Lower Remission Rate Research Articles

Leukocytosis in Cushing's syndrome persists post-surgical remission and could predict a lower remission prognosis in patients with Cushing's disease.

Leukocytosis frequently noted in Cushing's syndrome (CS), along with other blood cell changes caused by direct and indirect cortisol effects. Assess baseline white blood cell (WBC) profile in CS patients compared to controls and WBC changes pre- and post-remission after surgical treatment for CS. A comparative nationwide retrospective cohort study. Data from Clalit Health Services database. 297 patients (mean age 51 ± 16.1 years, 73.0% women) with CS and 997 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS or adrenal cancer patients were excluded. Mean WBC, neutrophils, and neutrophil-to-lymphocyte ratio (NLR) two-years before and after pituitary or adrenal surgery. WBC and neutrophils are expressed as Kcells/µl. At baseline, leukocytosis was observed in 21.5% of patients with CS vs. 8.9% of controls (P < 0.001). Patients with CS had significantly higher WBC (8.8 ± 2.88 vs. 7.54 ± 2.45, p < 0.0001), neutrophils (5.82 ± 2.38 vs. 4.48 ± 1.97, p < 0.0001), and NLR (3.37 ± 2.63 vs. 2.27 ± 1.86, p < 0.0001) compared to controls, regardless of pituitary or adrenal source of hypercortisolemia. Post-surgery, patients with CS experienced significant decreases in mean WBC (-0.57 ± 2.56, p < 0.0001), neutrophils (-0.84 ± 2.55, p < 0.0001), and NLR (-0.63 ± 2.7, p < 0.0001). Despite achieving disease remission, patients with CS still had higher WBC (8.11 ± 2.4 vs. 7.46 ± 2.17, p = 0.0004) and neutrophils (4.71 ± 2.10 vs. 4.41 ± 1.87, p = 0.03) compared to controls. Patients with CD and baseline leukocytosis had lower remission rate than those with normal WBC (36.7% vs. 63.9%, p = 0.01). At diagnosis, CS patients have elevated WBC, neutrophils, and NLR compared to controls. Remission does not normalize WBC levels in all patients, and baseline leukocytosis predicts a poorer remission prognosis in CD.

P0994 Effectiveness of Risankizumab in an Emirati Crohn’s Disease Cohort: Real-World Insights on Induction, Maintenance, and Dose Intensification Outcomes

Abstract Background Risankizumab, an IL-23 inhibitor, has shown efficacy in RCTs and real-world studies for inducing and maintaining clinical remission in Crohn’s disease (CD) patients. We report the largest real-world evidence from the Middle East evaluating risankizumab’s effectiveness and safety in advanced therapy (AT) naive and exposed patients along with outcomes following dose intensification. Methods A prospective observational study in an Emirati cohort at tertiary IBD center in UAE evaluated clinical outcomes at induction (3-5 months) and maintenance (12-14 months), assessing clinical remission (CDAI &amp;lt;150), clinical response (CDAI improvement by 100 points) and endoscopic response (≥50% SES-CD improvement). Long-term outcomes following dose intensification were recorded for patients with inadequate or loss of response after 12 months. Continuous variables were reported using descriptive statistics, and predictors of clinical remission were identified using logistic regression. Results A total of 37 patients treated with risankizumab were included in the analysis of which 35.1% were AT naive, and 64.9% had prior AT exposure. The median age was 33 years (IQR 26-42) and the median follow-up was 7.5 months (IQR 4.5-16.5). AT-naive patients initiated risankizumab at a median of 31 days from diagnosis (IQR 31-61). Post-induction clinical remission was achieved in 43.2% (16/37), with higher remission observed in AT-naive patients (53.8%) compared to AT-exposed patients (37.5%). Clinical response during induction was observed in 89.2% of the total cohort, with 92.3% response in the AT-naive group and 87.5% in the AT-exposed group. Of the patients with a follow up period of &amp;gt;12 months, clinical remission and response was achieved in 60% (9/15) and 93.3% (14/15) of the total cohort respectively. Endoscopic response was achieved in 81.8% (9/11) of patients undergoing colonoscopy between 8 and 12 months. Prior AT exposure significantly reduced the odds of achieving clinical remission (p&amp;lt;0.05). Age, perianal disease, baseline Hb, albumin, CRP, CDAI, SES-CD, and prior ustekinumab exposure did not affect odds of remission. Response was re-captured in 4/6 patients with secondary loss of response following 4-weekly dose intensification. No adverse events were observed during the follow-up period. Conclusion Risankizumab was highly effective for Crohn’s disease in an Emirati cohort, especially in AT-naive patients with a short time from diagnosis to treatment. High endoscopic response was noted, and dose intensification frequently restored response in patients with a secondary loss. Prior advanced therapy exposure correlated with lower remission rates, highlighting the importance of early targeted intervention.

