First-line Treatment Of Choice Research Articles

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Abstract PO4-05-08: Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China

Abstract Background: Endocrine therapy resistance was classifed as primary and secondary, guiding the first-line (1L) treatment choices for hormone receptor positive, HER2-negative (HR+/Her2-) metastatic breast cancer (mBC). However, it is unknown whether it is primary ET resistance or not to the stage IV de novo patients. Therefore, We performed a retrospective study to predict primary resistance in advance in de novo patients and have a more appropriate treatment strategy. Methods: We identified newly diagnosed with stage IV de novo HR+/HER2- mBC patients received single-agent endocrine therapy (ET) or ET plus CDK4/6 inhibitors (CDK4/6i) in 1L setting from January 1, 2020 to Jun 30, 2022, using the National Cancer Information Database (NCID) in China. Primary ET resistance (PER) was defined as switching to second-line treatment within 6 months after receiving the 1L ET±CDK4/6i, whereas secondary ET resistance (SER) patients were those who received 1L ET±CDK4/6i treatment more than six months. The Chi-Square test was used to compare the baseline characteristics of PER and SER patients. Result: A total of 217 patients who met the inclusion criteria were included in the analysis, among which 161 patients received single-agent ET and 56 patients received ET plus CDK4/6i. 18.4% of the patients were classified as PER patients, whereas 81.6% showed SER patients. PER patients were younger (median age of 52 years vs. 58 years in SER patients, p=0.01). In terms of clinicopathological characteristics, patients with PER have a higher percentage of liver metastases (14/40 (35%) vs. 20/177 (11.3%) in SER, p&amp;lt; 0.01), distant lymph node metastases (19/40 (34%) vs. 45/177 (25.4%) in SER, p = 0.01), and bone metastases (30/40(75%) vs. 97/177(54.8%) in SER, p = 0.02). Furthermore, the PER rate was 21.7% (35/161) in patients received single-agent ET, compare with 8.9% (5/56) in ET plus CDK4/6i patients, p=0.04. Regarding the following treatment pattern in the PER patients, a high percentage of patients received chemotherapy, accounting for 50%, 30% still received another endocrine therapy, and the remaining 20% patients received CDK4/6i combined with endocrine therapy. Conclusions: There is still a significant proportion of de novo HR+/HER2- mBC patients with primary endocrine resistance, a relatively low proportion of PER in patients receiving endocrine in combination with CDK4/6i. Table. The proportion of primary endocrine resistance across treatment regimens in de novo HR+/HER2- metastatic breast Cancer Citation Format: Zhanhong Chen, Xiying Shao, Yabing Zheng, Wenming Cao, Junqing Chen, Weizhu Wu, Ting Wang, Xiaojia Wang. Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-08.

Principles in the Management of Glioblastoma.

Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in understanding the pathophysiology of these tumours have not translated into significant achievements in therapies or survival outcomes for patients. Progress in molecular profiling has yielded new omics data for a more refined classification of glioblastoma. Several typical genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signalling, as well as mutation of isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), amplification of epidermal growth factor receptor vIII, and codeletion of 1p/19q. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. Effective treatment options for glioblastoma are limited. Surgery, radiotherapy, and alkylating agent chemotherapy remain the primary pillars of treatment. Only promoter methylation of the gene MGMT predicts the benefit from alkylating chemotherapy with temozolomide and it guides the choice of first-line treatment in elderly patients. Several targeted strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles are under investigation in clinical trials. This review explores the potential genetic and epigenetic biomarkers that could be deployed as analytical tools in the diagnosis and prognostication of glioblastoma. Recent clinical advancements in treating glioblastoma are also discussed, along with the potential of liquid biopsies to advance personalized medicine in the field of glioblastoma, highlighting the challenges and promises for the future.

Speech Outcomes After Palatal Lengthening Via Double Opposing Buccinator Myomucosal Flaps.

