Einstein Medical Center Montgomery

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily affecting joints. Methotrexate (MTX) and hydroxychloroquine (HCQ) are common disease-modifying antirheumatic drugs, yet more comparative outcome studies are needed. This study aimed to compare associations of HCQ versus MTX initiation with mortality, cardiovascular events, and other major health outcomes in RA patients. This retrospective cohort study utilized the TriNetX database (electronic health records from 142 global health care organizations) to compare selected 10-year outcomes in RA patients starting HCQ or MTX therapy.Methods:Patients aged 18–75 years diagnosed with RA (ICD-10 codes) were studied. This retrospective, multi-center cohort study used data from the TriNetX Research Network (analysis: 23 March 2025). Two cohorts, HCQ initiators and MTX initiators, were created. Propensity score matching (PSM) balanced cohorts for age, sex, race, pre-specified comorbidities, and concomitant medications. Primary outcomes were 10-year cumulative incidences of all-cause mortality, non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), pulmonary hypertension (PAH), end-stage renal disease (ESRD), interstitial lung disease (ILD), osteoporosis, and Alzheimer’s dementia.Results:After PSM, 56 362 patients were in each cohort. HCQ initiation was associated with significantly higher 10-year relative risks (RR) for NSTEMI (RR: 1.217), ESRD (RR: 2.624), ILD (RR: 1.377), PAH (RR: 1.625), and all-cause mortality (RR: 1.379) compared to MTX. No statistically significant RR differences were observed for Alzheimer’s dementia, STEMI, or osteoporosis.Conclusion:In this large, real-world observational study, RA patients initiating HCQ had a higher 10-year risk association for ESRD, ILD, PAH, NSTEMI, and all-cause mortality versus MTX initiators. These findings highlight potential differences in systemic risk profiles and are hypothesis generating. However, the results must be interpreted with significant caution due to major limitations, including the potential for residual confounding from unmeasured variables like disease severity and the absence of adherence data. Further prospective research that addresses these limitations is warranted to confirm these associations and explore underlying mechanisms.

Disclosure: R. Devbhandari: None. S. Tripathee: None. H. Akbari: None. M. Shah: None. A. Kang: None. R.M. Jhingan: None.Introduction: Amiodarone, a potent antiarrhythmic, is highly effective for rate control in atrial fibrillation (AF), particularly in hemodynamically unstable patients. Amiodarone-induced thyrotoxicosis occurs in 3-10% of cases due to iodine-induced hormone synthesis and follicular cell toxicity. We report a case of thyroid storm with AF, where thyroid function improved despite IV amiodarone use. Case report 34-year-old non-verbal male with Friedreich’s ataxia, quadriplegia, and paroxysmal AF presented with tachycardia and fever. On arrival, he was tachycardic with low normal blood pressure. The electrocardiogram showed atrial fibrillation. Initial labs were unremarkable. Computed tomography (CT) scan didn’t reveal any pulmonary embolism or cardiopulmonary abnormalities but raised suspicion for cholecystitis. He soon developed AF with rapid ventricular response with heart rates 200-250 bpm, refractory to IV metoprolol, and two rounds of synchronized cardioversion. He was started on IV esmolol and digoxin. Due to persistent tachycardia and hypotension precluding diltiazem use, an IV amiodarone drip was started as per cardiology recommendation. Phenylephrine was started for inotropy due to its negative chronotropic effect. The thyroid function panel revealed TSH <0.01 mIU/L (0.35-4.94), FT4 2.82 ng/dL (0.7-1.48), and T3 53.17 ng/dL (35-193). He had no prior history of thyroid disorders and CT imaging showed no thyroid abnormalities. He was suspected to have new onset hyperthyroidism with thyrotoxicosis. He subsequently developed septic shock secondary to acute acalculous cholecystitis confirmed on a hepatobiliary iminodiacetic acid scan. Echocardiography was unremarkable. Thyroid storm was suspected in the setting of acute cholecystitis and a Burch-Wartofsky score of 65. He was treated with IV hydrocortisone, oral methimazole, IV fluids, and antibiotics which along with percutaneous cholecystostomy led to hemodynamic improvement. Hydrocortisone was tapered with the continual improvement of FT4, and methimazole was continued for new-onset hyperthyroidism, with outpatient follow-up planned for further workup. Conclusion: This case highlights the potential use of IV amiodarone in thyroid storm for refractory arrhythmia despite maximal conventional management without worsening of thyrotoxicosis, as the patient’s thyrotoxic symptoms and thyroid function improved despite IV amiodarone. IV amiodarone inhibits peripheral T4 to T3 conversion which in combination with anti-thyroid medications, preferably started before amiodarone to suppress new hormone synthesis, may help control thyrotoxicosis symptoms in the short term. However, data remain limited due to the absence of randomized controlled trials and their known thyrotoxic properties, for which further investigation is warranted.Presentation: Sunday, July 13, 2025

