Repeated immunization with ATRA-containing liposomal adjuvant transdifferentiates Th17 cells to a Tr1-like phenotype.

In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell. Whilst ATRA was previously found to broadly reduce Th17 responses, we found that antigen formulated in ATRA-containing cationic liposomes only inhibited Th17 cells in an antigen-specific manner and not when combined with an irrelevant antigen. Furthermore, this approach shifted existing Th17 cells away from IL-17A expression and transcriptomic analysis of sorted Th17 lineage cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, vaccination with myelin-specific (MOG) antigen in ATRA-containing liposomes reduced Th17 responses and alleviated disease. This highlights the potential of therapeutic vaccination for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.

N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic. N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis. METHODS: Mice were challenged intratracheally or intravenously with LPS, or intratracheally with S. aureus to induce pneumonia and sepsis, and then were treated intravenously with OLDA. Endpoints included plasma cytokines, leukocyte activation marker expression, mouse sepsis scores, lung histopathology, and bacterial counts. The role of TRPV1 in the effects of OLDA was determined using Trpv1-/- mice, and mice with TRPV1 knockdown pan-neuronally, in peripheral nervous system neurons, or in myeloid cells. Circulating monocytes/macrophages were depleted using clodronate to determine their role in the anti-inflammatory effects of OLDA in endotoxemic mice. Levels of exogenous OLDA, and of endovanilloids and endocannabinoids, at baseline and in endotoxemic mice, were determined by LC-MS/MS. RESULTS: OLDA administration caused an early anti-inflammatory response in endotoxemic and septic mice with high serum levels of IL-10 and decreased levels of pro-inflammatory cytokines. OLDA also reduced lung injury and improved mouse sepsis scores. Blood and lung bacterial counts were comparable between OLDA- and carrier-treated mice with S. aureus pneumonia. OLDA's effects were reversed in mice with pan-neuronal TRPV1 knockdown, but not with TRPV1 knockdown in peripheral nervous system neurons or myeloid cells. Depletion of monocytes/macrophages reversed the IL-10 upregulation by OLDA in endotoxemic mice. Brain and blood levels of endovanilloids and endocannabinoids were increased in endotoxemic mice. CONCLUSIONS: OLDA has strong anti-inflammatory actions in mice with endotoxemia or S. aureus pneumonia. Prior studies focused on the role of peripheral nervous system TRPV1 in modulating inflammation and pneumonia. Our results suggest that TRPV1-expressing central nervous system neurons also regulate inflammatory responses to endotoxemia and infection. Our study reveals a neuro-immune reflex that during acute inflammation is engaged proximally by OLDA acting on neuronal TRPV1, and through a multicellular network that requires circulating monocytes/macrophages, leads to the systemic production of IL-10.

Association of ictal imaging changes in status epilepticus and neurological deterioration.

OBJECTIVE: In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge. METHODS: The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes. RESULTS: Of 261 eligible patients, 101 received at least one MRI during SE or within 7 days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n = 20) and without (n = 81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24 h and hardly seen >5 days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies. SIGNIFICANCE: In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.

Catecholaminergic Vasopressors Reduce Toll-Like Receptor Agonist-Induced Microvascular Endothelial Cell Permeability But Not Cytokine Production.