Palatal lengthening is becoming a first-line treatment choice for cleft patients with velopharyngeal insufficiency (VPI). As cleft palate-related surgical outcomes are age dependent, speech outcomes may be similarly affected by patient age at the time of treatment. The primary goal of this study is to determine whether there are age-related speech outcome differences when double opposing buccinator myomucosal flaps are used as part of a palatal lengthening protocol and whether these outcome differences preclude utilization of this technique for specific patient age groups. A retrospective study was performed on consecutive nonsyndromic patients with VPI who underwent treatment using double opposing buccinator myomucosal flaps at our hospital between 2014 and 2021. Patients who completed the 15-month follow-up were stratified by age. Group A aged between 2 and 7 years (n = 14), group B aged 8 and 18 years (n = 23), and group C aged older than 18 years (n = 25) were included. Standardized perceptual speech evaluations and nasopharyngoscopy were performed. Hypernasality, soft palate mobility, and lateral palatal wall mobility were assessed both preoperatively and at a 15-month postoperative interval. Complications were also recorded. The χ2 test was used for statistical comparison. All of the age-stratified patient groups in this study showed significant improvement in hypernasality, soft palate mobility, and lateral wall mobility (P < 0.01), with no statistically significant differences between the different patient age groups. Overall speech success was achieved in 69.4% of patients. Patients in group A achieved 78.6% speech success, patients in group B achieved 78.3% speech success, and patients in group C achieved 56% speech success, with no statistically significant differences being shown regarding speech success between the different patient age groups (P > 0.05). Regardless of age, palatal lengthening via double opposing buccinator myomucosal flaps similarly improves speech outcomes.

Abstract 2542: Real-world validation of the PurIST classifier demonstrates enhanced therapy selection for pancreatic ductal adenocarcinoma (PDAC) patients

Abstract Background: PDAC is a particularly fatal condition lacking established biomarkers for the choice of first-line treatment (1L). The PurIST algorithm is a gene signature (Rashid et al. Clin. Cancer Res., 2020) that categorizes PDAC tumors into basal or classical molecular subtypes and has been previously validated in a patient cohort of advanced PDAC (N=258). In this post-hoc analysis study, we examine whether the PurIST subtypes can distinguish patients likely to respond to FOLFIRINOX (FFX) versus Gemcitabine + nab-paclitaxel (GnP). Methods: A cohort of de-identified PDAC patients was selected from the Tempus Oncology Database following an IRB-approved protocol. Inclusion criteria required no prior systemic treatment, a surgically unresectable/metastatic status, available RNA-sequencing data from primary or metastatic tissue, and the use of FFX or GnP as 1L systemic therapy with documented outcomes. RNA-sequencing was generated by the CAP/CLIA validated Tempus xR assay. The PurIST gene signature was applied to normalized gene expression values to classify samples into basal or classical subtypes. Univariate and multivariate Cox PH analyzes comparing overall survival (OS) with adjustment for delayed entry, between two common 1L treatment regimens, FFX and GnP, were performed for classical patients with an ECOG performance status of 0 or 1. Results: Application of the PurIST model to the PDAC cohort (N=258) resulted in 67% (N=173) labeled as classical, 23% (N=59) as basal, and the remainder as no-call. Amongst classical patients, 35% (N=61) had a known ECOG score of 0 or 1 and were retained for subsequent analysis. Within this subset, 37 were treated with FFX and 24 with GnP as 1L, with an overall median OS of 11.4 months (95% CI: 9.5-16.5) and a 12-month survival rate of 47.2%. A univariate Cox PH analysis showed that classical patients treated with FFX had a significantly longer OS time (HR (95% CI) = 2.32 (1.29-4.17)). This result remained significant in a multivariate Cox PH, adjusting for age and ECOG, (HR=2.5 (1.15-5.44)). Conclusion: In this real-world cohort of advanced PDAC patients, we showed that classical patients with low ECOG scores had superior OS with 1L FFX treatment compared to 1L GnP. These findings demonstrate the potential for PurIST to aid in optimal treatment selection for patients with advanced PDAC. Citation Format: Stephane Wenric, James M. Davison, John Guittar, Gregory M. Mayhew, Kirk Beebe, Alia Zander, Seung Won Hyun, Kyle Beauchamp, Michael V. Milburn, Vincent Chung, Tanios S. Bekaii-Saab, Charles M. Perou. Real-world validation of the PurIST classifier demonstrates enhanced therapy selection for pancreatic ductal adenocarcinoma (PDAC) patients [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 2542.

Cost-effectiveness analysis of amivantamab plus chemotherapy versus chemotherapy alone in NSCLC with EGFR Exon 20 insertions.