P0609 Real-world short and long-term effectiveness of risankizumab in refractory Crohn’s disease: RISANCROHN study from the ENEIDA Registry

Abstract Background Phase III trials have demonstrated the efficacy of risankizumab (RZB), this being the first humanized monoclonal IgG1 antibody which targets the interleukin 23 p19 subunit, in Crohn’s disease (CD). However, real-world data with this drug is limited. The aim of our study was to assess the real-world effectiveness of RZB in patients with CD. Methods Adult CD patients that had received treatment with RZB in the ENEIDA registry —a large prospectively maintained Spanish database promoted by the Spanish Working Group of Crohn’s and Colitis (GETECCU)— were included. Clinical and demographical data including number of previous biologics and advanced therapies were included. The primary endpoints were steroid-free clinical remission (SFCR) after induction period (Harvey-Bradshaw score &amp;lt;5) and long-term SFCR at the end of follow-up. Influence of previous use of ustekinumab (UST) and number of previous advanced therapies in short- and long-term efficacy was also evaluated. Statistical analysis was performed using the Chi-square/Student-t test and multivariate analysis with logistic regression. Results 857 CD patients (60% male) were included: median age 50 (18-84) years, median disease duration 14 years, 27% smokers. 50% were L1, 8% L2, 38% L3, and 4% exclusively L4. B1 phenotype was present in 42%, 37% B2, 21% B3. Perianal disease was present in 28%, 46% had previously CD-related surgery and 39% extraintestinal manifestations. Only 3% were biological naïve, 50% had been exposed to 1-2 advanced therapies, and 47% to 3 or more. Following induction 56% of the patients achieved SFCR. Remission was more frequent in patients who had not previously been treated with UST (64% vs. 53% in those previously exposed to UST, p&amp;lt;0.01). In the multivariate analysis, a higher number of prior advanced therapies was associated with lower remission rates (p&amp;lt;0.01). Long-term efficacy was evaluated in 652 patients (median follow-up 7 months). At the end of the follow-up 61.2% of patients maintained SFCR. Long-term remission rate in patients non-exposed to UST was 72%, and 55% exposed to UST (p&amp;lt;0.01). In the multivariate analysis, younger age was associated with higher long-term remission rates (p&amp;lt;0.01). 11% needed dose optimization/reinduction during follow-up. 68 patients (7.9%) presented adverse events but only 18 (2%) needed to give up the treatment. Conclusion This study represents the largest cohort of real-world data on RZB in CD, including highly refractory patients with multiple prior drug failures. RZB induced SFCR in 56% of patients after induction and 61% in the long term. Higher remission rates were observed in patients who had never been exposed to UST. Younger age and fewer previous advanced therapies were associated with better outcomes.

P0913 Characteristics of patients with very late-onset ulcerative colitis: A single-center retrospective study

Abstract Background Very late-onset ulcerative colitis (UC) has become prevalent in recent years. The differences between very late-onset, late-onset, and early-onset ulcerative colitis have not yet been studied. Methods The clinical characteristics, steroid side effects, remission rates, and surgical rates of UC patients were retrospectively studied. Patients were allocated to three groups according to age at diagnosis: very late-onset group (≥ 65 years), late-onset group (50–64 years) and early-onset group (≤ 49 years). Surgery rates, within 1-2 years of diagnosis, were examined in terms of number of cases. Results Clinical characteristics such as admission age, duration of disease, history of cancer, days to diagnosis, clinical activity on admission, hemoglobin level on admission, and steroid use were significantly different between the three groups. The adverse effects of steroids were significantly more common in the very late-onset group. The remission induction rate differed significantly between the three groups: early onset, 390 (83.6%); late onset, 84 (71.7%); very late onset, 22 (67.7%). Significant differences were found in surgery rates within 1-2 years of diagnosis: surgery rates within 1 year of diagnosis, early-onset: 10 cases (3.5%), late-onset: 2 cases (3.4%), very late-onset: 3 cases (14.2%). Surgery rate 2 years after diagnosis, early-onset: 12 cases (4.2%), late-onset: 6 cases (10.3%), very late-onset: 5 cases (23.8%) (P &amp;lt; 0.05) (Figuer1). Conclusion In this study, there were no significant differences in the use of non-steroidal medications among the three groups. Our findings indicate that an older age of onset of UC is associated with more steroid side effects, lower remission rates, and a higher rate of surgery within 1–2 years of diagnosis, suggesting that very late-onset UC is more refractory than early-onset UC. We hypothesize that age-related immune changes may explain this finding.

