Biochemical Remission Research Articles

Postoperative outcome of special primary aldosteronism undergoing surgery based on adrenal vein sampling results

To further demonstrate the gold standard role of adrenal vein sampling (AVS) in the subtyping diagnosis of primary aldosteronism (PA). In this study, 9 patients with special PA, whose functional advantages indicated by AVS were contrary to the results of CT examination, were selected. Laparoscopic adrenalectomy was performed based on AVS results, and the surgical outcome was followed up. Nine patients, aged[M(Q1, Q3)] 58.0 (52.0, 63.0) years, including 7 males and 2 females, were followed up for 12 (9, 12) months. CT revealed unilateral morphological abnormalities in 5 cases (the functional advantage side indicated by AVS was contrary to the results of CT examination), and bilateral abnormalities in 4 cases (AVS results confirmed unilateral abnormalities). During the follow-up, all 9 patients achieved complete biochemical remission, 4 patients achieved complete clinical remission, and 5 patients achieved partial clinical remission. The study indicates that compared with CT imaging, AVS has better accuracy in PA subtyping, and selecting surgical side based on AVS results is a reliable and effective strategy.

Upadacitinib in patients with difficult-to treat Crohn’s disease

Abstract Background Upadacitinib has been approved to treat adults with moderate-to-severe Crohn’s disease (CD). Only a few studies have evaluated the effectiveness and safety of the drug in clinical practice, with even fewer focusing on patients with difficult-to-treat CD. Therefore, this study assessed the effectiveness and safety of upadacitinib in CD patients for whom all other available therapies had failed. Methods Patients with moderate-to-severe CD who had received upadacitinib after exhausting other treatments were included. The primary endpoint was corticosteroid-free clinical remission. Secondary endpoints included clinical response, biochemical remission, transmural response, transmural healing, deep remission, and continuation of therapy. Results The study included 64 CD patients. After 12 weeks, 51.6% of patients achieved steroid-free clinical remission, and 71.8% showed a clinical response. Biochemical remission was observed in 36.2% of patients, and transmural healing in 28.8%. At 24 weeks, clinical remission was achieved in 78% of patients continuing therapy. Therapy was discontinued before the end of the induction period in 14 patients (21.9%) due to therapy failure or adverse events. Conclusions This study highlights the efficacy of upadacitinib in CD patients for whom multiple drugs have failed, providing real-world evidence supporting its use in patients with moderate-to-severe CD unresponsive to other therapies.

The value of ultrasound for monitoring disease activity in giant cell arteritis

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in the elderly. Although the diagnosis of GCA has improved, monitoring its disease activity remains challenging due to the lack of validated tools and biomarkers. The current reliance on assessing symptoms, physical signs, and inflammatory markers during disease follow-up presents limitations, notably the nonspecific nature of GCA-related symptoms and the suppressive impact of IL-6 inhibitors on inflammatory markers. Therefore, recent attention has shifted toward acknowledging imaging as a monitoring tool, particularly ultrasound, given its widespread accessibility, cost-effectiveness, and well-established role in GCA diagnosis. Research on this topic has found that ultrasound characteristics, including the number of affected arterial segments and halo size, are associated with laboratory markers and treatment response, underscoring the ultrasound’s potential as a monitoring tool for GCA. It has also been demonstrated that ultrasound abnormalities progress differently throughout the disease course, depending on the type of arterial involvement, with vessel wall changes in the axillary arteries resolving more slowly than those in the temporal arteries. Nevertheless, there are still no studies comparing the added value of regular ultrasounds for monitoring disease activity to clinical and laboratory monitoring alone; hence, this imaging modality is not yet recommended for patients with GCA in clinical and biochemical remission. This narrative review aims to synthesize the main research findings of key studies addressing the role of ultrasound for monitoring disease activity in GCA, with a focus on the pattern of arterial involvement. It highlights the potential of ultrasound, particularly halo sign assessment, for evaluating disease progression but notes that further validation and standardization of protocols are needed to improve accuracy and enable routine use.

Optimal timeframe for achieving biochemical remission in Crohn's disease patients treated with first-line biologics: A retrospective multicenter study.

