An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3+ regulatory T (TR) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated TR population with elevated proliferation, a transcriptional program associated with Stat5- and T cell receptor-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface major histocompatibility complex class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 co-stimulatory ligands from maturing cDCs to TR cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes, resulting in T cell anergy. Thus, IL-2 mutein-expanded TR cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.

Taldefgrobep Alfa and the Phase 3 RESILIENT Trial in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a rare, genetic neurodegenerative disorder caused by insufficient production of survival motor neuron (SMN) protein. Diminished SMN protein levels lead to motor neuron loss, causing muscle atrophy and weakness that impairs daily functioning and reduces quality of life. SMN upregulators offer clinical improvements and increased survival in SMA patients, although significant unmet needs remain. Myostatin, a TGF-ß superfamily signaling molecule that binds to the activin II receptor, negatively regulates muscle growth; myostatin inhibition is a promising therapeutic strategy for enhancing muscle. Combining myostatin inhibition with SMN upregulation, a comprehensive therapeutic strategy targeting the whole motor unit, offers promise in SMA. Taldefgrobep alfa is a novel, fully human recombinant protein that selectively binds to myostatin and competitively inhibits other ligands that signal through the activin II receptor. Given a robust scientific and clinical rationale and the favorable safety profile of taldefgrobep in patients with neuromuscular disease, the RESILIENT phase 3, randomized, placebo-controlled trial is investigating taldefgrobep as an adjunct to SMN upregulators in SMA (NCT05337553). This manuscript reviews the role of myostatin in muscle, explores the preclinical and clinical development of taldefgrobep and introduces the phase 3 RESILIENT trial of taldefgrobep in SMA.

Evaluating ChatGPT as a Patient Education Tool for COVID-19-Induced Olfactory Dysfunction.

Objective: While most patients with COVID-19-induced olfactory dysfunction (OD) recover spontaneously, those with persistent OD face significant physical and psychological sequelae. ChatGPT, an artificial intelligence chatbot, has grown as a tool for patient education. This study seeks to evaluate the quality of ChatGPT-generated responses for COVID-19 OD. Study Design: Quantitative observational study. Setting: Publicly available online website. Methods: ChatGPT (GPT-4) was queried 4 times with 30 identical questions. Prior to questioning, Chat-GPT was "prompted" to respond (1) to a patient, (2) to an eighth grader, (3) with references, and (4) no prompt. Answer accuracy was independently scored by 4 rhinologists using the Global Quality Score (GCS, range: 1-5). Proportions of responses at incremental score thresholds were compared using χ 2 analysis. Flesch-Kincaid grade level was calculated for each answer. Relationship between prompt type and grade level was assessed via analysis of variance. Results: Across all graded responses (n = 480), 364 responses (75.8%) were "at least good" (GCS ≥ 4). Proportions of responses that were "at least good" (P < .0001) or "excellent" (GCS = 5) (P < .0001) differed by prompt; "at least moderate" (GCS ≥ 3) responses did not (P = .687). Eighth-grade level (14.06 ± 2.3) and patient-friendly (14.33 ± 2.0) responses were significantly lower mean grade level than no prompting (P < .0001). Conclusion: ChatGPT provides appropriate answers to most questions on COVID-19 OD regardless of prompting. However, prompting influences response quality and grade level. ChatGPT responds at grade levels above accepted recommendations for presenting medical information to patients. Currently, ChatGPT offers significant potential for patient education as an adjunct to the conventional patient-physician relationship.

Artery Grafting for Arterial Anastomoses in Head and Neck Free Tissue Transfer Reconstruction.

BACKGROUND: Vessel grafting is an important technique in head and neck free tissue transfer (FTT) reconstruction when a tension-free anastomosis is not otherwise feasible. To our knowledge, there are limited data regarding interposition artery grafts for arterial anastomoses in head and neck reconstruction. Here, we present a multi-institutional cohort of arterial interposition grafts for FTT reconstruction for head and neck defects. METHODS: A retrospective review was conducted at four tertiary care institutions for patients who underwent FTT reconstruction for head and neck defects which utilized an interposition artery graft for the arterial anastomosis. Charts were reviewed for type and length of artery grafts harvested, surgical indication, indication for artery graft, types of flaps harvested, and various preoperative characteristics (including history of radiation or previous FTT reconstruction surgery). Postoperative complications within postoperative day 30 were measured and reported. RESULTS: Nine patients met inclusion criteria. The lateral circumflex femoral artery (either transverse or descending branches) (n = 3) and facial artery (n = 3) were the most commonly harvested arteries. The scalp (n = 5) was the most common primary defect site. Seven grafts were harvested initially and in a planned fashion, while two were harvested as salvage techniques (either for flap salvage or vein graft failure). In planned grafts, arteries were the preferred interposition grafting method due to either size match preferences (n = 4) or similarities in wall thickness (n = 3) between graft and recipient artery. There were no reported cases of unplanned readmission, postoperative hematoma, fistula formation, wound infection, or donor site morbidities. Two patients required unplanned return to the operating room for flap compromise, both of which ultimately resulted in flap failure secondary to clot formation at both arterial and venous anastomoses. CONCLUSIONS: When arterial pedicle length is insufficient, interposition artery grafting is both a feasible and viable technique to achieve tension-free arterial anastomoses for select cases of highly complex head and neck free tissue reconstruction.