Amivantamab plus chemotherapy has been proved to be an efficient treatment strategy for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions. The aim of this study was to conduct the cost-effectiveness analysis of amivantamab-chemotherapy compared with chemotherapy alone in NSCLC harboring EGFR exon 20 insertion mutations. We constructed a Markov model based on the data derived from the PAPILLON trial. We evaluated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to evaluate the influence of different parameters on this model. Compared with chemotherapy alone, amivantamab combined with chemotherapy treatment gained an incremental effectiveness of 0.473 QALYs and an incremental cost of $361,950.952, which resulted in an ICER of $765,224/QALY. The ICER was much higher than the willingness-to-pay threshold of 15,0000/QALY. One-way sensitivity analysis revealed that amivantamab cost was the leading influential factor in the model. Compared with chemotherapy alone, amivantamab plus chemotherapy is not a cost-effective first-line treatment choice for NSCLC patients with EGFR exon 20 insertions. The costly price of amivantamab is one of the major reasons for the high cost of this combined treatment strategy. Therefore, it is imperative to take into account the high cost of amivantamab in the subsequent clinical application and strive to attain a relative equilibrium between its significant clinical benefit and economic encumbrance.

Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas.

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective β-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.

An integrated precision medicine approach in major depressive disorder: a study protocol to create a new algorithm for the prediction of treatment response.

Major depressive disorder (MDD) is the most common psychiatric disease worldwide with a huge socio-economic impact. Pharmacotherapy represents the most common option among the first-line treatment choice; however, only about one third of patients respond to the first trial and about 30% are classified as treatment-resistant depression (TRD). TRD is associated with specific clinical features and genetic/gene expression signatures. To date, single sets of markers have shown limited power in response prediction. Here we describe the methodology of the PROMPT project that aims at the development of a precision medicine algorithm that would help early detection of non-responder patients, who might be more prone to later develop TRD. To address this, the project will be organized in 2 phases. Phase 1 will involve 300 patients with MDD already recruited, comprising 150 TRD and 150 responders, considered as extremes phenotypes of response. A deep clinical stratification will be performed for all patients; moreover, a genomic, transcriptomic and miRNomic profiling will be conducted. The data generated will be exploited to develop an innovative algorithm integrating clinical, omics and sex-related data, in order to predict treatment response and TRD development. In phase 2, a new naturalistic cohort of 300 MDD patients will be recruited to assess, under real-world conditions, the capability of the algorithm to correctly predict the treatment outcomes. Moreover, in this phase we will investigate shared decision making (SDM) in the context of pharmacogenetic testing and evaluate various needs and perspectives of different stakeholders toward the use of predictive tools for MDD treatment to foster active participation and patients' empowerment. This project represents a proof-of-concept study. The obtained results will provide information about the feasibility and usefulness of the proposed approach, with the perspective of designing future clinical trials in which algorithms could be tested as a predictive tool to drive decision making by clinicians, enabling a better prevention and management of MDD resistance.

Evaluating Policies of Expanding Versus Restricting First-Line Treatment Choices: A Cost-Effectiveness Analysis Framework

ObjectivesHealthcare payers often implement coverage policies that restrict the utilization of costly new first-line treatments. Cost-effectiveness analysis can be conducted to inform these decisions by comparing the new treatment with an existing one. However, this approach may overlook important factors such as treatment effect heterogeneity and endogenous treatment selection, policy implementation costs, and diverse patient preferences across multiple treatment options. We aimed to develop a cost-effectiveness analysis framework that considers these real-world factors, facilitating the evaluation of alternative policies related to expanding or restricting first-line treatment choices. MethodsWe introduced a metric of incremental cost-effectiveness ratio (ICER) that compares an expanded choice set (CS) including the new first-line treatment with a restricted CS excluding the new treatment. ICER(CS) accounts for treatment selection influenced by heterogeneous treatment effects and policy implementation costs. We examined a basic scenario with 2 standard first-line treatment choices and a more realistic scenario involving diverse preferences toward multiple choices. To illustrate the framework, we conducted a retrospective evaluation of including versus excluding abiraterone acetate plus prednisone (AAP) (androgen deprivation therapy [ADT] + AAP) as a first-line treatment for metastatic hormone-sensitive prostate cancer. ResultsThe traditional ICERs for ADT + AAP versus ADT alone and ADT+ docetaxel were $104 269 and $206 324/quality-adjusted life-year, respectively. The ICER(CS) for comparing an expanded CS with ADT + AAP with a restricted CS without ADT + AAP was $123 179/quality-adjusted life-year. ConclusionsThe proposed framework provides decision makers with policy-relevant tools, enabling them to assess the cost-effectiveness of alternative policies of expanding versus restricting patients’ and physicians’ first-line treatment choices.

Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma.

Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP3) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.

Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (PRRT2) are the most common genetic cause of PKD. The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations. We enrolled 219 PKD patients, documented their clinical information and performed PRRT2 screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without PRRT2 variants. Genotype-phenotype correlation analyses were conducted on the probands. Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 PRRT2 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without PRRT2 variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% versus 8.99%, respectively). Patients with truncated PRRT2 variants tend to have bilateral attacks. We identified two transmembrane protein 151A (TMEM151A) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD. These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated PRRT2 variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of PRRT2 and TMEM151A variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

Advanced breast cancer (ABC) that is positive for hormone receptors (HRs) and human epidermal growth factor receptor 2 (HER2) is a cancer subtype with distinctive characteristics. The primary treatment guidelines suggest that a combination therapy comprising anti-HER2 therapy and chemotherapy should be administered as the initial treatment for HR-positive/ HER2-positive (HR+/HER2+) ABC. However, crosstalk between the HR and HER2 pathways can partially account for the resistance of HR+/HER2+ disease to HER2-targeted therapy. This, in turn, provides a rationale for the concomitant administration of HER2-targeted therapy and endocrine therapy (ET). Many clinical studies have confirmed that the combination of HER2-targeted therapy and ET as a first-line treatment is not inferior to the combination of HER2-targeted therapy and chemotherapy, and support its use as a first-line treatment choice for HR+/HER2+ ABC. Other drugs, such as antibody-drug conjugates, cyclin-dependent kinase 4/6 inhibitors, phosphatidylinositol 3-kinase-protein kinase B (AKT)-mammalian target of rapamycin inhibitors, and programmed cell death protein 1 or programmed cell death ligand 1 inhibitors, may also improve the prognosis of patients with breast cancer by blocking signaling pathways associated with tumor proliferation and break new ground for the treatment of HR+/HER2+ ABC.

Atrial Fibrillation Ablation: Current Practice and Future Perspectives.

Catheter ablation to perform pulmonary vein isolation (PVI) is established as a mainstay in rhythm control of atrial fibrillation (AF). The aim of this review is to provide an overview of current practice and future perspectives in AF ablation. The main clinical benefit of AF ablation is the reduction of arrhythmia-related symptoms and improvement of quality of life. Catheter ablation of AF is recommended, in general, as a second-line therapy for patients with symptomatic paroxysmal or persistent AF, who have failed or are intolerant to pharmacological therapy. In selected patients with heart failure and reduced left-ventricular fraction, catheter ablation was proven to reduce all-cause mortality. Also, optimal management of comorbidities can reduce AF recurrence after AF ablation; therefore, multimodal risk assessment and therapy are mandatory. To date, the primary ablation tool in widespread use is still single-tip catheter radiofrequency (RF) based ablation. Additionally, balloon-based pulmonary vein isolation (PVI) has gained prominence, especially due to its user-friendly nature and established safety and efficacy profile. So far, the cryoballoon (CB) is the most studied single-shot device. CB-based PVI is characterized by high efficiency, convincing success rates, and a beneficial safety profile. Recently, CB-PVI as a first-line therapy for AF was shown to be superior to pharmacological treatment in terms of efficacy and was shown to reduce progression from paroxysmal to persistent AF. In this context, CB-based PVI gains more and more importance as a first-line treatment choice. Non-thermal energy sources, namely pulsed-field ablation (PFA), have garnered attention due to their cardioselectivity. Although initially applied via a basket-like ablation tool, recent developments allow for point-by-point ablation, particularly with the advent of a novel lattice tip catheter.