OBJECTIVES: Catecholaminergic vasopressors are the cornerstone of circulatory shock management. Nevertheless, catecholamines have problematic side effects, arousing a growing interest in noncatecholaminergic agents such as vasopressin or angiotensin-II. However, their respective effects on sepsis-associated microvascular endothelial dysfunction such as permeability or inflammation remain elusive. We investigated the role of catecholamines and other vasopressors on Toll-like receptor agonists-induced microvascular endothelial permeability and inflammation. SETTING: University research laboratory/cell research. SUBJECTS: Human pulmonary microvascular endothelial cells from multiple donors. INTERVENTION: Confluent monolayers of human pulmonary microvascular endothelial cells were treated with Toll-like receptor agonists (lipopolysaccharide, Poly[I:C], or tripalmitoyl-S-glyceryl cysteine) in the presence or absence of epinephrine, norepinephrine, vasopressin, and angiotensin-II. Permeability was inferred from transendothelial resistance, measured using electrical cell impedance sensing, where decreased transendothelial resistance is consistent with increased permeability. Cell-cell junction molecule expression was assessed via immunofluorescence microscopy and flow cytometry. We quantified cytokines in supernatants of Toll-like receptor agonist-treated human pulmonary microvascular endothelial cells. MEASUREMENTS AND MAIN RESULTS: Epinephrine and norepinephrine both ameliorate lipopolysaccharide, polyinosinic:polycytidylic acid, or tripalmitoyl-S-glyceryl cysteine-induced reductions in transendothelial resistance, a surrogate for endothelial permeability. In contrast, the noncatecholaminergic agents, vasopressin, and angiotensin-II did not affect Toll-like receptor agonists-induced reductions in transendothelial resistance. ß1- and ß2-adrenergic receptor antagonists reduced the effects of the catecholamines on transendothelial resistance, whereas α-adrenergic receptor antagonists did not. We observed that epinephrine and norepinephrine induced actin cytoskeletal rearrangement and normalized the membrane expression of proteins involved with adherens-junctions (vascular endothelial-cadherin) and tight-junctions (zona occludens-1). Despite having a substantial effect on endothelial permeability, epinephrine and norepinephrine did not affect human pulmonary microvascular endothelial cell survival or production of interleukin-8, interleukin-6, or monocyte chemoattractant protein-1 (CCL-2) induced by Toll-like receptor agonists, suggesting that these functions are regulated separately from permeability. CONCLUSIONS: Our findings demonstrate that treatment with epinephrine or norepinephrine strongly reduces endothelial permeability induced by agonists of multiple Toll-like receptors (Toll-like receptor-2, Toll-like receptor-3, Toll-like receptor-4) in vitro. Our studies suggest that both ß1- and ß2-adrenergic receptors mediate the stabilizing effects of epinephrine and norepinephrine on the endothelial barrier.

Bridging the GAP: Leveraging Partnerships to Bring Quality Nutrition Education to the Gardening Apprenticeship Program.

In the United States, about 12% of households are food-insecure, which can have negative health outcomes for children, including delayed development and early onset of obesity. Although many programs prioritize children, few evidence-based interventions exist for adolescents that address nutrition education. One promising intervention is teaching adolescents how to cook healthy meals. The Los Angeles Trust for Children's Health partnered with The Los Angeles Neighborhood Land Trust to integrate nutrition education and hands-on cooking demonstrations into an after-school program called the Gardening Apprenticeship Program at a local high school. Designed as a yearlong intervention, the Gardening Apprenticeship Program involves garden-based activities teaching food and environmental justice. Cultivating partnerships with other community-based organizations can help build capacity to pilot and replicate similar programs in other communities in food deserts.

Severe hypersomnia after unilateral infarction in the pulvinar nucleus- a case report.

BACKGROUND: Although a central role of the thalamus for sleep regulation is undisputed, the exact localization of the crucial structures within the thalamus remains controversial. CASE PRESENTATION: Here we report a 35 year old woman with no prior comorbidities who developed severe and persistent hypersomnia with long sleep time after a small right-sided MRI-verified thalamic stroke affecting the dorsal part of the pulvinar and the dorsolateral boarders of the dorsomedial nuclei. CONCLUSION: The observed symptoms suggest a crucial role of posterior thalamus but not the midline parts of the thalamus in sleep-wake control.

The compensatory enlargement of the remaining thyroid lobe following hemithyroidectomy is small and without impact on symptom relief.