Predicting treatment response in Crohn's disease (CD) patients initiating biological therapy is crucial. The first step involves considering symptom control and normalization of C-reactive protein (CRP). However, data on the actual rates of achieving CRP normalization and the appropriate timeframe are lacking. Therefore, we aim to investigate the rate of attaining CRP normalization and identify its optimal timeframe in CD patients initiating biological therapy. In this retrospective multi-center study, we analyzed moderate to severe CD patients initiating biological therapy from January 2012 to July 2023. The primary outcome was the rate and timeframe for achieving CRP normalization. Secondary outcomes included clinical outcomes in patients who achieved CRP normalization and factors associated with early CRP normalization. Of 183 patients, 123 (67.2%) achieved CRP normalization, with a median duration of 3.8 months (interquartile range 1.4 to 7.4 months). The duration and value difference for CRP normalization between anti-tumor necrosis factor agents, ustekinumab, and vedolizumab were statistically insignificant. Cumulative rates of CD-related hospitalization, intestinal resection, and drug discontinuation over 8 years were 11.4%, 2.4%, and 12.2%, respectively. The duration of CRP normalization correlates with drug discontinuation (area under the curve: 0.64). Treatment with 5-aminosalicylic acid (HR 2.77; 95% confidence interval [CI] 1.26-6.11) and high albumin level (HR 1.64, 95% CI 1.04-2.61) favored early CRP normalization, whereas structuring behavior less likely than inflammatory behavior (HR 0.43, 95% CI 0.19-0.96). We have provided the actual rate of achieving CRP normalization and its appropriate timeframe as an initial target in CD treatment.

Long-term retreatment outcomes after definitive management of Graves’ disease with radioactive iodine versus surgery

BackgroundCommon treatments for Graves’ disease include antithyroid drugs (ATD), radioactive iodine (RAI), and surgery. RAI avoids surgical morbidity, but rate and durability of remission varies across studies. This study directly compared the long-term results of Graves’ disease treated by surgery versus RAI and hypothesized that RAI would be associated with lower rates of long-term biochemical remission and higher likelihood of retreatment. MethodsThis retrospective cohort study included individuals diagnosed with Graves’ disease who were treated surgically, with RAI, or both at a tertiary referral center. Definitive retreatment was defined as additional RAI or surgery after index treatment, and retreatment was defined as requiring ATD or a second definitive treatment after index treatment. Remission was defined by normalization of thyroid stimulating hormone without retreatment at 6 months. ResultsIndex definitive therapy was total thyroidectomy for 72 patients and RAI for 104 patients. The median follow-up time was 3.6 years. The rate of remission at 6 months in the RAI group (68.8%) was lower than that in the surgery group (98.6%) (odds ratio: 0.03, P < .001). Patients who underwent index RAI experienced a significantly higher cumulative incidence of any retreatment at all time points than those who underwent index surgery (P < .001). Among RAI patients who achieved euthyroidism within 6 months, 19% developed subsequent relapse requiring ATD therapy or retreatment. ConclusionThe need for retreatment after index therapy for Graves’ disease is significantly lower after thyroidectomy than after RAI.

Remission of Acromegaly: The Sooner the Better.

Remission of acromegaly is defined by normalization of GH/IGF-1 values according to age and gender. While treatment strategies, biochemical cut-off to reach, and morbidities related to the persistence of the disease are well described in the literature, there is little data focusing on the delay to reach remission and its consequences. In this commentary, the authors discussed the results obtained from the UK acromegaly registry showing that the time to biochemical remission predicts the overall survival of patients in acromegaly.