#334 : Tackling Complex Infertility Patient: A Case Report

Background: Infertility is a common problem presented in women with endometriosis especially as it is often associated with poor quality of life. Therefore, surgical Intervention has been considered as the first-line treatment of choice. On the other hand, surgery itself has detrimental effects on ovarian reserve and is associated with ovarian failure. Case Report: We present a case of a 39-year-old woman para 1 with multiple myoma uteri, bilateral endometriosis cyst, left hydrosalpinx, deep infiltrating endometriosis (DIE), and adhesion (Figure 1). She comes with a history of heavy abnormal uterine bleeding, lower abdominal pain, and unable to conceive 11 years after their first child despite adequate unprotected intercourse. The patient was anemic (Hemoglobin 7.30 g/dL) with low Anti Mullerian Hormone (AMH; 0.26 mg/ml). We decided to perform laparoscopic uterine myoma with multiple bilateral endometrial cysts, left salpingectomy, and adhesiolysis (Figure 2). Patient then underwent an ultra-long protocol with three cycles of leuprolide acetate 3.75 mg. Ovum pick-up was performed and we retrieved five M-II oocytes and from embryo culture, two embryos with good and moderate quality were collected for vitrification procedure. Prior frozen embryo transfer, extra acetylsalicylic acid 80 mg once a day and estradiol valerate 4 mg thrice a day were given for 18 days. The patient soon became pregnant after a few weeks of embryo transfer with βHCG of 185 mIU/m. Conclusion: Individualized treatment plans based on the patient’s symptoms and respective reproductive goals are important points to be discussed in endometriosis-associated infertility patients. Surgical intervention before IVF/ICSI is deemed as necessary to preserve ovarian reserve and to restore normal anatomy to increase the success rate of embryo implantation.

Temporal trends of first time antihypertensive treatment among citizens over 75 years - a register-based, cohort study

Abstract Background Hypertension is highly prevalent, particularly among the increasingly large elderly population. There is a need for investigating the use of antihypertensive drugs in elderly patients. Data on clinicians’ first drug of choice, effectiveness, and magnitude of use are sparse, partly due to older patients often being excluded from clinical trials which in turn limits knowledge about their cardiovascular drug safety. Furthermore, drug metabolism and pharmacokinetics are known to differ with increasing age. Purpose To investigate temporal trends for first-line drug choice for first time antihypertensive treatment among elderly patients over 75 years from 2000-2021. Methods Using nationwide registers, we identified all patients over 75 years initiated on either beta blockers (BB), calcium channel blockers (CCB), renin-angiotensin system inhibitors (RASi), thiazides, or a combination between 2000-2021. Patients treated earlier in life with any antihypertensive drug were excluded, as were patients with atrial fibrillation, heart failure, chronic kidney disease, and acute coronary syndrome. Patients were included on the date of their first claimed prescription and temporal trends were reported as proportions per calendar year. We described adherence, change or discontinuation of antihypertensive medication using additionally claimed prescriptions during the first 180 days following study entry. Only patients alive 180 days after initial inclusion contributed to the latter analysis. Results A total of 187,309 patients (median age 80 years [interquartile range (IQR) :77-84], 59.1% female) were eligible for inclusion. The first drug of choice for antihypertensive treatment in patients above 75 years of age has changed markedly between 2000 (BB 12.7%, CCB 22.3%, RASi 11.6%, thiazides 61.3%, and combinations 2.6%) and 2021 (BB 12.9% CCB 28.2%, RASi 48.2%, thiazides 8.0%, and combinations 2.7%), especially for RASi and thiazides (Figure 1). Following the first 180 days, 172,756 patients (median age 80 [IQR:77:84], 59.3% female) were still alive and eligible. Adherence, discontinuation, and shift varied according to first drug of choice. Discontinuation within 180 days was highest among patients initiated on thiazides 19,544 (28.4%) whereas most patients continued the same 1-drug regimen if they started on RASi (64.6%), BB (57.8%), and CCB (59.5%). The highest proportion who had a second drug added within 180 days were patients initiated on CCB (21.1%) and RASi (21.1%) (Figure 2). Conclusion Elderly patients initiated on antihypertensive medication for the first time after the age of 75 is a substantial patient group, and from 2000–2021 a preference for thiazides has largely been replaced by RASi and CCB. It seemed that patients initiated on thiazides were more likely to discontinue or shift shortly afterwards. Further evaluation of thiazides as an equal first drug of choice for hypertension in the elderly could be warranted.

Elderly-Onset Rheumatoid Arthritis: Characteristics and Treatment Options.

Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.

Preferences for the sequencing of first-line systemic treatments in metastatic hormone receptor-positive, HER2-negative breast cancer.