T cells promote distinct transcriptional programs of cutaneous inflammatory disease in human skin structural cells.

T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cell activity precipitates tissue pathology that occurs alongside disease-associated alterations of structural cell subsets, but the mechanisms by which T cells promote these changes remain unclear. We show that subsets of circulating and skin-resident CD4+ T cells promote distinct transcriptional outcomes in human keratinocytes and dermal fibroblasts that correspond with divergent T cell cytokine production. Using these transcriptional signatures, we identify T cell-dependent outcomes associated with inflammatory skin disease, including a set of Th17 cell-induced genes in keratinocytes that are enriched in the skin during psoriasis and normalized by anti-IL-17 therapy, and a skin-resident T cell-induced gene module enriched in scleroderma-associated fibroblasts. Interrogating clinical data using T cell-derived structural cell gene networks enables investigation of the immune-dependent contribution to inflammatory disease and the heterogeneous patient response to biologic therapy.

Chatbots as Patient Education Resources for Aesthetic Facial Plastic Surgery: Evaluation of ChatGPT and Google Bard Responses.

Background: ChatGPT and Google Bard™ are popular artificial intelligence chatbots with utility for patients, including those undergoing aesthetic facial plastic surgery. Objective: To compare the accuracy and readability of chatbot-generated responses to patient education questions regarding aesthetic facial plastic surgery using a response accuracy scale and readability testing. Method: ChatGPT and Google Bard™ were asked 28 identical questions using four prompts: none, patient friendly, eighth-grade level, and references. Accuracy was assessed using Global Quality Scale (range: 1-5). Flesch-Kincaid grade level was calculated, and chatbot-provided references were analyzed for veracity. Results: Although 59.8% of responses were good quality (Global Quality Scale ≥4), ChatGPT generated more accurate responses than Google Bard™ on patient-friendly prompting (p < 0.001). Google Bard™ responses were of a significantly lower grade level than ChatGPT for all prompts (p < 0.05). Despite eighth-grade prompting, response grade level for both chatbots was high: ChatGPT (10.5 ± 1.8) and Google Bard™ (9.6 ± 1.3). Prompting for references yielded 108/108 of chatbot-generated references. Forty-one (38.0%) citations were legitimate. Twenty (18.5%) provided accurately reported information from the reference. Conclusion: Although ChatGPT produced more accurate responses and at a higher education level than Google Bard™, both chatbots provided responses above recommended grade levels for patients and failed to provide accurate references.

Evaluating ChatGPT Responses on Atrial Fibrillation for Patient Education.

Background ChatGPT is a language model that has gained widespread popularity for its fine-tuned conversational abilities. However, a known drawback to the artificial intelligence (AI) chatbot is its tendency to confidently present users with inaccurate information. We evaluated the quality of ChatGPT responses to questions pertaining to atrial fibrillation for patient education. Our analysis included the accuracy and estimated grade level of answers and whether references were provided for the answers. Methodology ChatGPT was prompted four times and 16 frequently asked questions on atrial fibrillation from the American Heart Association were asked. Prompts included Form 1 (no prompt), Form 2 (patient-friendly prompt), Form 3 (physician-level prompt), and Form 4 (prompting for statistics/references). Responses were scored as incorrect, partially correct, or correct with references (perfect). Flesch-Kincaid grade-level unique words and response lengths were recorded for answers. Proportions of the responses at differing scores were compared using the chi-square analysis. The relationship between form and grade level was assessed using the analysis of variance. Results Across all forms, scoring frequencies were one (1.6%) incorrect, five (7.8%) partially correct, 55 (85.9%) correct, and three (4.7%) perfect. Proportions of responses that were at least correct did not differ by form (p = 0.350), but perfect responses did (p = 0.001). Form 2 answers had a lower mean grade level (12.80 ± 3.38) than Forms 1 (14.23 ± 2.34), 3 (16.73 ± 2.65), and 4 (14.85 ± 2.76) (p < 0.05). Across all forms, references were provided in only three (4.7%) answers. Notably, when additionally prompted for sources or references, ChatGPT still only provided sources on three responses out of 16 (18.8%). Conclusions ChatGPT holds significant potential for enhancing patient education through accurate, adaptive responses. Its ability to alter response complexity based on user input, combined with high accuracy rates, supports its use as an informational resource in healthcare settings. Future advancements and continuous monitoring of AI capabilities will be crucial in maximizing the benefits while mitigating the risks associated with AI-driven patient education.

Evaluating ChatGPT-3.5 and ChatGPT-4.0 Responses on Hyperlipidemia for Patient Education.