Veterans' experiences of somatic experiencing and prolonged exposure therapies for post-traumatic stress disorder: A qualitative analysis.

Despite the proliferation of research into evidence based treatment for military PTSD there is little evidence for treatment assignment criterion and military based PTSD still demonstrates low remission rates. Thirty participants in a randomized control trial comparing Prolonged Exposure (PE) and Somatic Experiencing (SE) were interviewed on their experiences in therapy and their responses assessed using a descriptive phenomenological analysis approach to delineate the central tenets of the two therapeutic approaches. Results indicated that participants from both therapies covered themes of the experience of change, the experience of the therapeutic relationship and the therapeutic process. Within these themes, SE and PE participants reported both similar experiences, such as the predominance of physiological or bodily experiences and also described nuanced differences, specifically pertaining to therapy characteristics. SE participants described the process in terms of learning a language, applicable to alternative scenarios and PE participants described the process in terms of conquering exposures in order to achieve respite from symptoms. The current findings have relevance in terms of presenting the key elements of the distinct trauma therapies and determining treatment appropriateness based on desired outcomes. They highlight the commonalities and differences between the patient experience in PE and SE, specifically the relevance of the bodily response, treatment expertise and therapist characteristics in both treatments. Understanding the unique elements of PE, a gold-standard PTSD treatment and SE, a novel somatic-based psychotherapy, will allow for better treatment preparation for participants and potentially aid treatment assignment.

Angioedema due to acquired C1-inhibitor deficiency without hematological condition: a multicenter French cohort study of 34 patients.

Angioedema (AE) due to acquired C1-inhibitor deficiency (AAE-C1-INH) is a rare disease associating recurrent edema of mucosa and skin. Several underlying diseases have been reported, mainly lymphoproliferative diseases and monoclonal gammopathy. However, 15 to 20% of patients never exhibit such a hematological condition. To analyze specific features of patients with AAE-C1-INH without hematological condition METHODS: A multicenter retrospective cohort study of patients with AAE-C1-INH without hematological condition included from January 1999 to May 2024 in the French national CREAK registry; the clinical and biological characteristics of patients were detailed, then compared to patients with AAE-C1-INH associated with lymphoid hemopathies or monoclonal gammopathy. Thirty-four patients were included. All patients displayed a functional C1-INH below 50% of the reference value; 26 (76%) also had a decreased C1-INH antigen level; 26 (76%) displayed anti-C1-INH antibodies. After a median follow-up of 65 months, 4 (12%) patients were in spontaneous complete remission of angioedema; 15 (44%) were in complete response under long-term prophylactic treatment. Comparatively to 75 patients with lymphoma associated-AAE-C1-INH, patients with AAE-C1-INH without hematological condition displayed a higher incidence of anti-C1-INH antibodies and received more frequently symptomatic or prophylactic treatment with a lower remission rate at last follow-up. Clinical and biological features of AAE-C1-INH without hematological condition patients were similar to those of 30 monoclonal gammopathy associated-AAE-C1-INH patients. AAE-C1-INH without hematological condition display a different clinical and biological presentation from lymphoma associated-AAE-C1-INH. No autoimmune disease was identified. Unlike rituximab, long-term prophylaxis seems to prevent angioedema attacks among these patients.

Pediatric Graves’ disease in Argentina: analyzing treatment strategies and outcomes