12492 Clinical Resolution Of Parkinsonism And Dementia Following Radio Frequency Ablation Of A Parathyroid Adenoma

Abstract Disclosure: P. Finny: None. T. George: None. A.K. Francis: None. Background: Parkinsonism is a rare neurological manifestation of primary hyperparathyroidism. Radiofrequency ablation (RFA) of parathyroid adenomas is a novel treatment modality. Clinical Case: A 78 year old lady presented to our Emergency department with hypercalcemic encephalopathy. She had long standing Diabetes mellitus, Bronchial asthma and Parkinsonism with dementia for the past 14 years. She was bed bound with dependence on carers for activities of daily living (ADL). She had been diagnosed elsewhere in 2018 to have primary hyperparathyroidism due to a right inferior parathyroid adenoma and had a right hemithyroidectomy with a failed parathyroidectomy. She was being managed with Cinacalcet 60 mg daily for the past 4 years. Prior to this admission she had discontinued Cinacalcet for a few days. Her initial serum calcium was 15.3 mg/dl (8.7-10.7), phosphorus 1.80 mg/dl (2.5-4.5) and PTH 451 pg/ml (15- 88). She was aggressively treated with intravenous normal saline hydration followed by Furosemide injection. Then she was given Calcitonin injections subcutaneously and IV Zoledronic acid infusion. Her calcium dropped to 11.8 mg/dl within 48 hours of admission, and her sensorium improved. Imaging studies showed no visible parathyroid adenoma on ultrasound, but the 4D CT scan of the neck revealed a left inferior parathyroid adenoma of size 1.1 x 1.2 cm. This was concordant on the Technetium 99m Sestamibi scan. Her MRI Brain showed bilateral globus pallidus calcification. In view of her multiple comorbidities making her a poor candidate for general anaesthesia, non-surgical options were considered. A percutaneous ultrasound guided RFA of the left parathyroid adenoma was successfully performed. Post procedure the PTH dropped from 321 pg/ml to 54.9 pg/ml within 24 hours. The calcium, phosphorus and PTH remained normal. Her Parkinsonism and dementia significantly improved and we could wean her off the anti- parkinsonian and anti-psychotic medication. She became ambulant and regained her cognitive functions. This clinical and biochemical remission was maintained over the next 22 months of follow up. Conclusion: RFA is a novel therapeutic option in treating parathyroid adenomas among surgically unfit patients. Reversal of advanced Parkinsonism following correction of chronic hypercalcemia led to this patient regaining a good quality of life. 4D CT scan of the neck is useful in localizing the parathyroid adenoma when there is discordance between the ultrasound and Sestamibi scan.

9363 Spontaneous Cushing Disease Remission Induced By Pituitary Apoplexy

Abstract Disclosure: J.E. Esquivel Vargas: None. F. Ruiz Salazar: None. A.B. Santos Rojo: None. Background: Spontaneous remission of Cushing disease is rare, and it is mainly due to apoplexy of a pituitary tumor. Clinical case: 14-year-old female presented with clinical features of Cushing syndrome. Initial tests were consistent with Cushing disease (CD): elevated 24h urinary cortisol (235µg/24h, n&amp;lt;90µg/24h), abnormal 1 mg dexamethasone overnight test (cortisol after 1 mg dex 3.4µg/dL, n&amp;lt;1.8µg/dL), and elevated ACTH-concentrations (83.5 pg/mL, n 10-60pg/mL). Pituitary adenoma was suspected, and the patient was referred for a transsphenoidal resection of the adenoma. While waiting for surgery the patient presented to the Emergency department with a headache and clinical signs of meningism. Computed axial tomography of the central nervous system was performed, and no structural alterations were found. The symptoms subsided with analgesia. One month later she presented again to the Emergency department with clinical findings of acute adrenal insufficiency (cortisol level of 4.06 µg/dL), and she was noted to have spontaneous biochemical remission associated with resolution of her symptoms of hypercortisolism. Nuclear magnetic resonance imaging was performed describing a 2.6 x 1.8mm hypointense pituitary lesion, suggestive of cerebrospinal fluid, which could be a remnant of a pituitary microadenoma. For that reason, spontaneous CD remission induced by pituitary apoplexy (PA) was diagnosed. The patient has been managed conservatively since the diagnosis and remains in clinical and biochemical remission until the present time after 10 months of follow up. Conclusion: There are 3 unique aspects of our case: the early age of onset of symptoms, the spontaneous remission of CD due to PA which has been rarely reported in the medical literature, and the patient presented a microadenoma because there are less than 10 clinical case reports of PA associated with microadenoma. Presentation: 6/1/2024

Experience in the Treatment of Male Prolactinomas: A Single-Center, 10-Year Retrospective Study