Abstract Disclosure: A. Kang: None. H. Akbari: None. R. Devbhandari: None. R.M. Jhingan: None. Drug-induced thyroiditis is characterized by inflammation of the thyroid gland which requires discontinuation of the offending agent and close clinical monitoring. Ruxolitinib is an antineoplastic agent that is used to treat myelofibrosis and works by inhibiting janus kinase (JAK) receptors. To our knowledge, this is the first case of ruxolitinib associated thyroid dysfunction in myelofibrosis. Our patient was a woman in her 70s with a history of JAK2 myelofibrosis, portal hypertension and no prior history of thyroid disease who was admitted to the hospital for an upper gastrointestinal bleed secondary to esophageal varices. Her clinical course was complicated by hypotension, bradycardia, hypothermia which prompted evaluation of the thyroid. Labs were significant for thyroid stimulating hormone 11.03, free T4 &amp;lt; 0.42. She had been experiencing fatigue and cold intolerance for the past week and had been taking a new medication ruxolitinib for the past 6 weeks for myelofibrosis. Her family confirmed that she did not have any personal or family history of thyroid disorders. Previous imaging studies were unremarkable for thyroid pathology. She also did not have any recent medication changes apart from the addition of ruxolitinib. Ruxolitinib was discontinued and the patient was treated with intravenous levothyroxine and hydrocortisone with appropriate improvement of labs and clinical features. Thyroiditis is not a known adverse effect of ruxolitinib, but other tyrosine kinase inhibitors such as sunitinib have been reported to induce either hypothyroidism or hyperthyroidism. Among reported cases, thyroid dysfunction typically developed in the time frame of 1-2 months which is consistent with our patient’s timeline of symptoms. Ruxolitinib is currently being evaluated for its role in anaplastic thyroid cancer. In a recent study, JAK1/2-STAT3 receptors were observed to be upregulated in anaplastic thyroid carcinoma compared to normal thyroid and papillary thyroid cancer tissues. Ruxolitinib suppresses the phosphorylation of STAT3 which ultimately results in mitochondrial deficiency and impaired cell division. In vitro and vivo administration of ruxolitinib resulted in significant apoptosis of the tumor cells. Regarding our patient, it is plausible that inhibition of the JAK1 and JAK2 pathway in thyroid hormone metabolism could have contributed to her presentation. Much remains to be elucidated on the long-term implications of JAK inhibitors such as ruxolitinib, and ongoing research is imperative to substantiate the safety and efficacy of their use in thyroid disease. Presentation: Saturday, July 12, 2025

Positron emission tomography (PET) has become a powerful tool in Alzheimer’s disease (AD) research by enabling in vivo visualization of pathological biomarkers. Recent efforts have aimed to integrate PET-derived imaging phenotypes with genome-wide association studies (GWASs) to better elucidate the genetic architecture underlying AD. This systematic review examines studies that leverage PET imaging in the context of GWASs (PET-GWASs) to identify genetic variants associated with disease risk, progression, and brain region-specific pathology. A comprehensive search of PubMed and Embase databases was performed on 18 February 2025, yielding 210 articles, of which 10 met pre-defined inclusion criteria and were included in the final synthesis. Studies were eligible if they included AD populations, employed PET imaging alongside GWASs, and reported original full-text findings in English. No formal protocol was registered, and the risk of bias was not independently assessed. The included studies consistently identified APOE as the strongest genetic determinant of amyloid burden, while revealing additional significant loci including ABCA7 (involved in lipid metabolism and amyloid clearance), FERMT2 (cell adhesion), CR1 (immune response), TOMM40 (mitochondrial function), and FGL2 (protective against amyloid deposition in Korean populations). The included studies suggest that PET-GWAS approaches can uncover genetic loci involved in processes such as lipid metabolism, immune response, and synaptic regulation. Despite limitations including modest cohort sizes and methodological variability, this integrated approach offers valuable insight into the biological pathways driving AD pathology. Expanding PET-genomic datasets, improving study power, and applying advanced computational tools may further clarify genetic mechanisms and contribute to precision medicine efforts in AD.