Metastatic breast cancer (MBC) is a diverse disease. Therapeutic options include hormonal therapy, chemotherapy, and targeted therapies. The optimal treatment sequence for patients with hormone receptor-positive (HR-positive), HER2-negative metastatic breast cancer remains unknown. This was a retrospective and prospective study. The data was collected from the medical records of patients in a tertiary healthcare center in Lebanon between the years 2016 and 2019, and patients were followed up for a 3-year duration. The main aim was to identify oncologists' preferences in the choice and sequence of treatment for newly diagnosed and/or recurrent cases of HR-positive, HER2-negative MBC. A total of 51 patients were included. 24 patients received chemotherapy, while 27 received endocrine therapy as first-line treatment after a diagnosis of MBC, with a median overall survival (OS) of 13 months and a median progression-free survival (PFS) of 12 months after first-line treatment with chemotherapy, compared to 27 months and 18 months with endocrine therapy. A higher percentage of patients have received chemotherapy in the first-line setting compared to the data reported in the literature, with the choice being multifactorial. Factors to consider in MBC management include the choice of first-line treatment, the optimal sequence of treatment, and the combination of available treatment options.

Glucocorticoid-induced osteoporosis: an overview with focus on its prevention and management.

The widespread use of glucocorticoids (GCs) contributes to the effective management of several diseases and conditions. However, it comes at a price in the case of the bones causing glucocorticoid-induced osteoporosis (GIOP), the most common cause of secondary osteoporosis and fractures. Several scientific societies have issued comprehensive guidelines on the optimal management of patients receiving GCs with the aim of providing answers to three fundamental questions, namely, whom to treat, when to treat, and how to treat. Both common ground and different approaches exist among them. General preventive measures should start along with GC initiation, and the duration of GC therapy should be limited to the minimal effective range. A pre-existing fracture, age, gender, menopausal status, dose, and duration of GC treatment are key factors in the decision to initiate antiosteoporotic medication. Oral bisphosphonates are typically regarded as the first-line treatment choice for GIOP partly due to their cost-effectiveness. Denosumab is another valid option, but an "exit strategy" should be considered before its initiation due to the risk of rebound-associated vertebral fractures upon its discontinuation. Since impaired bone formation represents the main mechanism by which GCs negatively affect skeletal health, osteoanabolic therapies appear to be pathophysiologically the more appropriate and appealing option, although cost considerations currently limit their use to selected severe cases. Regardless of the agent selected to mitigate the impact of GCs on the skeleton, what is most crucial is that the treating physician correctly stratifies the risk and intervenes at the right time.

Calcipotriol and Betamethasone Dipropionate Cream Based on PAD Technology for the Treatment of Plaque Psoriasis: A Narrative Review.

Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) represents the first-line choice in topical psoriasis treatment. A CAL/BDP cream based on polyaphron dispersion (PAD) Technology has emerged as a novel formulation for a more convenient topical treatment of psoriasis. This article aims to summarize the most relevant published evidence about CAL/BDP PAD-cream and its underlying PAD Technology. The PAD Technology enables CAL and BDP stability in an aqueous cream through a multimolecular shell structure, as well as it increases the penetration of both active ingredients into the epidermis and dermis. This technology also demonstrated to increase the cosmetic acceptability and to provide the desirable sensory properties for a topical psoriasis treatment. Two phase III clinical trials have been conducted so far with CAL/BDP PAD-cream. Findings from both trials revealed high efficacy with a fast onset of action, a favourable safety and tolerability profile and convenience for CAL/BDP PAD-cream compared to CAL/BDP gel. In the trial including patients with psoriasis affecting the scalp (MC2-01-C7), results support the use of CAL/BDP PAD-cream in scalp psoriasis. An anchored matching-adjusted indirect comparison (MAIC) was conducted to compare CAL/BDP PAD-cream and CAL/BDP foam, as both products had been previously compared to CAL/BDP gel. CAL/BDP PAD-cream and CAL/BDP foam showed equivalent efficacy and quality of life at their recommended treatment duration, whereas greater treatment satisfaction for CAL/BDP PAD-cream was found after one week of treatment. Overall, the high patient acceptability and treatment satisfaction observed with CAL/BDP PAD-cream in clinical trials may lead to improved adherence and hence higher efficacy in clinical practice.

