of T2DM. There are limited data that directly compare these three procedures. This study aims to compare the short-term and long-term remission of T2DM after RYGB, SG, and OAGB. Methods Three databases (Embase, PubMed, and Cochrane) were searched for randomised controlled trials, systematic reviews, meta-analyses, retrospective studies, and literature reviews that compared the effects of RYGB, SG, and OAGB on T2DM remission. The studies were published over a ten-year period (2012 - 2022). Only patients with T2DM and who had primary bariatric surgery were included. Results After applying the inclusion and exclusion criteria, six articles were included in the review. It was found that OAGB had superior T2DM remission and weight loss in the short-term and long-term follow-up. RYGB was noted to have the highest complication rate when compared to SG and OAGB. Moreover, in one of the studies, patients who were not taking insulin had a higher remission rate than those taking insulin. Conclusion This narrative literature review confirms the existing data that all three bariatric surgeries induce remission of T2DM. With the limited studies available that compared all three procedures, OAGB was found to be the superior procedure in terms of weight loss and inducing remission of T2DM. It is also worth noting that there are other independent predictive factors that have an impact on T2DM remission.

Low prevalence of subclinical synovitis in patients with juvenile idiopathic arthritis (JIA) in long-term clinical remission on medication.

Subclinical synovitis is highly prevalent in patients with JIA in clinical remission (CR) with a short duration. The objective was to evaluate its prevalence by ultrasound (US) in patients with JIA in long CR during a one-year follow-up. In this prospective and longitudinal study, we included 76 patients with JIA according to ILAR with CR by the Wallace modified criteria and JADAS27 and compared them with 22 patients with active disease. Clinical and demographic characteristics were recorded. US evaluation was by 10-joint count. Differences in US evaluations were analyzed by the Mann-Whitney U test. There were no differences among the two group with regard to disease duration at enrollment, and age (p = 0.540 and p = 0.080, respectively), but JADAS 27, CHAQ, and acute phase reactants were significantly higher (p < 0.001) in the clinically active group. The prevalence of subclinical synovitis at baseline and the end of the study in the CR group was 18.4% and 11.8%, respectively, while it was 100% and 40.9% in the active disease group. Subclinical synovitis at baseline was significantly more prevalent in the clinically active group (elbow, p = 0.01; wrist, p = 0.001; MCP 2, p = 0.001; knee, p = 0.001 and ankle p = 0.001; and PD only in the ankle, p = 0.002). The concordance of inter-reader reliability in all evaluated joints was excellent (p = 0.001). Although the prevalence of subclinical synovitis is low in patients with JIA with long-term clinical remission on medication, a percentage of patients continue to have subclinical involvement that could predict the risk of relapse and structural damage. Key Points • Subclinical synovitis is less prevalent in JIA in long-term clinical remission compared to patients in short-term remission. • The persistence of imaging signs of inflammation in a significant percentage of patients may indicate the need for ongoing medication.

Transition Metal-Based Therapies for Inflammatory Diseases.

Inflammatory disease (ID) is a general term that covers all diseases in which chronic inflammation performs as the major manifestation of pathogenesis. Traditional therapies based on the anti-inflammatory and immunosuppressive drugs are palliative with the short-term remission. The emergence of nanodrugs has been reported to solve the potential causes and prevent recurrences, thus holding great potential for the treatment of IDs. Among various nanomaterial systems, transition metal-based smart nanosystems (TMSNs) with unique electronic structures possess therapeutic advantages owing to their large surface area to volume ratio, high photothermal conversion efficiency, X-ray absorption capacity, and multiple catalytic enzyme activities. In this review, the rationale, design principle, and therapeutic mechanisms of TMSNs for treatments of various IDs are summarized. Specifically, TMSNs can not only be designed to scavenge danger signals, such as reactive oxygen and nitrogen species and cell-free DNA, but also can be engineered to block the mechanism of initiating inflammatory responses. In addition, TMSNs can be further applied as nanocarriers to deliver anti-inflammatory drugs. Finally, the opportunities and challenges of TMSNs are discussed, and the future directions of TMSN-based ID treatment for clinical applications are emphasized.