Statins, commonly used for hyperlipidemiaand more importantly having proven efficacy in lowering cardiovascular risk, are a very popular class of medications. Side effects are usually mild, and the class as a whole is generally well-tolerated by patients. However, one rare and more serious side effect is statin-induced autoimmune necrotizing myopathy. A 65-year-old woman with a past medical history of hyperlipidemia on atorvastatin for four years, type 2 diabetes, sciatica, and a prior history of endometrial cancer, presented to the emergency department due to proximal muscle weakness worsening over 2-3 months. On labs, her aspartate transaminase (AST) andalanine transaminase (ALT)were both elevated at 344 and 244, respectively. Additionally, creatine kinase(CK) was 13,000,C-reactive protein(CRP)was 42, and aldolase was 80.4. She was antinuclear antibody (ANA) negativebut found to be anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase (HMGCR ab) positive. Her magnetic resonance imaging (MRI) showed significant edema in bilateral thighs. During her hospital course, she was started on prednisone, fluids, and intravenous immunoglobulin(IVIG). Once completing two days of IVIG, the patient was discharged to rehab with rheumatology follow-up. The purpose of this case is to elucidate a rare side effect of a medication despite being on it for several years and to increase awareness and attention to an adverse effect that may one day lead to stratifying patients' risk on the medication.