Introduction: Male prolactinomas are uncommon and typically macroadenomas with difficult treatment and management. The purpose of this study was to summarize the treatment and management experiences of 254 male prolactinoma patients at a single center. Methods: This was a 10-year retrospective study conducted at a single center. A total of 254 male prolactinoma patients were included. Clinical data for all subjects were collected using an electronic medical record system. Results: A total of 254 male patients with prolactinoma were studied. Their median age at onset was 28.8 years, and median disease duration was 28.5 months. The median PRL levels were 582.0 ng/mL at diagnosis. Their median maximum tumor diameter was 23.0 mm, with macroadenoma accounting for the majority (76.7%). After treatment, the biochemical remission rate with monotherapy was 36.6%, but significantly increased to 60.6% with multidisciplinary treatment (p < 0.001). Knosp 0–2 patients had significantly higher rates of biochemical remission compared to Knosp 3–4 (all p < 0.05). In addition, the maximum diameter of adenoma (B = −0.110, p = 0.008) and cavernous sinus invasion (B = −1.741, p = 0.023) were negatively correlated with postoperative biochemical remission. The maximum diameter of the adenoma (B = − 0.131, p < 0.001) was a negative correlation factor, while treatment duration (B = 0.034, p = 0.002) was a positive correlation factor for biochemical response to medication. Conclusion: Male prolactinoma has a low biochemical remission rate when treated alone, but multitherapy can improve it even more. Surgery may also be considered for male prolactinoma with a micro, and noninvasive tumor after a thorough evaluation.

Subcutaneous infliximab in Crohn’s disease patients with previous immunogenic failure of intravenous infliximab

PurposeImmunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective.MethodsIn a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn’s disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12.ResultsTwenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%).ConclusionSubcutaneous infliximab treatment of Crohn’s disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.

Comparison of ustekinumab, infliximab and combination therapy in moderately to severely active ulcerative colitis - a study protocol of a randomized, multicenter, head-to-head COMBO-UC trial.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex etiology that affects the large intestine. Characterized by chronic, bloody diarrhea, UC can lead to severe complications, including an increased risk of colorectal cancer. Despite advancements in conservative treatment, including biologics like anti-TNF agents and ustekinumab (UST), many patients do not achieve full remission. Dual targeted therapy (DTT) combining infliximab (IFX) and UST is a promising approach to improve treatment outcomes. This prospective, randomized, multicenter, head-to-head controlled trial will evaluate the efficacy and safety of UST, IFX, and combination therapy (UST + IFX) in 172 patients with moderate to severe active UC across eight gastroenterology centers in Poland. The study includes a 14-16 week remission induction period followed by a 52-week maintenance phase. Patients will be randomly assigned to one of three treatment arms: IFX monotherapy, UST monotherapy, or IFX + UST combination therapy. Primary endpoint is clinical and endoscopic remission post-induction. Secondary endpoints include clinical response, biochemical remission, histological remission, and quality of life assessments using the Inflammatory Bowel Diseases Questionnaire and 36-Item Short Form Survey. Safety will be monitored through adverse event and serious adverse event reporting. This trial aims to determine whether combining IFX and UST can achieve higher remission rates and better long-term outcomes compared to monotherapy. The results could provide crucial insights into the optimal use of biologic agents in UC treatment, potentially establishing DTT as a standard therapy. The study's design, including extensive follow-up and robust endpoint measures, will contribute to understanding the therapeutic potential and safety profile of this combination therapy.

Indicators of functional state of liver, blood lipid spectrum in patients with steatotic liver disease associated with metabolic dysfunction: modern approaches to complex treatment. Review

