Enhanced Type 1 Interferon Signature in Axial Spondyloarthritis Patients Unresponsive to Secukinumab Treatment.

OBJECTIVE: Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive IL-17A-producing cells are implicated in a central role. Therapeutically, biologics that target IL-17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some axSpA patients do not respond to IL-17A blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR). METHODS: Peripheral blood mononuclear cells were collected from 30 axSpA patients before and 24-weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC-R and SEC-NR using flow cytometry. Mature CD45RO+CD45RA-CD4+ T cells were FACS sorted, and RNA was measured using NanoString analysis. RESULTS: SEC-NR had an increased frequency of IL-17A-producing RORγt+CD4+ T cells compared to HCs at pre-secukinumab (p<0.01). SEC-NR had a significant increase of CXCR3+ CD4+ T cells pre-secukinumab compared to SEC-R (p<0.01). Differentially expressed gene analysis revealed upregulation of type 1 interferon-regulated genes in SEC-NR patients compared to SEC-R post-biologic. SEC-R patients had an upregulated cytotoxic CD4+ T cell gene signature pre-secukinumab compared to SEC-NR patients. CONCLUSIONS: The increased frequency of IL-17A-producing cells in SEC-NR patients suggests a larger inflammatory burden than SEC-R patients. With treatment, SEC-NR patients have a more pronounced type 1 IFN signature than SEC-R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.

Non-contrast MRI Surveillance of Craniopharyngiomas using a balanced steady state free precession (bSSFP) sequence.

BACKGROUND AND PURPOSE: Contrast-enhanced MRI (CEMRI) is a commonly used imaging modality for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non-contrast enhanced MRI (NCMRI) with a balanced steady state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. MATERIALS AND METHODS: 29 craniopharyngioma patients (16 female/13 male, mean age=21.5± 4.3 years) with CEMRIs including a bSSFP sequence were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on noncontrast and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated using paired t-tests. Diagnostic confidence levels for NC-and CE evaluations were measured using a 3-point scale (2=confident,1=adequate,0=unsure). Analyses of tumor involvement of cranial nerves and adjacent vasculature and diagnostic confidence were performed using Fisher's exact and chi-square tests. RESULTS: No significant difference was observed between residual tumor volumes in both studies (18.86±21.67 cm3 vs 17.64±23.85 cm3, p=0.55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71±3.47 cm3 vs 3.95±5.51 cm3, p=0.10; 2.5±1.5 vs 2.9±1.5, p=0.10; 7.61±13.41 vs 6.84±13.37 cm3, p=0.22, respectively). Tumoral involvement of cranial nerves II (p=0.64), III (p=0.42), and adjacent vasculature (p=0.05) showed no significant differences in detection. Diagnostic confidence was comparable evaluating cranial nerve II, vascular structures, and third ventricle (p>0.05) involvement. Higher levels of confidence were observed with bSSFP sequences for detection of cranial nerve III involvement (p=0.0001) and with ce-T1W for cavernous sinus involvement (p=0.02). CONCLUSIONS: NCMRI techniques using a bSSFP sequence provides similar characterization of craniopharyngiomas as contrast enhanced techniques. ABBREVIATIONS: 3D DRIVE, 3-dimensional driven equilibrium; ACA, anterior cerebral artery; bSSFP, balanced steady-state free precession; ce-T1W, contrast-enhanced T1-weighted imaging; CN, cranial nerve; GTR, gross total resection; STR, subtotal resection.

Severe cerebral amyloid angiopathy related inflammation (CAA-ri) associated with vaccination: Case report and literature review.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rapid but reversible autoimmune encephalopathy where spontaneous autoantibody reaction against amyloid beta deposited in cerebral blood vessels produces characteristic neuroinflammatory changes such as vasogenic edema and microhemorrhages on MRI. The term amyloid-related imaging abnormalities (ARIA) is sometimes used to describe these changes but are more often reserved for similar MRI signal abnormalities seen after administration of anti-amyloid immunotherapy, using treatment exposure as an antecedent. It is unclear if there is any biological basis for this dichotomized distinction. We report a case of severe CAA-ri after exposure to SARS-CoV-2 vaccine and performed a literature review of CAA-ri related to vaccination. CAA-ri precipitated by immunogenic triggers other than anti-amyloid therapy would lend support to the hypothesis that ARIA seen on MRI may represent the same disease underpinned by a shared anti-Aß autoantibody response irrespective of etiology. A thorough history should be taken before labelling CAA-ri as spontaneous.