Abstract Objectives Graves’ disease is the leading cause of hyperthyroidism in children. Only a small percentage of pediatric patients achieve remission with anti-thyroid drug treatment (ATD), and both definitive therapies (thyroidectomy, or radioiodine thyroid ablation) cause lifelong hypothyroidism. Our objective was to evaluate the outcome of patients with pediatric Graves’ disease (PGD), treated at a single tertiary center, focusing on response to medical treatment, remission rate, adverse reactions (AR), definitive treatment (DT), and potential predictive factors for remission. Methods Data from clinical charts of 130 patients diagnosed with PGD between 2006 and 2021 were collected: epidemiological, clinical, biochemical characteristics, outcome, remission, adverse reactions (AR), and DT were registered. Predictive factors at diagnosis were evaluated for 88 patients diagnosed at our center. Results Our patients were 78 % female, 98 % Hispanic, with a median age of 12.7 years (range 1.7–17.3 years). Fourteen (11 %) had Down syndrome. Severe thyrotoxicosis (FT4&gt;5.5 ng/dL) was seen at diagnosis in 66 %. Initially, 129/130 received ATD; during the study, 17 participants (13 %) reached remission, with a median ATD duration of 3.1 years (range 1.3–6.1 years). The chance of remaining hyperthyroid was 65 %. Only one patient relapsed 1.3 years post-ATD. Forty-six percent (59/129) needed DT, 31 % (40/129) were lost to follow-up, and 10 % (11/129) remained on ATD. AR affected 26 % of the patients and most (74 %) occurred within the first 3 months, half of them severe enough to discontinue ATD. No significant predictive factors were identified. Results ATD, our first-line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD. Conclusions ATD, our first line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD.

Invasion of the Cavernous Sinus Medial Wall by Pituitary Adenomas: Intraoperative Evaluation and the Clinical Efficacy of the Cavernous Sinus Medial Wall Resection in the Treatment of Somatotroph Adenomas.

Pituitary adenomas are common benign intracranial tumors. This study aimed to explore the relevant factors influencing the cavernous sinus medial wall invasion by Pituitary adenomas based on intraoperative evaluation. Meanwhile, the authors introduced a safe technique for the resection of the medial wall of the cavernous sinus and conducted a preliminary evaluation of the efficacy of this technique. The clinical data of 108 patients with pituitary adenomas who underwent surgery at our institution were collected. Binary logistic regression analysis was utilized to identify independent predictors of medial wall invasion. Furthermore, the authors performed medial wall resection on 12 cases of somatotroph adenomas with medial wall invasion to initially assess the surgical efficacy of this technique for somatotroph adenomas. Multivariate Logistic regression analysis showed that tumor Knosp grade and somatotroph adenomas were independent predictors of medial wall invasion (P<0.05). For somatotroph adenomas, medial wall resection resulted in a high biochemical remission rate (83%), and all patients were free of recurrence at the last follow-up. Higher knosp grade and somatotroph adenomas will increase the risk of medial wall invasion of the cavernous sinus. Relying solely on the Knosp grade system to evaluate tumor invasion of the medial wall without differentiating between tumor subtypes is inaccurate. Invasion of the medial wall may be a cause of low biochemical remission rates and recurrence after surgery for somatotroph adenomas. The technique of medial wall resection is safe and effective, and holds significant importance in the treatment of somatotroph adenomas.

Crescents as Independent Risk Factor in the Progression of Primary Membranous Nephropathy.

The role of crescent formation in primary membranous nephropathy (PMN) and its potential impact on prognosis remain an area of ongoing investigation. This study stratifies patients with PMN into two cohorts: one with crescents and one without. It then compares these groups to investigate the influence of crescents on the prognosis of PMN. In this retrospective analysis, we included patients who had a confirmed diagnosis of PMN and exhibited crescents upon renal biopsy. The study population was sourced from the medical records at the Affiliated Hospital of Guangdong Medical University in Zhanjiang, China, spanning from January 2017 to June 2023. To enable a comparative analysis of clinical, pathological, and prognostic features, a control group was established, comprising 106 patients diagnosed with PMN who did not have crescent formation. These controls were randomly selected from the same time frame. Regular follow-up of the patients continued in the outpatient setting for at least six months. A total of 53 patients with PMN and crescent formation were included in this study, while 106 individuals without crescents served as a randomly selected control group. Patients with PMN and crescents exhibited higher systolic blood pressure (P = 0.015), 24-hour proteinuria (P = 0.006), serum creatinine (P = 0.029) levels, and lower glomerular filtration rate (P = 0.002), compared to those without crescents. Histological examination revealed a higher proportion of focal segmental sclerosis (P < 0.001), spherical sclerosis (P < 0.001), arteriosclerosis (P = 0.02), and interstitial fibrosis with tubular necrosis (P = 0.002) in patients with PMN and crescent formation. Immunofluorescence staining demonstrated a weaker IgG4 fluorescence intensity in patients with PMN and crescent formation. At the end of the follow-up period, patients with PMN and crescents had a lower remission rate (P = 0.022), poorer renal function (P = 0.007), and lower albumin (P = 0.039) levels. Kaplan-Meier (KM) analysis identified proteinuria and crescent formation as independent risk factors for adverse outcomes in patients with PMN (P < 0.001 and P < 0.05). Immunohistochemistry staining revealed positive expression of CD68 and CD20 in the renal interstitium of patients with PMN, regardless of the presence of crescents. Crescent formation is associated with a risk of adverse outcomes in patients with PMN. Patients with crescents exhibit severe clinical and pathological features and have poorer prognoses.

