Side Effect Profile Research Articles

Colchicine prevents post-ablation atrial fibrillation recurrence: a systematic review and meta-analysis

Abstract Background Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure with appreciable effectiveness; however, post-AF ablation recurrence is often observed. The pathophysiology behind this recurrence is often inflammation and oxidative stress triggered during the ablation procedure. Colchicine is a potent anti-inflammatory agent that has emerged as a promising therapeutic for preventing post-ablation AF recurrence; however, the data available on its efficacy are limited. Purpose This meta-analysis aimed to investigate the outcomes of post-ablation AF patients who received colchicine in the postoperative period. Methods A comprehensive literature search spanning major bibliographic databases was conducted to retrieve studies comparing outcomes in post-ablation AF patients who received colchicine versus those who did not. The outcomes of interest included AF recurrence, pericarditis, gastrointestinal side effects, and hospitalization. AF recurrence was determined with a 12-lead electrocardiogram and/or Holter monitoring. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were pooled from all studies using the DerSimonian and Laird random-effects model. Statistical significance was set at p ≤ 0.05. Results Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up [OR: 0.62; 95% CI: 0.48, 0.79; p=0.0001] but had higher gastrointestinal side effects [OR: 2.67; 95% CI: 1.00, 7.12; p=0.05]. There were no statistically significant differences in acute pericarditis [OR: 0.54; 95% CI: 0.27, 1.05; p=0.07] or hospitalization [OR: 1.03; 95% CI: 0.73, 1.45; p=0.87]. Conclusion Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects such as diarrhea and nausea. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in the prevention of AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.

Obinutuzumab as a viable therapeutic strategy in rituximab-refractory childhood frequently relapsing, steroid-dependent nephrotic syndrome that relapsed during B-cell depletion.

A subgroup of children with frequently-relapsing, steroid-dependent nephrotic syndrome relapse during B-cell depletion after rituximab. A 15-year-old boy with focal segmental glomerulosclerosis became rituximab-refractory after 5 courses of treatments, with a relapse-free period shortened to 1month. Circulating total and memory B-cells were undetectable at the time of relapse. A single infusion of obinutuzumab sustained relapse-free remission up to the last follow-up at 18months. There was persistent hypogammaglobulinemia but no infection was observed. Obinutuzumab may be a viable option for attaining long-term remission with reasonable side effect profiles in patients who relapse during B-cell depletion after rituximab.

Systematic Review: Comparative Efficacy and Safety of Losartan vs. Candesartan for the Treatment of Hypertension

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease (CVD) and remains a leading cause of morbidity and mortality globally. Effective management of hypertension is essential for preventing comp lications such as stroke, myocardial infarction, and heart failure. Angiotensin II receptor blockers (ARBs) like losartan and candesartan are well-established therapeutic options for blood pressure (BP) control and are widely prescribed due to their favorable side-effect profiles and organ-protective properties. Despite being members of the same drug class, these ARBs differ in their pharmacokinetics, receptor binding affinity, and clinical efficacy. This systematic review aims to provide a detailed comparison of the efficacy and safety of losartan versus candesartan in managing hypertension. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases, retrieving studies published from 2000 to 2024 that compared the two ARBs directly in hypertensive populations. A total of 25 randomized controlled trials (RCTs) and observational studies, comprising more than 12,000 participants, were included in the analysis. The primary outcomes evaluated were the reduction in systolic and diastolic blood pressure, cardiovascular event prevention, and adverse event profiles. The results suggest that both losartan and candesartan effectively lower BP, but candesartan consistently demonstrated greater reductions in both systolic and diastolic BP compared to losartan. Candesartan also appeared to have superior cardiovascular outcomes, with a lower incidence of major cardiovascular events such as stroke, myocardial infarction, and heart failure hospitalizations. The safety profiles of both drugs were comparable, though losartan was associated with a slightly higher incidence of cough and discontinuation due to adverse events. Overall, candesartan may offer a slight clinical advantage over losartan, particularly in patients requiring more potent or sustained BP control. However, both drugs remain valuable options in the management of hypertension. Further long-term studies are recommended to confirm these findings and to investigate the potential benefits of each drug in specific patient subgroups.

Advancing ketamine in the treatment hierarchy for refractory depression.

Evidence indicates that ketamine is highly effective, has a lower side effect profile and is better tolerated compared to many augmentation strategies for refractory depression. This, combined with data on psychiatric treatment outcome mediators, suggests that earlier intervention with ketamine could improve outcomes for patients suffering from refractory depression.

Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review.

Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.

Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma

BackgroundIncorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin’s lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin’s lymphoma, including in preliminary studies involving previously untreated patients.MethodsWe conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin’s lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause.ResultsOf 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P=0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation.ConclusionsN+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin’s lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.)

Clinical and molecular epidemiology of malignant salivary gland tumors

Salivary gland carcinomas are a rare and heterogeneous group of malignant tumors, accounting for 3-6% of all malignant tumors in the head and neck region. The 1-, 3- and 5-year survival rates are 83%, 69% and 63% respectively. Due to new molecular pathological and genetic findings, new entities are constantly being defined as part of the recurring WHO classification of salivary gland carcinomas, so that the incidence rates of the entities are subject to constant change. The only certain risk factor for the development of salivary gland carcinomas is ionizing radiation. In addition, large tumors, cervical lymph node involvement and perineural sheath involvement significantly worsen the prognosis. Today, molecular pathology is coming to the fore, with which potential targets have been identified that can offer prognosis-improving treatment options, particularly in recurrent or distant metastatic stages. Entity-specific tyrosine kinase inhibitors such as axitinib in adenoid cystic carcinoma or larotrectinib in secretory carcinoma and cross-entity therapies such as HER2 inhibition and androgen deprivation can prolong median and progression-free survival with a favorable side effect profile.

Gynaecomastia revealing amiodarone-induced hypergonadotropic hypogonadism: an overlooked complication?

We report a case of primary hypogonadism induced by amiodarone and review the relevant literature. Amiodarone has a well-established and extensive profile of side effects including thyroid toxicity, corneal deposits and skin discoloration. In rare cases, epididymitis or orchitis may occur. This inflammation can lead to testicular atrophy, inducing primary hypogonadism. We present the case of a 57-year-old patient, treated with amiodarone for several years, initially presenting with testicular pain followed by gynaecomastia, and finally loss of libido indicative of hypergonadotropic hypogonadism. Imaging confirmed bilateral testicular atrophy. Amiodarone was discontinued, and androgen replacement therapy was initiated. This case, combined with data from the literature, highlights the importance of careful monitoring of patients on amiodarone to identify symptoms or clinical signs suggesting testicular dysfunction, to diagnose and treat consequent hypogonadism.

The Most Common Side Effects, Concerns and Discontinuation Patterns of Oral Contraceptive Pills Among Polish Women: A Cross-Sectional Study.

Over the decade, variety and effectiveness of contraception methods have greatly improved, resulting in increased popularity of oral contraceptive pills (OCPs). However, hormonal contraception carries the risk of multiple side effects. The lack of sufficient knowledge often leads to the development of health concerns, which can affect patient's adherence. The aim of our research was to describe a side effect profile of OCPs and assess the most frequent concerns and discontinuation reasons in Polish women. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. This cross-sectional study was based on a survey, which was distributed online and open from 29 April to 15 May 2022. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. Out of 1699 respondents, the current OCPs intake was reported by two thirds of women and 22% had a history of using them in the past. Seventy-nine percent of all OCPs users experienced adverse effects while 9% reported having concerns about safety and potential adverse effects. Decreased libido and weight gain were the most significant reasons for ceasing hormonal contraception. Moreover, the most common concerns and the most unfavorable side effects varied in different age groups. The occurrence of anxiety depended on age and education. Healthcare professionals prescribing OCPs should provide their patients with comprehensive counseling. Understanding and addressing concerns of young women can improve their compliance and reduce the number of unintended pregnancies.

Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.

Background: Individuals with Duchenne muscular dystrophy (DMD) have increased risk of obesity from prolonged glucocorticoid use and progressive muscle weakness. Over 50% have obesity by the teenage years. Objectives: The current study examines literature on obesity management in DMD and describes how obesity pharmacotherapy can be used in this high-risk cohort. Methods: This review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A Pubmed Database search was conducted from January 2000 to May 2024. Included terms were DMD and topiramate, phentermine, metformin, glucagon-like peptide-1 receptor agonist, semaglutide, and liraglutide. Eligible studies were cataloged to examine obesity pharmacotherapy, side effect profiles, and clinical outcomes. Results: Twenty studies met inclusion criteria, 18 on metformin. Reviewed studies varied in duration from 4 to 24 weeks, ages 6.5-44 years old, with 112 participants total (range: 1-30 participants). Included studies were: eight animal studies, six clinical trials, four reviews, one cohort study, and one case report. Primary outcomes varied among studies: muscular degeneration and function (15 articles), cardiac function (2 articles), weight loss (2 articles), and general endocrine care (1 article). Conclusions: Adjunct obesity pharmacotherapy use in youth with DMD is promising but needs to be confirmed. Large gaps include appropriate agent selection, side effect monitoring, and dose escalation. The overall quality of pediatric-specific evidence for the use of obesity pharmacotherapy in youth with DMD is low. Future research is needed to investigate how to safely utilize these agents.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review.

Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate). We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

The Androgen Deprivation Therapy Landscape in 2024 – Co-navigating the Available Options with Prostate Cancer Patients

This symposium convened during the 2024 European Association of Urology (EAU) Congress in Paris, France, focusing on the multifaceted aspects of prostate cancer (PCa) treatment from the patient’s perspective. The session delved into the nuanced needs, expectations, and treatment experiences encountered by individuals diagnosed with this condition. A pivotal aspect of the discussion centred on the imperative of ensuring patient awareness and informed consent, particularly concerning androgen deprivation therapy (ADT), given its array of potential side effects. ADT, a cornerstone in advanced PCa management, encompasses a spectrum of side effects including both physical and psychological dimensions. These include, but are not limited to, body hair loss, weight fluctuations, mood alterations, decreased libido, cognitive impairments, muscle atrophy, and bone density loss. Effective management of these side effects requires comprehensive support to be provided to patients to mitigate complications and optimise quality of life. The options for ADT were discussed, with their comparative strengths and challenges. ADT strategies take effect over different time periods (from 12 hours up to 4 weeks), exert varying effects on testosterone levels, and carry different side effect profiles. Selecting the optimal course of treatment for localised or locally advanced PCa requires consideration of whether the patient is at intermediate-, high-, or very high-risk of biochemical recurrence, and whether the intermediate-risk disease is classified as favourable intermediate-risk (FIR) or unfavourable intermediate-risk (UIR). While continuous ADT is the standard of care, intermittent ADT has been associated with significantly better quality of life scores for hot flushes, desire for sexual activity, and urinary symptoms, with a trend toward improvement in the level of fatigue. Furthermore, the interplay between PCa, ADT, and cardiovascular disease (CVD) was discussed to underscore the imperative for clinicians to assess the cardiovascular risks associated with ADT, particularly in patients with heightened cardiovascular vulnerability. Mitigating the adverse skeletal effects of ADT mandates a multifaceted approach encompassing nutritional supplementation, exercise regimens, and lifestyle modifications including alcohol cessation and smoking cessation. Integrating a prehabilitation checklist into clinical practice emerges as a pragmatic strategy to facilitate informed discussions regarding the potential adverse effects of ADT, enabling proactive support provision to optimise patient outcomes.

The Role of Gut Microbiota in the Efficacy and Side Effect Profile of Biologic Therapies for Autoimmune Diseases

The Role of Gut Microbiota in the Efficacy and Side Effect Profile of Biologic Therapies for Autoimmune Diseases

Cancer-Related Lymphedema and Psychological Distress.

Cancer-related lymphedema (CRL) places an already vulnerable patient population at risk for the development and worsening of psychological distress. The purpose of this review is to highlight factors contributing to distress in lymphedema secondary to breast, head and neck, genitourinary cancers, and melanoma and discuss pertinent treatment considerations. Multiple factors contribute to distress in CRL, including changes in body image, sleep, sexuality, functional capacity, and social interaction. There is limited literature describing psychopharmacological considerations in CRL, though exercise, which may be used for the treatment of depression and anxiety, may also improve CRL. Psychiatrists, oncologists, physiatrists, palliative medicine physicians, and physical and occupational therapists should have an awareness and understanding of CRL. To effectively manage distress in these patients, it is crucial to be mindful of psychotropic side-effect profiles, emphasize non-pharmacologic modalities including psychotherapy and exercise, and ensure patients receive evidence-based treatments for CRL.

Semaglutide in patients with kidney failure and obesity undergoing dialysis and wishing to be transplanted: A prospective, observational, open-label study.