Training the Next Generation of the Human Immunodeficiency Virus Workforce: Needs, Challenges, and Opportunities.

Due to remarkable advancements in medications, more people are living longer with human immunodeficiency virus (HIV). The HIV workforce has been strained by a supply-demand mismatch, threatening the care of an aging population with multiple comorbidities. Solving the HIV workforce shortage requires multiple novel and creative solutions that recruit new trainees to the field, increase the workforce diversity, and improve disparities in access to care. New and expanded models of care that incorporate a wider array of clinicians and optimize the use of team-based care will also be crucial.

An Unusual Case of Pheochromocytoma Associated with von Hippel-Lindau Disease and Lynch Syndrome During Pregnancy.

Pheochromocytomas (PCCs) and/or paragangliomas (PGLs) are a challenge to diagnose during pregnancy because of elusive signs and testing difficulties. We report a 25-year-old woman with no pertinent medical history who presented to the hospital with hypertension, vision loss, and weakness and was initially diagnosed with preeclampsia. Imaging showed hemangioblastomas in the medulla and thoracic spine, pancreatic cysts, and a renal cyst. The endocrinology service was consulted for possible PCCs associated with von Hippel-Lindau disease (VHL). Serum and urine normetanephrine levels were elevated despite the lack of overt PCCs/PGLs seen on magnetic resonance imaging and magnetic resonance angiography. The patient was medically managed with doxazosin and then labetalol. Despite successful resection of the hemangioblastoma in the medulla, the patient suffered respiratory distress requiring tracheostomy and venous-venous extracorporeal membrane oxygenation (V-V ECMO) and fetal demise. After 3 months, the patient was discharged to rehabilitation. Follow-up genetics were heterozygous for VHL and Lynch syndrome. DOTATATE positron emission tomography/computed tomography scan showed a small hepatic focus of a maximum standard uptake value of 12.1. Altogether, this case illustrates the importance of prompt diagnosis and proper management of PCCs/PGLs during pregnancy and incorporating genetic information during surveillance to lower morbidity and mortality.

Direct to Patient Synchronous Teledermatology During COVID-19 Pandemic.

Background: During the COVID-19 pandemic, teledermatology became a popular mode of health care delivery. Thus, deciphering which diagnoses are best suited for synchronous video visits is important to guide providers on appropriate patient care. Methods: We conducted a retrospective study of 1,647 submitted synchronous video visits from September 1, 2020 to March 31, 2021 at a single, large academic institution. Results: Video visits' follow-up rate was significantly associated with diagnosis subtype (p < 0.001). Compared with patients with skin lesions and nonskin dermatologic conditions, patients with a rash had higher odds of being recommended to have their follow-up visit as a video visit (odds ratio [OR] = 0.222, p < 0.001; OR = 0.296, p < 0.001). Patients with a rash had lower odds of being recommended to have their follow-up visit as an in-person office visit when compared with skin lesions (OR = 9.679, p < 0.001), nonskin dermatologic conditions (OR = 4.055, p < 0.001), and other skin dermatologic conditions (OR = 2.23, p < 0.01). Demographically, employed, middle-aged patients with private insurance made up the majority of video visit usage. African American patients were less likely to utilize a video visit compared with Asian patients (OR = 2.06, p < 0.038). Conclusions: Certain dermatologic diagnoses, most notably rashes, are more conducive to video visit management. Rashes made up 86% of new patient video visits, were more likely to have video visit follow-up if needed and were more likely to not require further follow-up indicating that the management of rashes from initial diagnosis to completion in care is suitable for video visit management.

GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV.

BACKGROUND: Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. METHODS: A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. RESULTS: A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss. CONCLUSIONS: Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.

The Administrative Burden on Palliative Academic Physicians.

CONTEXT: Burnout is frequently a workload-related syndrome among palliative care physicians. Mandatory administrative activities contribute to this workload. The purpose of this study was to measure the amount of time involved in multiple required administrative activities and the cost of this on academic healthcare facilities. METHODS: We measured all mandatory and non-mandatory activities that need to be completed by faculty and reviewed them with all Department of Palliative, Rehabilitation, and Integrative Medicine members for accuracy. RESULTS: Every faculty member spends annually an approximate average of 5300 minutes on administrative activities (approximately the equivalent of 29 consults plus 133 follow-ups). Using the department net average per encounter, the approximate value of these encounters is $36,936 for each faculty member (about 11 clinical days). CONCLUSION: Academic palliative care physicians are required to complete a number of administrative activities. Institutions do not keep a registry of these activities and do not accommodate for them with a reduction in the annual clinical productivity requirements. We recommend that regulatory agencies and institutions work together to better regulate this list of tasks and their frequency.