Objective — to study the dynamics of indicators of the functional state of the liver, the lipid spectrum of the blood, to evaluate the cardiovascular risk according to SCORE‑2 (Systematic Coronary Risk Estimation 2) scale under the influence of complex pathogenetic treatment of the detected disorders in patients with steatotic liver disease associated with metabolic dysfunction (SLDMD) in combination with obesity. Materials and methods. 46 outpatients with a diagnosis SLDMD were examined: 29 (63.1%) men and 17 (36.9%) women aged 32—55 years. The patients were divided into two groups. The main group included 19 (41.3%) persons who received atorvastatin: 20 mg/day for 90 days. The comparison group consisted of 27 (58.7%) patients who were prescribed ursodeoxycholic acid preparations in combination with atorvastatin: 250 mg (15 mg/kg of body weight) for 90 days. The control group consisted of 12 healthy persons of the appropriate age. The anthropometric criterion of obesity was the Quetelet index. Phenotypic variant of obesity was determined by the ratio of waist circumference/hip circumference (WC/HC). Among the patients of the main group, there were 9 (47.4%) persons with I degree of obesity ((32.6±2.2) kg/m2), 6 (31.5%) persons with II degree ( 35.8±3.6 kg/m2), and 4 (21.1%) persons with III degree (40.0±2.1kg/m2), in the comparison group there were 17 (62.9%), 6 (22.3%) and 4 (14.8%) patients, respectively. All patients received a differentiated diet with the calculation of the energy value, the quota of protein (1.4—1.6 g), fat (1.2—1.4 g), carbohydrates (2—3 g) per 1 kg of ideal body weight and dosed physical activity. For assessing the indicators of the functional state of the disease we determined: the level of general bilirubin and its fractions (direct and indirect), activity of serum aminotransferases, alkaline phosphatase, total cholesterol content in the blood serum, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol, very‑low‑density lipoprotein cholesterol, triglycerides. Results. In the majority of patients with SLDMD, a statistically significant (p &lt;0.05) increase in the level of direct bilirubin in the blood, the activity of hepatic transaminases, alkaline phosphatase, and changes in the lipid spectrum of the blood were detected. According to the body mass index (BMI) most of the examined patients had visceral obesity. After the course of the combined therapy positive dynamics was marked in biochemical indices of the blood (p &lt;0.05): decrease of the direct bilirubin level, hepatic transaminases, blood phosphatase. The lipid spectrum of the blood was close to normal (p &lt;0.05). The addition of ursodeoxycholic acid to statin therapy contributes to a statistically significant reduction in total cardiovascular risk according to the SCORE 2 scale compared with atorvastatin monotherapy. All patients were recommended to continue the course of treatment (combination of atorvastatin and ursodeoxycholic acid) for 2 to 3 months. Conclusions. The use of a combination of statin and ursodeoxycholic acid in the treatment of patients with SLDMD and obesity helps to normalise the functional state of the liver and blood lipid parameters, reduce the degree of overall cardiovascular risk, and achieve clinical and biochemical remission of the pathological process in the liver.

Prevalence, characteristics, management, and outcomes of difficult-to-treat inflammatory bowel disease.

Criteria for "difficult-to-treat" Inflammatory Bowel Disease (IBD) (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD. We conducted a retrospective study in two tertiary centers in Italy. Among 1736 IBD patients treated with biologics/advanced small molecules, 430 (24.8%) met at least one DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action.In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (OR 6.55, 1.93-40.98, p=0.011; and OR 10.12, 3.01-63.14, p=0.002, respectively). In Crohn's disease (CD), multiple localizations (L3+L4) (OR 3.04, 1.09-8.34, p=0.03), stricturing (OR 2.24, 1.52-3.34, p<0.001) and penetrating (OR 2.33, 1.55-3.53, p<0.001) behaviors, and perianal disease (OR 2.49, 1.75-3.53, p<0.001) were the main risk factors for DTT.Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74, 1.27-2.41 p=0.001) but protective in UC (OR 0.65, 0.45-0.93 p=0.019).The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%).Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence. DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.

Survival in medullary thyroid carcinoma patients who fail to achieve a biochemical cure: implications of postoperative 1-month calcitonin levels and targeted therapy

PurposeThe survival rate of patients with medullary thyroid carcinoma (MTC) who fail to achieve a biochemical cure after surgery is reduced. This study aimed to investigate the prognostic factors affecting the survival of MTC patients who do not achieve a biochemical cure after surgery.MethodsCox univariate and multivariate proportional hazard models were used to determine the influence of different variables on overall survival (OS). Pearson’s chi-square test was used for categorical variables, and paired t-test was used for continuous variables.ResultsIn our study of 277 MTC patients treated between 2012 and 2022, there were 96 with raised postoperative 1-month calcitonin (Ct) levels (0–9.52 pg/ml). The overall survival (OS) rates of patients with high postoperative 1-month Ct values at 1, 3, and 5 years were 97.9%, 94.6%, and 86.8%, respectively. The univariate analysis revealed that patients with a postoperative 1-month Ct > 441.9 pg/ml had a greater risk of mortality than patients with postoperative 1-month Ct values ranging from 9.52 to 73.4 pg/ml (p = 0.043). Subsequent analyses revealed that receiving targeted therapy did not improve the OS of patients with distant metastasis among those with high postoperative 1-month Ct values (p = 0.527).ConclusionThis study confirmed that MTC patients who did not achieve biochemical remission after surgery had an increased risk of death when the Ct level was > 441.9 pg/ml 1 month after surgery. Additionally, for MTC patients who have not achieved biochemical remission and have experienced disease progression or distant metastasis after surgery, the use of targeted therapy does not prolong survival.