According to previous studies, hemithyroidectomy results in growth of the remaining thyroid lobe by up to 30% in first 12 months after surgery. However, this estimate is based on imprecise methods, high inter- and intra-observer variability, and lack of blinding of the measurements. Furthermore, it is unknown whether enlargement of the remaining hemi-thyroid interferes with the improvement in symptoms after surgery for goiter. We aimed to assess the impact of postoperative thyroid growth on goiter symptom relief following hemithyroidectomy in patients with benign nodular goiter. Outcomes were measured before and 6 months after hemithyroidectomy in 44 patients. Thyroid volumes were determined by two independent and blinded observers using magnetic resonance imaging (MRI). Inter- and intra-observer variability was visualized by Bland-Altman plots. Goiter symptoms were assessed by the Thyroid-Specific Patient-Reported-Outcome Questionnaire (ThyPRO) on a scale from 0 to 100 points. After hemithyroidectomy, the remaining thyroid lobe was 13.7 ± 6.4 mL, and enlarged by a mean of 1.8 mL over 6 months [95% confidence interval (CI) (1.6; 2.1), p < 0.001], corresponding to an increase of 17% [95% CI (12; 22)]. The Goiter Symptom score improved by 27 points [95% CI (21; 34), p < 0.0001] from median 39 points (range 2-86) at baseline, and was unaffected by the compensatory thyroid growth. Six months after hemithyroidectomy, using blinded MRI evaluations, we demonstrated a small but significant postoperative growth of the remaining hemi-thyroid, which did not significantly affect the considerable improvement in goiter symptoms.

Trends in tumors in the central nervous system in elderly in Denmark, 2008-2012.

BACKGROUND: Tumors in the central nervous system (CNS) comprise a heterogeneous group of tumors with different treatment strategies and prognoses. Current treatment regimens are based on studies on patients mainly younger than 70 years. The aim of the present study was to analyze and describe trends in incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on patients older than 70 years. MATERIAL AND METHODS: Tumors in the CNS were defined as ICD-10 codes C70-72, D32-33 and D42-43. Data with comparable data on cancer incidence, mortality, prevalence and relative survival derived from the NORDCAN database were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. RESULTS: During the period 1980-2012 the number of patients with CNS tumors increased from 603 to 1378 patients. The increase is seen mainly in the elderly patients, and especially in women aged 84-89 and 90 + at the time of diagnosis. During the same time period, the mortality rates increased within all age groups, most significantly in patients aged 70 years or older. This may reflect an increased focus on and identification of these patients. Noteworthy; the number of patients living with a CNS tumor increased from 2952 in 1980 to 12 147 patients in 2010. CONCLUSION: This study suggests that the current treatment strategies in general may have improved survival in patients with CNS tumors, but in order to improve survival further in the increasing group of elderly patients more knowledge about treatment of these patients is needed.

Factors that influence Asian American college students use of mental health services: A systematic mixed studies review.

WHAT IS KNOWN ON THE SUBJECT?: Only 8.6% Asian Americans (AAs) report seeking mental health services compared to nearly 18% of the general population. There is a stigma against seeking mental health services among AAs. Mental illness is thought to be caused by a lack of harmony of emotions or evil spirits leading to delay in treatment among AAs. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Asian students are hesitant to use mental health services because they are balancing their desire to be part of the two cultures. Concepts used to define culture were found to have overlapping aspects of how researchers operationally define them, and few studies examined a combination of these concepts as a means of examining interactions between the concepts. AA emerging adults feel pressure through personal stigma from elders to 'save face' by keeping their problems to themselves or within the family to maintain a positive reputation for the family. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The overlap of conceptual definitions to understand cultural beliefs and values affecting measurement have complicated the interpretation of the research. Future research should include a multidimensional operationalization of culture that includes acculturation, ethnic identity, personal stigma and their effect on mental health help-seeking attitudes. Differences between South Asian and East Asian philosophical and cultural perspectives could influence access to mental health services; therefore, future studies should consider sampling that would allow for comparison of the groups. Understanding the factors that influence mental health help-seeking behaviours can determine intervention strategies to improve AA emerging adult mental health. ABSTRACT: INTRODUCTION: Only 8.6% of Asian Americans (AA) sought mental health services compared to 18% of United States population. AA college students report higher levels of mental health concerns compared to White students. AIM: The purpose of this systematic review was to identify the factors that influence AA students' mental health help-seeking behaviours. METHOD: Employing a data-based convergent synthesis design. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of the sample. Inclusion criteria were peer-reviewed studies published in English, focused on AA college students' mental health seeking attitudes in United States. RESULTS: The final sample was forty-four studies. Four themes emerged: acculturation, ethnic identity, racism and stigma. There were discrepant findings regarding how acculturation affects mental health help-seeking attitudes. Several studies included more than one theme in their analyses. The different concepts included across studies make it difficult to compare the findings. DISCUSSION: There is some overlap between acculturation and ethnic identity that could affect the analysis in studies where both concepts are included. Personal stigma negatively influences mental health help-seeking attitudes. IMPLICATIONS FOR PRACTICE: Defining culture to include acculturation, ethnic identity, personal stigma can help in understanding their effect on mental health help-seeking attitudes.