Chatbot Performance in Defining and Differentiating Palliative Care, Supportive Care, Hospice Care.

CONTEXT: Artificial intelligence (AI) chatbot platforms are increasingly used by patients as sources of information. However, there is limited data on the performance of these platforms, especially regarding palliative care terms. OBJECTIVES: We evaluated the accuracy, comprehensiveness, reliability, and readability of three AI platforms in defining and differentiating "palliative care," "supportive care," and "hospice care." METHODS: We asked ChatGPT, Microsoft Bing Chat, Google Bard to define and differentiate "palliative care," "supportive care," and "hospice care" and provide three references. Outputs were randomized and assessed by six blinded palliative care physicians using 0-10 scales (10 = best) for accuracy, comprehensiveness, and reliability. Readability was assessed using Flesch Kincaid Grade Level and Flesch Reading Ease scores. RESULTS: The mean (SD) accuracy scores for ChatGPT, Bard, and Bing Chat were 9.1 (1.3), 8.7 (1.5), and 8.2 (1.7), respectively; for comprehensiveness, the scores for the three platforms were 8.7 (1.5), 8.1 (1.9), and 5.6 (2.0), respectively; for reliability, the scores were 6.3 (2.5), 3.2 (3.1), and 7.1 (2.4), respectively. Despite generally high accuracy, we identified some major errors (e.g., Bard stated that supportive care had "the goal of prolonging life or even achieving a cure"). We found several major omissions, particularly with Bing Chat (e.g., no mention of interdisciplinary teams in palliative care or hospice care). References were often unreliable. Readability scores did not meet recommended levels for patient educational materials. CONCLUSION: We identified important concerns regarding the accuracy, comprehensiveness, reliability, and readability of outputs from AI platforms. Further research is needed to improve their performance.

Characterization of patients with brain metastases referred to palliative care.

PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.

A Journey of Diagnosing a Case of Immune Checkpoint Inhibitor Pembrolizumab-Induced Diabetes Mellitus.

Autoimmune diabetes mellitus (DM) due to pembrolizumab is a rare but reported complication of immune checkpoint inhibitors (ICIs). It is often missed for a long initial period, leading to unnecessary admissions and poor glucose management. We report a case of a 72-year-old woman with prior history of gastrointestinal stromal tumor (GIST) and current diagnosis of squamous cell carcinoma (SCC) of the lung, who upon presentation at the emergency department with symptoms of encephalopathy, was diagnosed as having sodium glucose cotransporter 2 inhibitor (SGLT-2i)-induced diabetic ketoacidosis (DKA). Upon further investigation, we learned that this patient had multiple hospitalizations for recurrent DKA over 2 years after being managed on metformin and SGLT-2i. Biochemical testing helped confirm pembrolizumab-induced autoimmune diabetes with significantly elevated glutamic acid decarboxylase-65 (GAD65) autoantibodies and an undetectable C-peptide level. The patient has had clinical improvement with insulin therapy without further DKA episodes. She continued to be managed by outpatient endocrinology with improved glucose control. Altogether, this case demonstrates the importance of keeping a high vigilance for possible new onset of autoimmune endocrine diseases, such as diabetes, in patients treated with ICIs, to enable earlier diagnosis and prompt initiation of correct therapy.

Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis.

AIMS: American College of Cardiology/American Heart Association 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults are less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults <50. METHODS AND RESULTS: PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. Six observational studies with a total of 45 919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events [pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5]. Compared with a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, P = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, P = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, P < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, P < 0.0001). CONCLUSION: In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC > 100 was associated with a higher likelihood of cardiovascular events and mortality.

This paper compiles prior studies into a meta-analysis to clarify the ability of coronary artery calcium (CAC) to predict cardiovascular risk and mortality risk in adults < 55 years. • A mildly elevated CAC (1­100) in adults < 55 likely has an increased cardiovascular risk but does not appear to have an increased mortality risk. • A moderately or highly elevated CAC (>100) in adults < 55 has a substantial increase in cardiovascular risk and mortality risk.