Background:Vertebral fractures are the most common of all osteoporotic fractures, the risk of which increases with age. Bone density begins to decrease after age 40, with more decline in postmenopausal women. Caucasian women are particularly at increased risk. Whether symptomatic or asymptomatic, vertebral fracture can affect patients’ health and quality of life. A bone density scan is important for diagnosing underlying osteoporosis, which increases the risk of recurrent fractures.Objectives:In our observational, retrospective cohort study, we aimed to compare the rates of osteoporosis diagnosis, bone density scans, and treatment between male and female cohorts with vertebral fractures but no prior osteoporosis diagnosis. This study was conducted using the TriNetX database, which encompasses electronic health records from >80 diverse global healthcare organizations.Methods:Two cohorts were established using the TriNetX database: women (Cohort 1) and men (Cohort 2). We included patients aged 55 years and above in both groups. The index event was the initial appearance of a vertebral fracture diagnosis, using the International Classification of Diseases, Tenth Revision (ICD-10) codes. We excluded patients who had osteoporosis fractures prior to the vertebral fracture. Propensity score matching was employed for age and race/ethnicity. Our outcome of interest included osteoporosis diagnosis, the occurrence of bone density scans, and osteoporosis treatment within three years of the index event (vertebral fracture). The studied osteoporosis treatments included bisphosphonates, denosumab, romosozumab, teriparatide, abaloparatide, and raloxifene. We used measures of association to calculate the risk and risk ratio showing the difference in the occurrence of outcomes in patients with vertebral fracture.Results:The analysis involved 194,638 women and 112,067 men with vertebral fractures. The age at the time of vertebral fracture was slightly different between the two cohorts. Both groups consisted primarily of a white population. After propensity score matching, 108,718 patients from each group were included in the analysis. 20.128% of women (compared to 10.538% of men) were diagnosed with osteoporosis within 3 years of vertebral fracture diagnosis, with a risk difference of 9.59% and a risk ratio of 1.91 (95% CI: 1.862, 1.96; P < 0.0001).[Figure 1] Bone density scans were conducted in 0.029% of women and 0.009% of men, with a risk ratio of 3.102 (95% CI: 1.521, 6.326; P value 0.0010). The low number of bone density scans is explained by the fact that some of the healthcare organizations participating with TriNetX don’t report diagnostic tests. Regarding treatment, 13.998% of women and 8.222% of men received osteoporosis treatment, with a risk difference of 5.776% (P < 0.0001), a risk ratio of 1.702 (95% CI 1.659, 1.747), and the odds ratio was 1.817, favoring women.[Figure 2]Conclusion:This study highlights a significant gender disparity in the diagnosis and treatment of osteoporosis in patients with vertebral fractures. Women were more likely than men to be diagnosed with and treated for osteoporosis. These findings suggest a potential underdiagnosis and undertreatment of osteoporosis in men with vertebral fractures, underscoring the need for more vigilant screening and management strategies in this demographic.Figure 1.women vs men diagnosed with osteoporosis within 3 years after vertebral fracture diagnosis.Figure 2.women vs men received osteoporosis treatment within 3 years after vertebral fracture diagnosis.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Psoriatic arthritis (PsA) affects 4-30 percent of patients with psoriasis. PsA can affect peripheral joints, axial joints, and entheses. PsA has been linked to an increased risk of several comorbidities, including major cardiovascular events, particularly in cases not receiving treatment. Various treatments are available with different safety profiles.Objectives:In this observational, retrospective cohort study, we explore various outcomes in patients with PsA treated with Janus Kinase (JAK) inhibitors versus Interleukin 17 (IL-17) inhibitors. We utilized the TrinetX database, which includes electronic healthrecords from > 80 different global healthcare organizations.Methods:We studied patients aged 18 years and above diagnosed with psoriatic arthritis using International Classification of Diseases, Tenth Revision (ICD-10) codes. Two cohorts were created: cohort 1 receiving treatment with JAK inhibitors (tofacitinib or upadacitinib) (confirmed via RxNorm codes) and cohort 2 treated with IL 17 inhibitors (secukinumab, ixekizumab, or brodalumab). The analysis excluded individuals undergoing other alternative conventional or biological disease-modifying agents. The index event was defined as the initial appearance of PsA diagnosis and corresponding medications (JAK inhibitors vs interleukin 17 inhibitors) in patient records.We employed propensity score matching for age at the time of the index event, sex, race/ethnicity, and various comorbidities (diabetes mellitus, hyperlipidemia, hypertension, tobacco use, various neoplastic, endocrine diseases, and obesity). Our outcomes of interest included mortality, the incidence of acute myocardial infarction, cerebral infarction, heart failure, depression, suicidal ideations, suicidal attempts, lymphoma, pulmonary embolism, venous thrombosis, and arterial thrombosis or embolism occurring at any time following treatment initiation. Patients experiencing these outcomes before the index event were excluded. Measures of association were used to calculate risks and risk ratios.Results:Our analysis included 454 patients receiving JAK inhibitors (cohort 1) and 3,316 PsA patients receiving IL-17 inhibitors (cohort 2). Before propensity score matching, a slight age difference was noted between the two cohorts. Both cohorts primarily consisted of white patients, with a gender distribution leaning more towards females. Before matching, only slight differences were found in the rates of the selected comorbidities.After propensity score matching, 453 patients were included from both groups, and outcomes were calculated. The analysis revealed a higher risk observed in the PsA group on JAK inhibitor treatment for arterial embolism and thrombosis, with a risk difference of 2.212% (95% CI 0.85-3.57; P 0.0015). Additionally, a higher risk was observed in the same group for acute myocardial infarction, with a risk difference of 2.232% (95% CI 0.86-3.6; P 0.0016). Moreover, a higher risk was observed in the cohort of PsA patients receiving JAK inhibitors for cerebral infarction, with a risk difference of 2.262% (95% CI 0.87-3.64; P 0.0014).There was a greater risk of depression in the JAK inhibitor group, with a risk difference of 7.27% (95% CI 3.76-10.77; P < 0.0001) and a risk ratio of 3.69. More instances of lymphoma were observed in the JAK inhibitor cohort, with a risk difference of 2.222% (95% CI 0.86-3.58; P 0.0014). There was no statistically significant risk difference in mortality, pulmonary embolism, deep venous thrombosis, suicidal ideation, and heart failure. Moreover, there were no instances of suicidal attempts or pulmonary tuberculosis in either cohort.Conclusion:Our research suggests that PsA patients receiving JAK inhibitors may face increased risks of arterial embolism or thrombosis, acute myocardial infarction, cerebral infarction, depression, and lymphoma compared to those on IL-17 inhibitors. To confirm the observed risks and explore potential contributing factors, additional research with larger sample sizes and longer-term follow-ups is essential. We emphasize the importance of continuous monitoring of patient outcomes and safety profiles.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Case PresentationEarly diagnosis and rapid treatment of cancer is essential for good clinical outcomes for patients. In this case, an 85-year-old man presented with failure to thrive and was noted to have rapid-onset, multiple seborrheic keratoses (Leser-Trélat sign) on his chest and back. He was ultimately diagnosed with pancreatic cancer using computed tomography.DiscussionLeser-Trélat sign is a rare cutaneous marker for underlying malignancy. Identification of this sign can help guide diagnostic imaging and lab work to identify an occult internal malignancy, resulting in more rapid diagnosis, earlier treatment, and potentially better clinical outcomes.

Since the Patient Safety Authority introduced the I AM Patient Safety awards in 2013, this annual contest has celebrated hundreds of teams and individuals for their advancements, outcomes, and commitment to patient safety. The awards are judged by a cross-section of national and regional healthcare executives; patient safety advocates; and government, university, and patient representatives. These judges evaluated nominations from healthcare facilities throughout Pennsylvania and nationwide for innovation, impact, sustainability, and scalability. In addition to the honorees in 10 juried categories, PSA Executive Director Regina Hoffman, MBA, RN, selected a Choice Award winner for special recognition.