Common misperceptions and public knowledge about intrauterine devices among US-based online respondents.

OBJECTIVES: Misperceptions about intrauterine devices (IUDs) may dissuade potential users and public beliefs are not well understood. We sought to describe public knowledge of mechanism of action, failure rate, and IUD health risks. Secondary objectives included identifying inaccurate information and information sources about IUDs. STUDY DESIGN: We conducted a convenience-based survey of participants living in the United States 18 years and older using Amazon Mechanical Turk and ResearchMatch. We collected information on demographics, reproductive history, and IUD knowledge. We asked about IUD mechanism of action, failure rate, potential health risks, and information sources. We used multivariable logistic regression to test the association between gender and perceived lower (vs. higher) risks of IUDs. RESULTS: We included 1597 individuals with 726 (45.5%) self-reported men and 871 (54.5%) self-reported women. For both hormonal and non-hormonal IUDs, participants most often selected implantation prevention as the primary mechanism of action. In our sample, 55.5% of individuals believed the failure rate was greater than five percent. Weight gain, uterine perforation, and expulsion were cited as health risks likely to occur ≥5% of the time by 42.1%, 34.3%, and 38.4% of participants, respectively. Participants identified healthcare providers as their primary source of contraceptive information. Our multivariable logistic regression analysis revealed women had higher odds of perceiving IUDs as higher risk (aOR=1.35, 95% CI 1.09-1.68) compared to men. CONCLUSIONS: Individuals underestimated IUD effectiveness while overestimating perceived health risks. Our results highlight areas to target education about IUDs to support informed contraceptive decision-making. IMPLICATIONS: Participants misunderstood IUD mechanism of action, underestimated efficacy, and overestimated failure rates and health risks. Providers should begin clinical counseling by assessing baseline knowledge, since mechanism of action, side effect profiles, and concepts like female anatomy should not be assumed to be known.

Financial assistance and payment plans for underinsured patients shopping for "shoppable" hospital services.

Recent price transparency laws are designed to better inform patients as they compare hospital options and "shop" for health care services. In addition to prices, underinsured patients seeking care need information on financial assistance, discounts, payment plans, and upfront payment requirements to compare the affordability of care across hospitals. Little is known about the availability of this information and the experience of prospective patients seeking it. We contacted a random sample of 10% of general short-term hospitals across the United States in this "secret shopper" telephone study to assess financial options and navigation challenges faced by underinsured patients in need of a non-emergency procedure. The administrative friction was substantial. Most hospitals have 3 siloed offices for (1) financial assistance, (2) payment plans and discounts, and (3) upfront payment requirements. All relevant offices were unreachable in 3 attempted calls at 18.1% of hospitals. Among hospitals with available information, the majority have financial options for patients: 86.7% of hospitals offer financial assistance and 97.0% of hospitals offer payment plans to underinsured patients for non-emergency care. The length and terms of payments plans varied widely for hospital-administered and third-party financing arrangements. Upfront payments were sometimes required, potentially posing barriers for patients without cash or credit access.