Low muscle mass is associated with efficacy of biologics in Crohn's disease

BackgroundLow muscle mass (LMM) can be a frequent complication in Crohn’s disease (CD). We attempted to explore the effect of LMM on the efficacy of biologics in patients with CD. MethodsThe retrospective cohort study included moderate-to-severe CD patients treated with infliximab or ustekinumab, and appendicitis patients as control. The skeletal muscle area (SMA) of L3 was assessed to evaluate the patients’ muscle mass. After propensity score matching, the impact of LMM on drug efficacy was assessed in CD patients. ResultsA total of 269 patients with CD and 172 appendicitis patients were included. The CD group had lower skeletal muscle density and BMI, and a higher risk of developing LMM than the control group. BMI (OR = 0.48, p < 0.001) and previous use of biologics (OR = 2.94, p = 0.019) were found to be independently associated with LMM. LMM was found to be associated with a decrease in clinical response (at weeks 8-14), clinical remission (at weeks 8-14, 24-30 and 52) and biochemical remission (at week 52). At weeks 24-30 and 52, LMM was independently associated with loss of response (LOR). We found LMM could be a predictor of lower clinical remission at week 30, lower clinical remission at week 52 and higher LOR rate at week 30 in infliximab. While in ustekinumab, LMM was associated with lower endoscopic remission at week 24, biochemical remission at week 52 and a higher LOR rate at weeks 24 and 52. ConclusionsThe prevalence of LMM was higher in the CD group compared to the control group. For CD patients with LMM, the efficacy of infliximab and ustekinumab was relatively poor in both the short-term and long-term.

Characterizing outcomes in a large cohort of latinx patients with autoimmune hepatitis

Introduction and ObjectivesThis study aimed to characterize a large cohort of Latinx patients with autoimmune hepatitis (AIH) and analyze clinical outcomes, including biochemical remission, duration of steroid treatment, fibrosis regression, and incidence of clinical endpoints (hepatic decompensation, need for liver transplant, and death). Materials and MethodsThis was a retrospective descriptive study of patients with biopsy proven AIH (2009–2019) at a single urban center. Demographics, medical comorbidities, histology, treatment course, biochemical markers, fibrosis using dynamic non-invasive testing (NIT), and clinical outcomes at three months and at one, two, and three years were analyzed. Results121 adult patients with biopsy-proven AIH were included: 43 Latinx (35.5%) and 78 non-Latinx (65.5%). Latinx patients were more likely to have metabolic dysfunction-associated steatotic liver disease (MASLD) (p = 0.004), and had higher Fibrosis-4 (FIB-4) (p = 0.0279) and AST-to-Platelet-Ratio-Index (APRI) (p = 0.005) at one year. Latinx patients took longer to reach biochemical remission than non-Hispanic Whites (p = 0.031) and longer to stop steroids than non-Hispanic Blacks (p = 0.016). There were no significant differences based on ethnicity in histological fibrosis stage at presentation or incidence of clinical endpoints. ConclusionsMASLD overlap is highly prevalent in Latinx AIH patients. Longer time to biochemical remission and worse NITs support that this population may have slower fibrosis regression with standard of care AIH treatment. This may indicate differing response rates due to genetic polymorphisms affecting drug metabolism and immune response among Latinx individuals and is less likely related to AIH/MASLD overlap based on the findings of this study.

Clinical and therapeutic implications of cavernous sinus invasion in pituitary adenomas.

