Long-term Remission Rates Research Articles

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.

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.

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

Initial treatment choices for long-term remission of chronic insomnia disorder in adults: a systematic review and network meta-analysis.

We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT-I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder. We searched multiple databases to December 27, 2023. We included trials in hypnotic-free adults with chronic insomnia comparing at least two of CBT-I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long-term remission. Secondary outcomes included all-cause dropout and self-reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random-effects network meta-analyses (CRD42024505519). We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT-I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15-2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88-3.30: moderate]) and no clear difference of CBT-I against combination (1.07 [95% CI, 0.63-1.80: moderate]). CBT-I was associated with fewer dropouts than pharmacotherapy. Short-term outcomes favored CBT-I over pharmacotherapy except total sleep time. Given the average long-term remission rate in the pharmacotherapy-initiating arms of 28%, CBT-I resulted in a long-term remission rate of 41% (95% CI, 31%-53%) and combination 40% (95% CI, 25%-56%). The current study found that starting with CBT-I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT-I alone.

Efficacy of Deep Brain Stimulation for Treatment-Resistant Depression: Systematic Review and Meta-Analysis

BackgroundTreatment-resistant depression affects about 30% of individuals with major depressive disorder. Deep brain stimulation is an investigational intervention for treatment-resistant depression with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side-effect profiles. MethodsWe conducted a systematic PubMed review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomized controlled trials (n = 198) and 8 open-label trials (n = 77) were included spanning 2009 to 2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery–Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at the last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates. ResultsDeep brain stimulation achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement of around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects than randomized controlled trials. Long-term (12–60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available. ConclusionsDeep brain stimulation produces significant chronic improvement in symptoms of treatment-resistant depression. However, the limited sham-controlled data do not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.

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.

Neurological Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors.

The use of immune checkpoint inhibitors (ICIs) for the treatment of various advanced and aggressive types of malignancy has significantly increased both survival and long-term remission rates. ICIs block crucial inhibitory pathways of the immune system, in order to trigger an aggravated immune response against the tumor. However, this enhanced immune activation leads to the development of numerous immune-related adverse events (irAEs), which may affect any system. Although severe neurological irAEs are relatively rare, they carry a high disability burden, and they can be potentially life-threatening. Therefore, clinicians must be alert and act promptly when individuals receiving ICIs present with new-onset neurological symptoms. In this narrative review, we have collected all the currently available data regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of post-ICI neurological irAEs. This review aims to raise physicians' awareness, enrich their knowledge regarding disease pathogenesis, and guide them through the diagnosis and management of post-ICI neurological irAEs.

Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience.

Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Efficacy and safety of laparoscopic Heller's myotomy versus pneumatic dilatation for achalasia: A systematic review and meta-analysis of randomized controlled trials.

We searched Cochrane CENTRAL, PubMed, Web of Science, SCOPUS and Embase for related clinical trials about patients suffering from achalasia. The quality appraisal and assessment of risk of bias were conducted with GRADE and Cochrane's risk of bias tool, respectively. Homogeneous and heterogeneous data was analyzed under fixed and random-effects models, respectively. The pooled analysis of 10 studies showed that PD was associated with a higher rate of remission at threemonths, oneyear, threeyears and fiveyears (RR = 1.25 [1.09, 1.42] (p = 0.001); RR = 1.13 [1.05, 1.20] (p = 0.0004); RR = 1.48 [1.19, 1.82] (p = 0.0003); RR = 1.49 [1.18, 1.89] (p = 0.001)), respectively. LHM was associated with lower number of cases suffering from adverse events, dysphagia and relapses (RR = 0.50 [0.25, 0.98] (p = 0.04); RR = 0.33 [0.16, 0.71] (p = 0.004); RR = 0.38 [0.15, 0.97] (p = 0.04)), respectively. There is no significant difference between both groups regarding the lower esophageal pressure, perforations, remission rate at twoyears, Eckardt score after oneyear and reflux. PD had higher remission rates than LHM at threemonths, oneyear and threeyears, but not at twoyears or fiveyears. More research is needed to determine whether PD has a significant advantage over LHM in terms of long-term remission rates.