E08 Single center study of Systemic Juvenile Idiopathic Arthritis in Moroccan patients

Abstract Introduction Juvenile idiopathic arthritis (JIA) is the most common rheumatological disorder in childhood. About 10% to 20% of children with JIA have a rare and serious subtype called systemic juvenile idiopathic arthritis (SJIA). SJIA differs from other subtypes in that it’s the only one considered an autoinflammatory rather than autoimmune disease because of the association with systemic features and is therefore treated differently with anti-IL1 and anti-IL6. Objectives To describe epidemiological data of SJIA in Moroccan patients taking into account environmental conditions. To compare existing criteria (ILAR, Fautrel, Yamaguchi) to the new Pediatric Rheumatology International Trials Organization (PRINTO) classification currently in the process of validation. Patient and methods Retrospective prospective study conducted between January 2019 and December 2022. SJIA was diagnosed based on one of the four classification criteria ILAR, Fautrel, Yamaguchi or PRINTO Classification after ruling out infectious disease, immunodeficiency and malignancy whenever necessary. Complete remission was defined as the absence of clinical signs and inflammatory syndrome. Partial remission was defined as the absence of active clinical signs with persistence of inflammatory syndrome. Results Nine SIJA (44% male) patients were enrolled. The mean age at diagnosis was 4 years 8 months, the mean time to diagnosis was 4.8 months (range 1 – 24 months), the average follow up period was 16.4 months. At the time of diagnosis, the most common findings were typical fever (100%), arthritis (66%), skin rash (55%), 2 patients had pericarditis and one had macrophage activation syndrome (MAS), there was no renal or pulmonary involvement. Laboratory data showed in all patients, high level of C-reactive protein at mean value of 183 mg/l, increased erythrocyte sedimentation rate at mean of 88 mm first h, hyperleukocytosis at mean of 17 000 WBC/mm3 with high neutrophil counts at a mean of 12 297/mm3 and thrombocytosis at a mean of 625 000/mm3. To rule out other diagnosis, para clinical evaluation showed a positive antinuclear antibody in one patient without pathogenic significance, a bone marrow count performed in 3 patients, showed normal count in 2 patients and hemophagocytosis in one patient and immunoglobulins assay performed in 3 patients was normal. Of the 9 patients, 4 met all the criteria, 2 were diagnosed based on Yamaguchi criteria and one on Fautrel criteria, one fulfilled all criteria except ILAR and the last fulfilled only ILAR and new PRINTO classification. One patient was treated with corticosteroid pulse therapy for MAS and then oral corticosteroids with complete remission. Another received corticosteroids and biotherapy [tocilizumab (TCZ)] upfront due to late consultation and severe form with complete remission. Seven patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) of which one achieved partial remission with a delay of 2 months of follow up and 6 required adjunctions of another medication: corticosteroids (4), MTX (2), biotherapy (5) [anakinra (5), Switch TCZ (2)] with complete remission. The last patient reached complete remission under corticosteroids, Triamcinolone Hexacetonide knee infiltration and methotrexate. Anakinra was the most common first-line biologic treatment choice (n = 5), and 2 of them need switch to Tocilizumab to achieve remission. One of the 2 patients with pericarditis needed a rescue drainage. Outcome was favorable in all patients except one who had a relapse with final remission, and articular sequel in 3 patients. Discussion and conclusion SJIA is a rare but serious condition with high risk of morbidity related to arthritis and mortality from MAS and pericarditis. The latter features turn into a good prognosis with early diagnosis and treatment, as we have done. It can occur any time during childhood, but it most commonly starts at around the age of two years, unlike our patients who were older. No predominance ratio is reported as we have noted. SJIA is referred to as Still disease by some authors justifying the new PRINTO classification and the specific treatment. In our study, Yamaguchi criteria seem to be the most sensitive (7/9 fulfilled) followed by New PRINTO classification and Fautrel criteria (6/9 fulfilled), ILAR criteria are the less sensitive (5/9 fulfilled) what can delay diagnosis and treatment. Our study showed the benefit of biological agent, 66% of patients achieved remission with at least one biological agent and we concluded that Anti-IL1 drugs are mostly preferred for ongoing systemic inflammation. However Anti-IL-6 agents are very efficient in patients with a polyarticular course.