Chronic kidney disease (CKD) and obesity are major global health challenges, eventually leading to kidney replacement therapy (KRT), but body mass index (BMI) thresholds hinder kidney transplantation. Glucagon-like peptide-1 receptor agonists induce weight loss, thereby offering attractive treatment options; however, their safety and efficacy have not been systematically investigated in patients undergoing dialysis. We conducted a prospective 12-week, open-label trial with 13 patients who had a BMI ≥ 30.00 kg/m2, were undergoing dialysis (12 haemodialysis and 1 peritoneal dialysis) and had not been listed for transplantation due to their weight. Semaglutide was administered once weekly subcutaneously, and the dose was increased from 0.25 mg to 0.5 mg and then to 1 mg. Study endpoints included change in body weight and BMI (primary - statistically evaluated by repeated measures analysis of variance [ANOVA]), side effects, adverse events, blood parameters and patient-reported outcomes (secondary). At baseline, the mean age ± standard deviation of patients was 64.0 ± 6.4 years, the mean weight was 113.9 ± 16.6 kg, and the mean BMI was 37.3 ± 3.9 kg/m2. At week 12, average weight reduction under semaglutide treatment was 4.6 ± 2.4 kg and ranged from 2.0 to 9.7 kg (p < 0.001 for weight and BMI reduction across the study period). One patient discontinued treatment due to nausea/vomiting, two patients died of unrelated causes and six patients reported side effects. Approximately 9 months after the treatment started, three patients were able to seriously reconsider being listed for transplantation. Semaglutide treatment resulted in significant reduction in weight and BMI in patients with obesity undergoing dialysis, while maintaining an acceptable side effect profile comparable to that of the non-dialysis population.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

8114 The Need For Autoantibody Screening And Diagnostic Criteria For Immune-Checkpoint Inhibitor-Induced Type 1 Diabetes

Abstract Disclosure: A. Gupta: None. H. Sanekommu: None. A.B. Ravin: None. M. Akula: None. J. Cheng: None. Background: Immune-checkpoint inhibitors (ICIs) such as Nivolumab have been extensively studied, especially in relation to their side-effect profiles. Patients on Nivolumab are prone to immune-related adverse events (irAEs) including type 1 diabetes mellitus, thyroiditis, and hypopituitarism. Prior studies have indicated that ICIs can unmask existing diabetic autoimmunities, but currently no specific guidelines exist for autoantibody screening prior to initiating treatment. We report a unique case of a young patient with newly diagnosed immune-checkpoint inhibitor-induced type 1 diabetes (ICI-T1DM) who was found to have mixed autoantibody results. Clinical Case: This is a 31-year-old male who was diagnosed with fibrolamellar hepatocellular carcinoma (pT23N0) and underwent partial hepatic resection later that year. Repeat imaging showed new hepatic lesions, thus Nivolumab was initiated. He received a total of three cycles, after which he presented to the hospital with symptoms of fever and nausea; labs were consistent with diabetic ketoacidosis (DKA) for which he was treated with IV insulin and aggressive hydration with successful resolution. Nivolumab was stopped and the patient was discharged on a basal-bolus insulin regimen. Further outpatient workup was significant for A1c 5.9% (n&amp;lt;5.7%), C-peptide (with glucose 220mg/dL) 0.7 (n=0.8-3.9ng/mL), glutamic acid decarboxylase autoantibody (GAD Ab) 11 (n&amp;lt;5.0U/mL). Insulin antibody and islet cell antibody IgG were negative. Due to the acute onset in the presentation and the recent use of Nivolumab, the patient was diagnosed with ICI-T1DM. He remained insulin-dependent after discharge. Unfortunately, soon after, he began showing signs of liver failure and ultimately underwent liver transplantation. Conclusion: This case highlights two crucial aspects - the importance of screening for autoantibodies prior to initiating an ICI and the necessity for guidelines in diagnosing ICI-T1DM. Given the evidence linking positive GAD Ab to a higher risk of developing DKA and earlier onset ICI-T1DM, it is beneficial to screen patients for these autoantibodies prior to ICI initiation to identify those more susceptible to developing ICIDM1. It may also be beneficial to obtain a C-peptide level prior to initiation to evaluate for endogenous insulin production. Additionally, while several factors support the diagnosis of ICI-T1DM such as recent ICI use, acute DKA presentation, low C-peptide levels, and the need for exogenous insulin, there is currently no specific criteria for the formal diagnosis of ICI-T1DM. Consequently, the decision to continue an ICI remains uncertain until specific diagnostic criteria are established for healthcare providers. Presentation: 6/2/2024