Abstract 6704: Development and characterization of a tri-specific selective CD8 T cell engager (CD8xCD3xCD19) for treatment of B cell lymphoma

Abstract The recent development of CD3 bi-specific antibodies (BsAbs) targeting CD20, BCMA, GPRC5D and CD19 to treat B cell malignancies have resulted in significant clinical benefit to patients. However, long-term remission rates and survival remain to be demonstrated. Current CD3 BsAbs preferentially bind to and activate CD4 T cells. However, CD8 cytotoxic T cells also play the key role in anti-tumor response and T cell exhaustion in cancer immunity. To potentially enhance anti-tumor efficacy by augmenting CD8 T-cell response, we developed a novel tri-specific T cell engager (TriTE) IM-8319, which simultaneously binds human CD3, CD8 and CD19 epitopes with KD at 14.2 nM, 3.3 nM and 0.3 nM, respectively. The binding affinity to human CD8 T cells and CD4 T cells was measured with EC50 at 0.02 nM and 1.2 nM, respectively. In human PBMC-killing assays, IM-8319 was found to preferentially activate CD8 T cells with EC50 of 6.0 pM, compared to an EC50 of 94 pM for activating CD4 T cells. Unique cytokine release responses were seen with IM-8319 treatment. Compared to bi-specific TCE controls without CD8 binding domain, IM-8319 in human PBMC assays increased INFγ and TNFα in CD8 T cells and blunted IL-2 release in CD4 T cells. We observed robust cytotoxic killing of CD19+ B cells with IM-8319. Compared the bi-specific TCE controls lacking CD8 binding domain, in vitro CD19+ B-cell depletion was increased 6-fold with IM-8319. In addition, we observed notable structure activity relationships, with &amp;gt;100-fold increases in TriTE cytotoxicity with a weak CD3 binding domain. T-cell fratricide has hindered the development of antibodies containing 2+ T-cell epitopes. We observed correctable, dose-dependent CD8 T cell depletion at high concentrations of CD8xCD3xCD19 TriTEs in vitro and xenograft mouse models. This unwanted biological effect was not a surprise when the TriTE binds to CD8 T cells in trans. However, by structure engineering IM-8319 to allow for cis binding of CD3 and CD8, we effectively eliminated CD8 T cell fratricide at therapeutic doses. In a Raji-inoculated murine xenograft that was reconstituted with human PBMC, IM-8319 significantly inhibited tumor growth without obvious CD8 T cell depletion. In summary, we report a novel TriTE (IM-8319) that selectively binds to and activates CD8 T cells. IM-8319 results in robust on-target cytotoxicty with specific activation of CD8 T cells, suggesting potential to reduce systemic toxicities such as cytokine release syndrome (CRS) while augmenting direct antitumor efficacy. Further preclinical evaluation of IM-8319 is warranted in patients with B-cell leukemias and lymphomas. Citation Format: Zheng Yang, Wuzhong Shen, Guiyun Tu, Shenjie Xue, Ying Tan, Bingbin Xie, Jason Xu, Hanyang Chen, Shui Liu, Xiaoqiang Yan. Development and characterization of a tri-specific selective CD8 T cell engager (CD8xCD3xCD19) for treatment of B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6704.

Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease.

Postoperative data on Cushing's disease (CD) are equivocal in the literature. These discrepancies may be attributed to different series with different criteria for remission and variable follow-up durations. Additional data from experienced centers may address these discrepancies. In this study, we present the results obtained from 96 endoscopic transsphenoidal surgeries (ETSSs) for CD conducted in a well-experienced center. Pre- and postoperative data of 96 ETSS in 87 patients with CD were included. All cases were handled by the same neurosurgical team between 2014 and 2022. We obtained data on remission status 3-6 months postoperatively (medium-term) and during the latest follow-up (long-term). Additionally, magnetic resonance imaging (MRI) and pathology results were obtained for each case. The mean follow-up duration was 39.5±3.2 months. Medium and long-term remission rates were 77% and 82%, respectively. When only first-time operations were considered, the medium- and long-term remission rates were 78% and 82%, respectively. The recurrence rate in this series was 2.5%. Patients who showed remission between 3-6 months had higher longterm remission rates than did those without initial remission. Tumors >2 cm and extended tumor invasion of the cavernous sinus (Knosp 4) were associated with lower postoperative remission rates. Adenoma size and the presence/absence of cavernous sinus invasion on preopera-tive MRI may predict long-term postoperative remission. A tumor size of 2 cm may be a supporting criterion for predicting remission in Knosp 4 tumors. Further studies with larger patient populations are necessary to support this finding.

Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience.

Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of Pit- NET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

P520 Preferences towards treatment attributes among patients with Crohn’s disease and ulcerative colitis in Argentina, Australia, Brazil, Saudi Arabia and Taiwan: a discrete choice experiment

Abstract Background Advanced therapies (ATs) with different mechanisms of action and routes of administration (RoA) are used for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), and patients (pts) play an increasing role in the decision-making process.Pts’ preferences for treatment attributes from 7 European countries have been reported previously; however, evidence from non-European countries is lacking. Methods Adult pts with CD or UC on treatment for ≥6 months from Argentina, Australia, Brazil, Saudi Arabia and Taiwan were enrolled in this cross-sectional, self-administered online survey (Oct 2022 to May 2023). Pts’ preferences for IBD treatment attributes are described. In a discrete choice experiment, the relative importance of treatment attributes was estimated using conditional logit models. Results Overall, 706 pts with CD and UC (n=353 each) completed the survey. Mean (standard deviation [SD]) ages (years [y]) were 36.8 (9.9) and 37.7 (10.2), 47.9% and 47.6% were female, and mean (SD) disease durations (y) were 4.5 (6.0) and 4.6 (6.7) for CD and UC, respectively; 58.1% (CD) and 56.1% (UC) were exposed to ATs. For pts with CD, the rate of long-term remission on maintenance therapy (MT) was the most important attribute for treatment choice (32.5%), followed by the rate of 1-y remission (25.7%), RoA (24.6%) and risk of serious adverse events (AEs, 11.5%) and mild AEs (5.8%). For pts with UC, the rate of corticosteroid-free remission after 1 y was the most important attribute (30.8%), followed by RoA (27.4%), rate of mucosal healing after 1 y (16.1%), long-term remission on MT (14.9%) and risk of serious AEs (10.0%) and mild AEs (0.8%). Country-specific results are shown in the Table. Compared with intravenous administration every 4–8 weeks, pts with CD preferred subcutaneous (SC) administration every 1–2 weeks (odds ratio [95% confidence interval]: 1.41 [1.27–1.56] P&amp;lt;0.001) or every 4–12 weeks (1.22 [1.08–1.39, P=0.002]), and pts with UC preferred taking a tablet (1.41 [1.25–1.59], P&amp;lt;0.001) or SC administration every 4–12 weeks (1.30 [1.14–1.48], P&amp;lt;0.001) or every 1–2 weeks (1.20 [1.07–1.35], P=0.002). Pts exposed to ATs ranked the importance of RoA lower than that of effectiveness compared with AT-naïve pts, and 49.3% of pts with CD and 50.5% with UC indicated that they wanted ATs to start earlier. Conclusion This study highlights the importance of treatment effectiveness, RoA and safety for pts with IBD. Personalised care is crucial given that preferences for treatment attributes may vary across countries and among pts. Patient–physician shared decision-making discussions regarding therapy choice and timing should happen throughout the treatment journey.