Invasion of the cavernous sinus by pituitary adenomas impedes complete surgical resection, compromises biochemical remission, and increases the risk of further tumor recurrence. Accurate preoperative MRI-based diagnosis or intraoperative direct inspection of cavernous sinus invasion are essential for optimal surgical planning and for tailoring postoperative therapeutic strategies, depending on whether a total resection has been achieved, or tumoral tissue has been left in surgically inaccessible locations. The molecular mechanisms underlying the invasive behavior of pituitary adenomas remain poorly understood, hindering the development of targeted therapies. Some studies have identified genes overexpressed in pituitary adenomas invading the cavernous sinus, offering insights into the acquisition of invasive behavior. Their main limitation however lies in comparing purely intrasellar specimens obtained from invasive and non-invasive adenomas. Further, precise anatomical knowledge of the medial wall of the cavernous sinus is crucial for grasping the mechanisms of invasion. Recently, alongside the standard intrasellar surgery, extended endoscopic intracavernous surgical procedures with systematic selective resection of the medial wall of the cavernous sinus have shown promising results for invasive secreting pituitary adenomas. The first- and second-generation somatostatin agonist ligands and cabergoline are used with variable efficacy to control secretory activity and/or growth of intracavernous remnants. Tumor regrowth usually requires surgical reintervention, sometimes combined with radiotherapy or radiosurgery which is applied despite their benign nature. Unraveling the molecular pathways driving invasive behavior of pituitary adenomas and their tropism to the cavernous sinuses is the key for developing efficient innovative treatment modalities that could reduce the need for repeated surgery or radiotherapy.

P052 OPTIMAL ADRENAL VEIN SAMPLING LATERALIZATION CRITERIA FOR DIAGNOSIS OF UNILATERAL PRIMARY ALDOSTERONISM USING ALDOSTERONE CONCENTRATION MEASURED BY LC-MS/MS POST-ACTH STIMULATION

Background: Primary aldosteronism (PA) is characterized by excessive, autonomous secretion of aldosterone from one or both adrenal glands. Identification of unilateral disease and surgical resection can lead to cure, and is dependent on accurate criteria for lateralization of excess aldosterone during adrenal vein (AV) sampling (AVS). Current evidence for AVS lateralization cut-offs using plasma aldosterone concentration (PAC) measured by LC-MS/MS and post-surgical outcomes is limited. Aim: To determine optimal cut-off criteria to define lateralization of PA on AVS based on PAC measured by LC-MS/MS post-ACTH stimulation and post-surgical outcomes data. Methods: This study involved 60 subjects with PA who had PAC measured by LC-MS/MS post ACTH-stimulation during bilaterally-cannulated AVS, underwent unilateral adrenalectomy between July 2015-July 2021 and were followed up for ≥6 months. AVS lateralization parameters (lateralization index [LI; dominant PAC/cortisol(AV) ÷ non-dominant PAC/cortisol(AV)], contralateral suppression index [CSI; non-dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)], lateralization ratio [LR; dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)] and post-surgical outcome data were examined. Complete biochemical remission (CR) of PA post-surgery was defined using PASO International Consensus Criteria. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for LI, CSI and LR based on cases who achieved CR of PA post-surgery (n=55) vs those who did not (n=5). Results: Optimal cut-off LI during ACTH-stimulated AVS to identify unilateral PA cases who achieved CR post-surgery was 5.1 (AUC=0.92, P&lt;0.001; 92.7% sensitivity, 80.0% specificity) while the optimal cut-off for CSI was 0.6 (AUC=0.887, P&lt;0.001; 82.1% sensitivity, 100.0% specificity), and for LR was 3.3 (AUC=0.695, P=0.202; 80.0% sensitivity, 80.0% specificity). Cases with LR of 2.0-3.3 also achieved CR post-surgery if it was associated with CSI &lt;0.6. Conclusion: LI of &gt;5.1 provides high sensitivity and CSI &lt;0.6 high specificity for identification of surgically curable unilateral PA during ACTH-stimulated AVS when PAC is analyzed by LC-MS/MS.

Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry.

Switching from the intravenous to the subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from intravenous IFX (IV-IFX) to SC-IFX, the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch. Multicenter observational study involving CD and UC patients who were in clinical remission for at least 24 weeks and scheduled to switch from IV-IFX to SC-IFX. Two hundred and twenty patients were included [74 UC (34%) and 146 (66%) CD]. IV-IFX was administered for 52.5 months [range 25-89]. Pre-switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical parameters, C-reactive protein and faecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those with the intensified dose. Immunomodulator therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cut-off concentration for clinical and biochemical remission based on ROC analysis was 12.2 μg/mL (AUC: 0.62) at week 12 and 13.2 μg/mL (AUC: 0.57) at week 52. Drug persistence was 92% at week 52, with a good safety profile. Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cut-off point associated with remission was 12-13 μg/mL.

Short term effectiveness of ustekinumab versus vedolizumab in Crohn's disease after failure of anti-TNF agents: An observational comparative study design with a Bayesian analysis.

Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.