Metabolic and hepatic phenotypes in sarcopenic obesity and impact of bariatric surgery

Background & AimsSarcopenic obesity (SO) is associated with cardiometabolic disorders and steatotic liver disease and carries major health risks. We assessed the hepatic and metabolic clinical phenotype associated with SO in patients with obesity undergoing bariatric surgery (BS). We also evaluated whether weight-loss and metabolic improvement post-surgery differ between patients with and without SO. Methods972 consecutive patients from a single-center BS cohort who underwent whole-body dual-energy X-ray absorptiometry (DXA) and peri-operative liver biopsy were included. SO was diagnosed using the AIM-SO score, an AI-assisted unbiased clustering algorithm based on body composition. One-year post-surgery, 862 patients were reassessed for AIM-SO score changes. ResultsPre-operatively, 207 (21.3%) patients were diagnosed with SO. These patients had significantly higher prevalence of type-2 diabetes (T2D), arterial hypertension and obstructive sleep apnea (OSA) compared to patients without SO (all p≤0.003). Patients with SO had more severe liver damage: higher grades of moderate/advanced steatosis (64.2% vs. 47.3%), steatohepatitis (44.4% vs. 32.3%) and advanced fibrosis (12.1% vs. 6.0%) (all p≤0.01). One-year post-BS, 58.5% of patients had remission of SO. Patients with persistent SO exhibited less weight-loss than those with SO remission (–23.8 kg vs. –29.1 kg, p<0.001) and had lower rates of remission for T2D (41.9% vs. 69.8%), arterial hypertension (20.8% vs. 45.3%), and metabolic syndrome (47.6% vs. 75.0%) (all p≤0.009). ConclusionThe DXA-based AIM-SO score identifies patients with SO who are at greater risk of hepatic and cardiometabolic comorbidities, and predicts less favorable weight-loss and metabolic improvements post-BS.

Childhood acute lymphoblastic leukemia with CREBBP gene mutation: a clinical analysis of 14 cases

To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. The ALL patients with CREBBP gene mutation accounted for 1.5% (14/963) among all children diagnosed with ALL during the same period of time, among whom there were 4 boys (29%) and 10 girls (71%), with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS, KRAS, ETV6, FLT3, PAX5, SH2B3, CDKN2A, and CDKN2B, and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen, with a complete remission (CR) rate of 79% (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone, with a recurrence rate of 21% (3/14), among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children, 1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92%±7%, and the event-free survival rate was 73%±13%. ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate, and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Glutamatergic Modulators for Major Depression from Theory to Clinical Use.

Major depressive disorder (MDD) is a chronic, burdensome, highly prevalent disease that is characterized by depressed mood and anhedonia. MDD is especially burdensome as approved monoamine antidepressant treatments have weeks-long delays before clinical benefit and low remission rates. In the past 2decades, a promising target emerged to improve patient outcomes in depression treatment: glutamatergic signaling. This narrative review provides a high-level overview of glutamate signaling in synaptogenesis and neural plasticity and the implications of glutamate dysregulation in depression. Based on this preclinical evidence implicating glutamate in depression and the rapid improvement of depression with ketamine treatment in a proof-of-concept trial, a range of N-methyl-D-aspartate (NMDA)-targeted therapies have been investigated. While an array of treatments has been investigated in registered phase 2 or 3 clinical trials, the development of most of these agents has been discontinued. Multiple glutamate-targeted antidepressants are actively in development, and two are approved. Nasal administration of esketamine (Spravato®) was approved by the US Food and Drug Administration (FDA) in 2019 to treat adults with treatment-resistant depression and in 2020 for adults with MDD with acute suicidal ideation or behavior. Oral combination dextromethorphan-bupropion (AXS-05, Auvelity® extended-release tablet) was FDA approved in 2022 for the treatment of MDD in adults. These approvals bolster the importance of glutamate in depression and represent an exciting breakthrough in contemporary psychiatry, providing new avenues of treatment for patients as first-line therapy or with either poor response or unacceptable side effects to monoaminergic antidepressants.