Long-term remission rates and trajectory predictors in obsessive-compulsive disorder: Findings from a six-year naturalistic longitudinal cohort study

BackgroundThis naturalistic study, utilizing data from the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) cohort, investigated the long-term remission rates and predictors of different trajectories of obsessive-compulsive disorder (OCD) within a clinical population. MethodsA sample of 213 participants was classified into three illness trajectories: “Chronic,” “Episodic, ”and “Remitted-OCD.” Long-term remission rates were calculated based on three follow-up measurements over a 6-year period. A multinomial logistic regression model, incorporating five selected predictors with high explanatory power and one covariate, was employed to analyze OCD trajectory outcomes. ResultsThe long-term full remission rates, calculated from all the measurements combined (14%), were significantly lower than what was observed in earlier studies and when compared to assessments at each individual follow-up (∼30%). Moreover, high baseline symptom severity and early age of onset were identified as significant risk factors for a chronic course of OCD, while male sex and younger age predicted a more favorable trajectory. Notably, the likelihood of an episodic course remained high even without identified risk factors. LimitationsThe bi-annual data collection process is unable to capture participants' clinical conditions between assessments. Additionally, no data was collected regarding the specific type and duration of psychological treatment received. Regarding the type of treatment participants received. ConclusionsResults suggest that long-term remission rates may be lower than previously reported. Consequently, employing multiple assessment points in longitudinal studies is necessary for valid estimation of long-term full remission rates. The results emphasize the importance of personalized clinical care and ongoing monitoring and maintenance for most OCD cases.

Clinical Characteristics and Outcomes of Prolactinomas in Children and Adolescents: A Large Retrospective Cohort Study.

Prolactinoma, the most common subtype of pituitary adenoma, is rare in children and adolescents. Clinical presentation and treatment outcomes of prolactinomas in this population have been evaluated insufficiently. To summarize the clinical features, both medication and surgical outcomes of prolactinomas in children and adolescents in a large retrospective cohort from China. A cohort of patients with prolactinomas aged ≤20 years at diagnosis between 2012 and 2021 in Peking Union Medical College Hospital were retrospectively analyzed. The cohort comprised 170 patients (115 females and 55 males, median age 16.6 years), with 20.0% (23/115) girls without menarche and 33.3% (18/54) boys in prepuberty. The median maximal diameter was 15.0 mm (61.2% macroadenomas and 4.6% giant adenomas), and the median baseline prolactin (PRL) level was 211.0 ng/mL. Larger sizes and higher PRL levels were observed in girls without menarche at diagnosis and in boys. Most girls presented with menstrual disturbance (86.7%), and boys were frequently bothered by headaches (42.6%), reduced height velocities (25.9%), and delayed puberty (18.2%). Dopamine agonists (DAs) were used as first-line treatment in 133 patients, and the resistance rate was 22.5% (25/111), independently associated with maximal tumor diameters (P = .035). Surgery was performed in 76 patients. Long-term surgical remission rates were 32.9% (25/76) overall, negatively associated with cavernous sinus invasion independently (P = .025), 59.4% (19/32) in noninvasive tumors (64.0% in 25 noninvasive macroadenomas), and 5.0% (1/20) in invasive tumors. Pediatric prolactinomas exhibited more severe clinical characteristics in boys and in patients diagnosed during earlier stages of pubertal developments. Given the overall efficacy of PRL normalization by medication and considerable surgical remission rate in noninvasive tumors, DAs remain the first-line recommendation for prolactinomas in children and adolescents, while surgery might be viable for noninvasive tumors.

Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series

Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. To report on outcomes of ETSS in a cohort of prolactinomas. Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. Median preoperative prolactin levels were 166 (98-837 µg/L; males 996 [159-2145 µg/L] vs. females 129 [84-223 µg/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p=0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p=0.002). Transient DI (n=29, 21.2%) was the most frequent complication. Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

FRI299 Efficacy And Safety Of Endoscopic Transsphenoidal Resection For Prolactinoma: A Retrospective Case-series