7959 Combination Therapy Of Multi-Targeted Tyrosine Kinase Inhibitors And Immune Checkpoint Inhibitors In Advanced Adrenocortical Carcinoma

Abstract Disclosure: F. Yaylaci Mert: None. V. Balderrama Brondani: None. L.P. Marcal: None. M. Campbell: None. C. Jimenez: None. J. Varghese: None. A. Shah: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare cancer with limited response to systemic chemotherapies. Monotherapy with multi-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in ACC patients has limited efficacy. Combining TKIs with ICIs increased response rates in other malignancies but the efficacy of this approach in ACC is still unknown. This retrospective study aims to evaluate the efficacy and safety of the combined use of TKIs and ICIs in patients with advanced ACC. Methods: A single-center, retrospective cohort study in patients with advanced ACC treated with the combination of TKIs and ICIs. Response rates, progression-free survival (PFS), overall survival (OS) calculated from the time of combination, disease control rate (DCR), and safety profile were the main study objectives. Results: Seventeen patients were treated with combination therapy of TKI (lenvatinib or cabozantinib) and ICI (pembrolizumab) between January 2017 and December 2023. Eleven patients were women, the median age was 43.4 years (range 21.9-66.6), and 8 (47.1%) patients presented cortisol-producing tumors. All patients had prior systemic therapy, median of 3 (range 1-9) lines of therapy. The median duration of TKI+ICI therapy was 7.1 months (range 0.7-69.7). The treatment was discontinued in one patient due to a grade 3 adverse event (gastrointestinal fistula) after 1.6 months of treatment. Best overall responses were as follows: partial response 2 (13%), stable disease 8 (53%), and progressive disease 5 (34%). DCR was 58.8%. Median PFS was 7.1 months (range 0.7-66.4). One death occurred during the study due to disease progression. The median OS was 21.3 months (range 3.3-70.3). At the time of this report, 7 patients (41%) were still alive. Conclusion: The combined use of TKIs and ICIs in heavily treated ACC patients is associated with occasional durable responses and has a predictable and manageable side effect profile. This combination is worthy of a prospective clinical trial to validate the findings and establish new lines of therapy for this rare disease. Presentation: 6/2/2024

7784 Perspectives Of Anabolic Steroid Users On Steroid Use, Side Effects, And Patient Education

Abstract Disclosure: D.D. Lam: None. M. Potemkin: None. J. Kreutz: None. H. Shah: None. P. Patel: None. P.K. Doyle-Baker: None. Background: Details on first-hand perceived and experienced effects of anabolic steroids (AS) on users are sparse. Furthermore, there is limited information on what type of AS knowledge users possess, irrespective of current published works in AS pharmacology. This study aimed to identify insights of AS users regarding their knowledge and patterns of AS use, commonly experienced side effects, sources used for steroid education, and their unique needs as a population. Study Design: AS users from Calgary, Alberta, Canada of various sexes and ages ≥ 18 were recruited through gyms in Alberta with convenience and snowball sampling techniques. Participant-centered-qualitative research using semi-structured interviews was conducted. Participants discussed their experiences as a user and shared their understanding of AS, details of usage including compounds used, and their commonly experienced or perceived side effects through one-on-one interviews of varying durations. Interviews were coded using NVivo 14 Software prior to thematic analysis. Resulting codes were organized into overarching themes based on researchers' consensus. Results: Seven AS users were confidentially interviewed over Zoom. Several important themes emerged. There existed a wide variety of AS that users have identified, with some of the most commonly mentioned being Anavar, Nolvadex, Testosterone, and Trenbolone. Steroid users frequently identified increased strength with faster recovery from training and better overall appearance as prominent advantages of AS use. Conversely, hair loss, gynecomastia, acne, aggression, erectile dysfunction, altered libido, hypogonadism, infertility, and injection related discomfort were commonly identified disadvantages of AS use. Lastly, individuals using AS report having consulted many different sources to learn about appropriate dosing, techniques, and side effects. These sources ranged from peers, coaches, online forums, social media, and scientific research articles, but rarely included healthcare professionals. Conclusions: This study identified the need for education and research in exploring the impact of AS use. A variety of AS exist on the market, yet information pertaining to the side effect profiles of these AS from a patient’s perspective is lacking and exploration of this topic is warranted. Further investigation as to the impact of user education on their understanding of the risks versus the benefits of AS use must also be conducted. Presentation: 6/1/2024