Treatment of Meningiomas Involving the Optic Canal with Endoscopic Transnasal Decompression of the Optic Nerve.

BACKGROUND: Management of patients with optic nerve sheath meningiomas (ONSMs) is controversial and the treatment strategy in this patient group is still up for discussion. Transnasal endoscopic orbital and optic nerve decompression aims to reduce the pressure in the orbit and on the optic nerve and thereby prevent vision loss. This article presents material from 7 cases of transnasal endoscopic orbital decompression. METHODS: The study design is a retrospective cohort study. The aim was to include all patients with a meningioma residing along the nerve sheath and who were operated using endoscopic transnasal decompression of the orbit and if needed the optic canal at Odense University Hospital. Data from the medical records were collected and pre- and postoperative eye examinations were compared. In addition, it was recorded whether there were complications to the procedure and whether additional treatments were given. RESULTS: In total, 4 women and 3 men were included in the study. Four out of 7 patients experienced improvement in vision after the operation. One patient experienced unchanged vision and 2 patients experienced deterioration of vision after surgery. CONCLUSIONS: The current report of 7 patients with ONSM shows promising results for this surgical procedure as 4 out of 7 patients experienced improvement in their vision at follow-up examinations. The 2 patients who experienced deterioration of vision already had severely reduced vision preoperatively, which indicates that surgery should be considered before the vision becomes significantly reduced.

PDP type brain tumor in association with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by inactivating pathogenic variants in the tumor suppressor gene menin 1 on chromosome 11q13 (Falchetti et al., 2009). The syndrome is characterized by neoplasia in two or more endocrine glands and has a high degree of penetrance. Pathogenic germline multiple neoplasia type 1 variants primarily result in neoplasia affecting the parathyroid glands, the pancreatic islet cells, and the anterior pituitary in combination. Primary hyperparathyroidism is the most common pathological manifestation of the syndrome, followed by pancreatic neuroendocrine tumors. Important genetic confirmation has been provided showing that ependymoma should be considered as a neoplasm that can occur in patients with MEN1 (Kato et al., 1996; Cuevas-Ocampo et al., 2017). The biphasic histopathological tumor entity shown in the present case we name Pleomorphic Xanthoastocytoma grade 3 differential pathology (PDP) in association with Multiple Endocrine Neoplasia type 1. This MEN1 associated tumor subtype is an extension of the findings on MEN1 associated ependymoma, where we show that the clinical phenotype itself may potentially be triggered by a frameshift germline pathogenic variant for the MEN1 gene, in combination with cyclin-dependent kinase inhibitor 1B gene germline variant and cyclin dependent kinase inhibitor 2A somatic deletion downstream of menin.

Facile iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethanes and exploration of applications.

A practical strategy for the iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethane and its derivatives has been developed. These compounds exhibit high cytotoxicity toward various cancer cell lines and moreover they are promising ligands for the Cu-catalysed synthesis of quinolines.

PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients.

The ErbB2-targeting antibody, trastuzumab (Herceptin), has remarkable therapeutic efficacy in certain patients with ErbB2-overexpressing tumors. The overall trastuzumab response rate, however, is limited and what determines trastuzumab response is poorly understood. Here we report that PTEN activation contributes to trastuzumab's antitumor activity. Trastuzumab treatment quickly increased PTEN membrane localization and phosphatase activity by reducing PTEN tyrosine phosphorylation via Src inhibition. Reducing PTEN in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Patients with PTEN-deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. Thus, PTEN deficiency is a powerful predictor for trastuzumab resistance. Additionally, PI3K inhibitors rescued PTEN loss-induced trastuzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance.

The treatment of acute lymphoblastic leukemia in Jehovah's Witnesses and patients who cannot accept blood products.