Abstract Disclosure: I.M. Zandbergen: None. K. Huntoon: None. T.G. White: None. F. de Vries: None. B. Moclair: None. W.R. Van Furth: None. I.C. Pelsma: None. A. Dehdashti: None. N.R. Biermasz: None. D.M. Prevedello: None. Introduction Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is mainly reserved for patients with dopamine agonist (DA) resistance, intolerance, or apoplexy. Surgery as a first-line treatment remains a topic of debate. Therefore, published patient cohorts are often not representative for the total population, and lack long-term follow-up. High remission rates (overall 67%, microprolactinoma up to 90%) have been reported, with recurrence in 5-20%, and low complication rates. This study aimed to assess clinical efficacy and safety of ETSS in prolactinoma patients. Study design Multicenter retrospective chart review of 137 surgically treated prolactinoma patients (mean age 38.2±13.7 years; 61.3% female) from three tertiary care centers from the USA and the Netherlands. Clinical characteristics and outcomes of surgery, including long-term (&amp;gt;2 years postoperatively) biochemical remission, resolution of hypogonadism and visual deficiencies, and recurrence and complication rates were assessed. Main results Median highest preoperative prolactin levels -available for 115 patients- were 168.5 µg/L (97.5 - 836.5 µg/L) and were higher for males (996.4 µg/L (158.6 - 2145.0 µg/L) vs females 128.5 µg/L (83.7 - 223.0 µg/L), P&amp;lt;0.001). The cohort consisted of 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas, whereas in 5 (3.6%) patients no adenoma was detectable by MRI. Males had more macroprolactinomas: 38 (71.7%) vs 31 females (36.9%), P&amp;lt;0.001; and giant prolactinomas: 7 (13.2%) vs 0 females (0.0%), P&amp;lt;0.001. Pituitary deficiencies -available for 135 patients- were present in 51 (37.8%) patients, with 8 (5.9%) having panhypopituitarism, and 43 (31.9%) had deficiencies of LH and 41 (30.4%) in FSH. Males more often showed any pituitary deficiency: 32 (61.5%) vs 19 females (22.9%), P&amp;lt;0.001, with correspondingly higher rates of deficiencies of all pituitary axes. Most often reported indication for surgery was DA intolerance 59 (43.1%) patients; males 14 (26.4%) vs females 45 (53.6%), P=0.006, with complete resection being the intent of surgery in 109 (79.6%) patients (males 33, 62.3%; vs females 76, 90.5%, P&amp;lt;0.001). With a median follow-up of 28.0 (15.0 - 55.5) months, long-term DA free remission was achieved in 87 (63.5%) patients. Males had lower remission rates: 25 (47.2%) vs 62 females (73.8%), P=0.002, with similar median follow-up for males and females. Occurring in 29 (21.2%) patients, transient DI was the most frequently reported surgical complication, similar for males and females. Conclusions In this multinational retrospective case-series of 137 prolactinoma patients who underwent ETSS, with relatively high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5%. Both preoperative clinical characteristics and remission rates were significantly different between males and females. Presentation: Friday, June 16, 2023

Corticotropin-releasing hormone test predicts the outcome of unilateral adrenalectomy in primary bilateral macronodular adrenal hyperplasia

PurposePrimary bilateral adrenal hyperplasia (PBMAH) is associated with hypercortisolism and a heterogeneous clinical expression in terms of cortisol secretion and related comorbidities. Historically, treatment of choice was bilateral adrenalectomy (B-Adx); however, recent data suggest that unilateral adrenalectomy (U-Adx) may be an effective alternative. For the latter, factors predicting the postsurgical outcome (e.g., biochemical control) have not been identified yet.MethodsPBMAH patients undergoing U-Adx for overt Cushing’s syndrome (CS) in two tertiary care centers were retrospectively analysed. Remission was defined as a normalization of urinary free cortisol (UFC) without the need for medical treatment. The potential of hCRH test as a predictor of U-Adx outcome was evaluated in a subgroup.Results23 patients were evaluated (69% females, mean age 55 years). Remission rate after U-Adx was 74% at last follow up (median 115 months from UAdx). Before U-Adx, a positive ACTH response to hCRH (Δ%ACTH increase > 50% from baseline) was associated with higher remission rates.ConclusionsThree of four patients with PBMAH are surgically cured with U-Adx. Pre-operative hCRH testing can be useful to predict long-term remission rates.