Endoscopic morphology of gastric MALT lymphoma correlate with API2/MALT1 fusion and predict treatment response after helicobacter pylori eradication

BackgroundThe presence of API2/MALT1 fusion in gastric mucosa-associated lymphoid tissue (MALT) lymphoma predicts poor response to Helicobacter pylori (Hp) eradication therapy. This study aimed to assess the correlation between endoscopic morphology of MALT lymphoma and API2/MALT1 fusion and evaluate treatment response to Hp eradication based on morphological subtypes.MethodsA retrospective review was conducted on patients diagnosed with gastric MALT lymphoma between January 2011 and December 2022. Endoscopic morphology was categorized as superficial, non-superficial, or mixed type. The superficial type was further classified into gastritis superficial lesion and localized superficial lesion based on border clarity. Logistic regression models evaluated the impact of clinical and endoscopic characteristics on anti-Hp therapy effectiveness.ResultsAmong the 114 patients included, 93 (81.6%) were Hp-positive, and API2/MALT1 fusion was detected in 58 (50.9%) cases, The superficial type was the predominate morphology (73/114, 64%). The regular arrangement of collecting venules (RAC) sign was noted in 21 (18.4%) cases. In superficial subtypes, the RAC signs were more frequently observed in localized lesion than gastritis lesion (35.6% vs. 7.1%, p = 0.01). and the superficial localized lesion was more common in individuals with positive API/MALT1 fusion than negative ones (76.9% vs. 44.1%, p = 0.01). Following Hp eradication, the remission rate for localized lesion was 34.3%, significantly lower than for gastritis lesion (66.7%, p = 0.01). Both endoscopic morphology (OR = 0.26, 95% CI 0.09–0.75) and API2-MALT1 fusion (OR = 14.29, 95% CI 4.19–48.67) impacted the efficacy of anti-Hp therapy. However, multivariate analysis identified API2-MALT1 fusion as the only independent predictor of treatment outcome (OR = 12.18, 95% CI 3.49–42.55, p < 0.001).ConclusionGastric MALT lymphomas with superficial-type morphology, particularly those with defined borders resembling early gastric cancer, were associated with API2/MALT1 fusion and a lower remission rate after Hp eradication therapy. This suggests that endoscopic morphology, along with API2/MALT1 fusion status, could help predict the therapeutic response, with API2/MALT1 fusion serving as a critical indicator of treatment resistance.

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Genetic factors influence the effect of its main treatment option, antidepressant drugs (ATD). The GRIK4 rs1954787(T>C) genetic polymorphism was associated with response following 1-3 months of ATD treatment in some studies, but not others. We aimed to analyze its association with clinical outcomes in a cohort of 6-month ATD-treated patients and meta-analysis. Clinical data were obtained at baseline and after 1 (M1), 3 (M3), and 6 (M6) months of ATD treatment in 390 patients of the METADAP cohort. Mixed-effects models were used to assess the association of the GRIK4 rs1954787 polymorphism with the Hamilton Depression Rating Scale (HDRS) score and response and remission rates across time. Meta-analyses of ATD treatment response were performed with previously meta-analyzed data and METADAP. Compared to C allele carriers at M3 (n = 200), TT homozygotes at M3 (n = 66) had higher HDRS scores (coef = 3.37, 95% CI [1.30-5.54], Padj = 0.0046) and lower remission rates (OR = 0.36, 95% CI [0.16-0.76], Padj = 0.029). At M6, greater differences between TT homozygotes (n = 53) and C allele carriers (n = 152) were observed for HDRS scores (coef = 4.68, 95% CI [2.17-7.18], Padj = 0.00091) and remission rates (OR = 0.26, 95% CI [0.12-0.54], Padj = 0.0016). Meta-analyses of response were significant when comparing C vs T alleles (OR = 1.31, 95% CI [1.06-1.62], P = 0.014) and CC vs TT genotypes (OR = 1.63, 95% CI [1.10-2.38], P = 0.019). Altogether, our results support an association of the GRIK4 rs1954787(T>C) polymorphism with clinical improvement following ATD treatment. This association should be further assessed in other longitudinal studies. Its position within the glutamatergic system may help in understanding the mechanism of ATD action.

Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial

Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36–15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31–0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.