Jehovah's Witnesses cannot accept blood products based upon religious beliefs, and when they present with acute leukemia, the ideal treatment strategy can be controversial. We present six cases of Jehovah's Witnesses with acute lymphoblastic leukemia and show that complete remission can be achieved without using anthracycline in 83% (5/6) of patients. We also report, for the first time in this population, that the use of agents with novel mechanisms of action, such as blinatumomab and nelarabine, is associated with minimal myelosuppression and can produce durable responses, with 2 of 6 patients still alive in CR3 at 4.9 and 6.6 years.

[Amphetamine-induced toxic encephalopathy].

In this case report, a 40-year-old woman presented with altered mentation, central facial palsy and hemiparesis. Acute CT scan showed several hypodense, rounded areas in both hemispheres. Urine toxicology tested positive for amphetamine. Subsequent cerebral MRI had hyperintense T2-weighted fluid-attenuated inverse recovery (FLAIR) lesions in both hemispheres, indicating demyelinating disease. A biopsy was made from one of the lesions. The final diagnosis was toxic encephalopathy.

Phenotypic manifestations in FLNA-related periventricular nodular heterotopia: a case report and review of the literature.

Periventricular nodular heterotopia (PVNH) is an X-linked disease caused by loss-of-function variants in the filamin A (FLNA) gene. FLNA-PVNH is a heterogeneous disorder, and the phenotype is associated with neurological and non-neurological features including cardiovascular, gastrointestinal, pulmonary, haematological, cutaneous and skeletal manifestations. No clear definition of the FLNA-PVNH phenotype has been established, but the patients are predominantly females with seizures, cardiovascular manifestations, and normal intelligence or mild intellectual disability. Herein, we describe a PVNH patient diagnosed with a novel heterozygous missense variant in FLNA after an atypical presentation of deep vein thrombosis and thrombocytopenia. Clinical evaluation found hypermobility, cardiovascular and skin manifestations. Moreover, we conducted a literature review of 186 FLNA-PVNH patients to describe the phenotypic spectrum. In conclusion, our patient highlights the importance of thorough clinical evaluation to identify manifestations in this very heterogeneous disorder. The phenotypic review may guide clinicians in the assessment and follow-up of FLNA-PVNH patients.

Rheumatic disease patient decision-making about COVID-19 vaccination: a qualitative analysis.

BACKGROUND: Although patients with rheumatic and musculoskeletal diseases (RMDs) are at increased risk for adverse outcomes of COVID-19 illness compared to healthy controls, they also have lower rates of willingness to be vaccinated. Previous research has identified reasons for vaccine hesitancy among patients with RMDs (such as concerns about side effects and flares), but little is known about what these reasons mean in the context of patients' lives, or how vaccine decision making is experienced from a patient perspective. Our objective was to describe decision-making about COVID-19 vaccination among RMD patients. METHODS: Participants in a RMD registry were invited to complete monthly online surveys regarding COVID-19 vaccination from March-June 2021. We qualitatively analyzed comments from two open-ended survey questions reporting general experiences with vaccination and side effects. Comments were coded for attitudes towards COVID-19 vaccination, vaccine access, rheumatologic medication management around vaccination, and vaccine side effects. Themes were identified for the process and context of COVID-19 vaccine decisions, patient motivations for receiving or avoiding vaccination, and consistency of peri-vaccine medication management with current ACR guidelines. RESULTS: We analyzed 710 comments from 537 respondents. Commenting respondents had a mean age of 64 years, were 87% female, 94% white, and 93% received/intended to receive ≥ 1 dose of a COVID-19 vaccine. Desire for protection and a return to normal routines motivated some commenters to get vaccinated, while concerns about vaccine side effects motivated others to delay or avoid vaccination. Several commenters reported disease flares following vaccination. Some commenters did not consult their providers about vaccination and failed to withhold immunomodulatory medications during vaccination, while others withheld medications more conservatively than recommended by current ACR guidelines, either on their own or directed by their provider. CONCLUSIONS: While most commenters were vaccine-accepting, challenges to COVID-19 vaccine uptake in the RMD population may include fears of side effects, including worsened RMD symptoms, and perceptions that vaccination is unnecessary. Addressing these concerns and beliefs may be critical for promoting vaccination in this population.