Detailed immunophenotyping of the hematopoietic graft from patients with multiple sclerosis undergoing autologous hematopoietic stem cell transplant

Background aimsAutologous hematopoietic stem cell transplantation (AHSCT) is a highly effective therapy for relapsing multiple sclerosis. Re-infused stem cells provide “rescue” from the pancytopenia induced by immuno-chemotherapy. To date, no study has analyzed the non-stem cell content of the leukapheresis product (graft) in regards to its influence on disease remission in AHSCT for multiple sclerosis (MS). MethodsDetailed immunophenotyping of the stem cell graft was performed in a cohort of highly active patients with MS (n = 22) followed for a median of 6 years’ post-AHSCT. ResultsEffector memory populations thought to house pathogenic clones including Th17 cells and central nervous system homing T cells were detected in the graft at similar proportions to pre-AHSCT. There was no association between absolute counts of these populations in the graft and treatment response. Only in responder patients was there evidence of a significant decrease in these putative pro-inflammatory populations by 3 months’ post-transplant. Although there was no statistical difference in the number of T regulatory cells (Tregs) in the graft between responders and relapsing patients, the absolute count of Tregs in the graft correlated with circulating Tregs in the first 6 months post-AHSCT in responders alone. ConclusionsOur results collectively suggest that the early establishment of immune tolerance post-AHSCT appears to relate to a decrease in putative pathogenic cell populations following reinfusion, and that Treg load in the leukapheresis product is less relevant to treatment response than the early expansion of graft-derived Tregs. It therefore remains unclear whether employment of CD34 selection to manipulate the graft may offer additional benefit in remission rates post-AHSCT for MS. Cellular therapy targeted toward early Treg expansion may provide recourse for long-term remission rates in MS.

A clinicopathological and prognostic study of 18 children with C1q nephropathy and focal segmental glomerulosclerosis: an 18-year experience from a single center.

C1q nephropathy is a relatively rare glomerulonephritis characterized by dominant mesangial deposition of C1q. Even though C1q nephropathy has been described for more than three decades, the clinicopathological features and renal outcomes remain unclear. C1q nephropathy maypresent diverse morphological patterns, including focal segmental glomerulosclerosisand, the notion of C1q nephropathy as a separate disease entity is still debated. This study aimed to describe the clinical and prognostic relevance of C1q nephropathy in children with primary focal segmental glomerulosclerosis. Three hundred eighty-nine children were diagnosed with primary focal segmental glomerulosclerosis in Jinling Hospital from 2003 to 2020. Among them, 18 cases fulfilled the criteria for C1q nephropathy. We then selectedas a control group 18 children with primary focal segmental glomerulosclerosis without C1q nephropathy matched to those with C1q nephropathy for age, sex, and period of renal biopsy. Clinical and prognostic parameters were compared in children with and without C1q nephropathy. Renal end-point was defined as a ≥ 40% reduction in estimated glomerular filtration rate or end-stage renal disease. Four point sixty-three percent (18/389) of primary focal segmental glomerulosclerosis cases were diagnosed with C1q nephropathy. The male-to-female ratio of patients diagnosed with C1q nephropathy was 1:1. The median age at biopsy and age at onset was 15.63 (13.00-16.50) years and 14.50 (9.00-16.00) years, respectively. The prevalence of nephrotic syndrome, hematuria, and hypertension was 38.90% (7/18), 72.20% (13/18), and 33.30% (5/18), respectively. Four (22.2%) patients were steroid-dependent, 13 (72.2%) patients were steroid-resistant, and 1 (5.6%) patient developed secondary steroid-resistance. During a follow-up of 52.24 (25.00-72.47) months, 10 (55.6%) patients achieved remission, and 5 (27.8%) progressed to theend-point [including 2 (11.11%) patients who developed end-stage kidney disease]. There was no significant difference in the estimated end-stage renal disease-free survival rates, the estimated end-point-free survival rates, and the long-term remission rate between patients with and without C1q nephropathy (Kaplan-Meier, Log-rank, all P > 0.05). C1q nephropathy was rare in pediatric patients withfocal segmental glomerulosclerosis. These patients usually had poor response to steroids. The long-term renal outcomes and remission of children with primary focal segmental glomerulosclerosis with C1q nephropathy were comparable to those without C1q nephropathy.