The Potential Role of Polyphenol Supplementation in Preventing and Managing Depression: A Review of Current Research

Depression is a common mental illness that affects 5% of the adult population globally. The most common symptoms of depression are low mood, lack of pleasure from different activities, poor concentration, and reduced energy levels for an extended period, and it affects the emotions, behaviors, and overall well-being of an individual. The complex pathophysiology of depression presents challenges for current therapeutic options involving a biopsychosocial treatment plan. These treatments may have a delayed onset, low remission and response rates, and undesirable side effects. Researchers in nutrition and food science are increasingly addressing depression, which is a significant public health concern due to the association of depression with the increased incidence of cardiovascular diseases and premature mortality. Polyphenols present in our diet may significantly impact the prevention and treatment of depression. The primary mechanisms include reducing inflammation and oxidative stress, regulating monoamine neurotransmitter levels, and modulating the microbiota–gut–brain axis and hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis. This review summarizes recent advances in understanding the effects of dietary polyphenols on depression and explores the underlying mechanisms of these effects for the benefit of human health. It also highlights studies that are looking at clinical trials to help future researchers incorporate these substances into functional diets, nutritional supplements, or adjunctive therapy to prevent and treat depression.

An overview of major depression disorder: The endocannabinoid system as a potential target for therapy.

Major depressive disorder is the psychiatric disease with the highest global prevalence, impacting social functioning and decreasing the quality of life. The partial pathophysiological knowledge of the disease, the economic burden and the low remission rates are sufficient justification to carry out an update on the subject in the search for new therapeutic approaches and targets. The endocannabinoid system has been linked to the development of depression, and its stimulation or antagonism is a promising approach in the treatment of major depressive disorder. Cannabidiol (CBD) and its properties have been widely studied recently; its analgesic, anti-inflammatory, antineoplastic and neuroprotective roles have even been reported in animal models and clinical trials, achieving its approved use for certain neurodegenerative pathologies. The use of CBD in depression biomodels and clinical trials has not been the exception, and here we contrast the current evidence of its administration and pharmacology against the pathological mechanisms of major depressive disorder.

7081 A Spotlight on Marine Lenhart Syndrome

Abstract Disclosure: R. Alshantti: None. A.M. San Hernandez: None. J. Wu: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Marine-Lenhart Syndrome is a rare condition with a prevalence of 0.8-4.1% of cases with Graves’ disease. It is defined by the coexistence of Graves’ disease and autonomously functioning thyroid nodule(s). It is an under-recognized cause of hyperthyroidism. A limited number of cases have been reported in the literature. We report an interesting case of Marine-Lenhart Syndrome characterized by the presence of elevated thyroid stimulating immunoglobulins (TSI) and an autonomous right thyroid nodule. Case Description: A 37-year-old man with a history of hyperthyroidism from Graves’ disease and a right thyroid nodule was referred to endocrinology clinic. He was diagnosed with hyperthyroidism in 2015 at an outside facility. He had elevated thyroid stimulating immunoglobulins (TSI) and a 2.9 cm right thyroid nodule which was biopsied and had benign cytopathology. Hyperthyroidism was treated with methimazole (MMI) but without subsequent remission of Graves’ disease. He ran out of MMI and re-presented with symptomatic hyperthyroidism with fatigue, tremors, and hyperdefecation. There was no ocular involvement or thyroid compressive symptoms. Biochemical work up was consistent with uncontrolled hyperthyroidism (suppressed TSH 0.01 uIU/mL [Ref range: 0.45-5.33], and elevated FT4 2.58 ng/dl [Ref range: 0.70-2.20], elevated free T3 8.7 pg/ml [Ref range: 2.5-3.9], and mildly elevated TSI 0.72 IU/L [Ref range: 0.54 or less]. MMI was therefore reinitiated. Thyroid Uptake scan demonstrated an increased focal 24-hour Iodine-131 uptake of 57% in the right lobe with suppression of the left lobe. Thyroid ultrasound support the finding of large right thyroid nodule (2.3 x 2.4 x 3.9 cm) with diffuse heterogeneous thyroid. The presence of TSI, lack of control of hyperthyroidism for more than 2 years of treatment, and presence of a functioning thyroid nodule raise the suspicion of Marine-Lenhart Syndrome. Indeed, the findings of an autonomously functioning right thyroid nodule with concomitant Graves’ disease establish the diagnosis of Marine-Lenhart Syndrome. The option of RAI ablation vs total thyroidectomy was discussed with the patient. The patient opted for thyroidectomy. Conclusion: Based on studies, approximately 35% of patients with Graves’ disease have thyroid nodule(s) and only 2.7% are functioning adenomas. The combination of positive TSI or TrAb and functioning thyroid nodules has been termed Marine-Lenhart syndrome. The syndrome was named after David Marine and Carl Lenhart who initially described it in 1911. Unlike Graves’ disease, patients with Marine-Lenhart Syndrome have a lower remission rate with thioamides, require definitive treatment with RAI ablation at a high dose or total thyroidectomy, and may easily be misdiagnosed by many endocrinologists. Presentation: 6/2/2024

12342 Retrospective Multicenter Study Of Prolactinomas In Men

Abstract Disclosure: M.A. Guitelman: None. G. Cardenas: None. A. Rogozinski: None. C. Ballarino: None. M.F. Battistone: None. K. Danilowicz: None. S. Diez: None. P. Fainstein-Day: None. A. Furioso: None. V. Garcia Roel: None. M.S. Gonzalez Pernas: None. D.A. Katz: None. M.G. Loto: None. S. Mallea Gil: None. M.P. Manavela: None. M.S. Martinez: None. K.A. Miragaya: None. P. Slavinsky: None. S. Sosa: None. J. Tkatch: None. G. Tubert: None. M. Vitale: None. M. Glerean: None. Prolactinomas in men: a retrospective multicenter study Introduction and Objectives: prolactinomas in men have recently been included by the World Health Organization as a more aggressive tumor category due to their size, invasiveness and response to treatment. Our objective was to evaluate clinical, biochemical, and imaging characteristics, therapeutic response, and long-term evolution (outcome) of a cohort of men with prolactinoma. Patients and Methods: multicenter retrospective study including 311 men with prolactinoma. Initial clinical parameters, therapeutic modalities, PRL normalization rate and gonadal recovery, as well as tumor reduction were analyzed. The results were expressed as median (min-max range). Results: 35 micro (Mi) and 276 macroadenomas (Ma) were found (199 invasive, 71 Giant ≥4 cm). The median age at diagnosis was 41 (13-84) and 40 y-old (15-73) for micro and macro respectively. The most frequent reasons for consultation were symptoms of hypogonadism in patients with Mi, while visual disturbances, headache, and incidental findings were seen in patients with Ma. Apoplexy as presentation was observed in two patients with Ma. Hypogonadotrophic hypogonadism was present in 90 % of patients in whole cohort. Median basal PRL was 144 in Mi and 1633 ng/ml in Ma. Treatment with cabergoline (CAB) was indicated in all but one patient with Ma who remitted after surgery. Normalization of PRL was achieved in 85.7% and 65.7% of Mi and Ma respectively. The median follow-up time was 48 months (6-240). Sixty-three Ma and only one Mi were submitted to surgery, 2 patients achieved remission criteria (Mi/Ma); a patient with micro experienced recurrence after 3 years, the remaining patients continued or started CAB after surgery. Ki-67 ≥3% was reported in 17/46 available pathologies. The maximum dose of CAB was 4.5 and 12 mg/wk , with a median of 0.5 and 1.5 mg/wk for Mi and Ma, respectively. Resistance to CAB (dose ≥3mg/week) occurred in 5.7% Mi and 35.4% Ma. Gonadal function recovery without testosterone requirement was achieved in 80% of Mi and 63% of Ma. Tumor remnant was observed in 34% and 49% of Mi and Ma respectively Ten patients with Ma received radiotherapy. Five patients presented CSF fistula during treatment with CAB, and another 3 impulse control disorder. One patient with carcinomatous transformation was treated with temozolomide. Conclusions: In our series of 311 men with prolactinomas, majority Ma consulted for neuro-ophthalmological symptoms, while hypogonadism was the most frequent initial symptom in Mi, despite the fact that 90% of the total population showed it at presentation. Giant, invasive and proliferative tumor were highly prevalent in Ma. Pharmacological treatment continues to be the first line of choice, with a high rate of normalization of PRL and recovery of gonadal function, but a low rate of long-term remission. Presentation: 6/2/2024

Placebo rates in Crohn’s disease randomized clinical trials: An individual patient data meta-analysis

Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials. We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates. Analysis of individual patient data from 8 induction (n= 1147) and 4 maintenance (n= 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%-32%) and 10% (95% CI, 8%-14%), respectively, and 32% (95% CI, 23%-42%) and 22% (95% CI, 14%-33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%-35%) and 11% (95% CI, 8%-15%) respectively, and 26% (95% CI, 20%-33%) and 10% (95% CI, 8%-14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%-48%) and 32% (95% CI, 24%-40%), respectively, and 29% (95% CI, 24%-34%) and 16% (95% CI, 13%-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance. Patient- and trial-level characteristics influence placebo rates in Crohn's disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.