Introduction Hyperlipidemia is prevalent worldwide and affects a significant number of US adults. It significantly contributes to ischemic heart disease and millions of deaths annually. With the increasing use of the internet for health information, tools like ChatGPT (OpenAI, San Francisco, CA, USA) have gained traction. ChatGPT version 4.0, launched in March 2023, offers enhanced features over its predecessor but requires a monthly fee. This study compares the accuracy, comprehensibility, and response length of the free and paid versions of ChatGPT for patient education on hyperlipidemia. Materials and methods ChatGPT versions 3.5 and 4.0 were prompted in three different ways and 25 questions from the Cleveland Clinic's frequently asked questions (FAQs) on hyperlipidemia. Prompts included no prompting (Form 1), patient-friendly prompting (Form 2), and physician-level prompting (Form 3). Responses were categorized as incorrect, partially correct, or correct. Additionally, the grade level and word count from each response were recorded for analysis. Results Overall, scoring frequencies for ChatGPT version 3.5 were: five (6.67%) incorrect, 18 partially correct (24%), and 52 (69.33%) correct. Scoring frequencies for ChatGPT version 4.0 were: one (1.33%) incorrect, 18 (24.00%) partially correct, and 56 (74.67%) correct. Correct answers did not significantly differ between ChatGPT version 3.5 and ChatGPT version 4.0 (p = 0.586). ChatGPT version 3.5 had a significantly higher grade reading level than version 4.0 (p = 0.0002). ChatGPT version 3.5 had a significantly higher word count than version 4.0 (p = 0.0073). Discussion There was no significant difference in accuracy between the free and paid versions of hyperlipidemia FAQs. Both versions provided accurate but sometimes partially complete responses. Version 4.0 offered more concise and readable information, aligning with the readability of most online medical resources despite exceeding the National Institutes of Health's (NIH's) recommended eighth-grade reading level. The paid version demonstrated superior adaptability in tailoring responses based on the input. Conclusion Both versions of ChatGPT provide reliable medical information, with the paid version offering more adaptable and readable responses. Healthcare providers can recommend ChatGPT as a source of patient education, regardless of the version used. Future research should explore diverse question formulations and ChatGPT's handling of incorrect information.

Unlocking Health Literacy: The Ultimate Guide to Hypertension Education From ChatGPT Versus Google Gemini.

Background Google Gemini (Google, Mountain View, CA) represents the latest advances in the realm of artificial intelligence (AI) and has garnered attention due to its capabilities similar to the increasingly popular ChatGPT (OpenAI, San Francisco, CA). Accurate dissemination of information on common conditions such as hypertension is critical for patient comprehension and management. Despite the ubiquity of AI, comparisons between ChatGPT and Gemini remain unexplored. Methods ChatGPT and Gemini were asked 52 questions derived from the American College of Cardiology's (ACC) frequently asked questions on hypertension, following a specified prompt. Prompts included: no prompting (Form 1), patient-friendly prompting (Form 2), physician-level prompting (Form 3), and prompting for statistics/references (Form 4). Responses were scored as incorrect, partially correct, or correct. Flesch-Kincaid (FK) grade level and word count were recorded. Results Across all forms, scoring frequencies were as follows: 23 (5.5%) incorrect, 162 (38.9%) partially correct, and 231 (55.5%) correct. ChatGPT showed higher rates of partially correct answers than Gemini (p = 0.0346). Physician-level prompts resulted in a higher word count across both platforms (p < 0.001). ChatGPT showed a higher FK grade level (p = 0.033) in physician-friendly prompting. Gemini exhibited a significantly higher mean word count (p < 0.001); however, ChatGPT had a higher FK grade level across all forms (p > 0.001). Conclusion To our knowledge, this study is the first to compare cardiology-related responses from ChatGPT and Gemini, two of the most popular AI chatbots. The grade level for most responses was collegiate level, which was above average for the National Institutes of Health (NIH) recommendations, but on par with most online medical information. Both chatbots responded with a high degree of accuracy, with inaccuracies being rare. Therefore, it is reasonable that cardiologists suggest either chatbot as a source of supplementary education.

Evaluating ChatGPT Responses on Thyroid Nodules for Patient Education.

Background: ChatGPT, an artificial intelligence (AI) chatbot, is the fastest growing consumer application in history. Given recent trends identifying increasing patient use of Internet sources for self-education, we seek to evaluate the quality of ChatGPT-generated responses for patient education on thyroid nodules. Methods: ChatGPT was queried 4 times with 30 identical questions. Queries differed by initial chatbot prompting: no prompting, patient-friendly prompting, 8th-grade level prompting, and prompting for references. Answers were scored on a hierarchical score: incorrect, partially correct, correct, or correct with references. Proportions of responses at incremental score thresholds were compared by prompt type using chi-squared analysis. Flesch-Kincaid grade level was calculated for each answer. The relationship between prompt type and grade level was assessed using analysis of variance. References provided within ChatGPT answers were totaled and analyzed for veracity. Results: Across all prompts (n = 120 questions), 83 answers (69.2%) were at least correct. Proportions of responses that were at least partially correct (p = 0.795) and correct (p = 0.402) did not differ by prompt; responses that were correct with references did (p < 0.0001). Responses from 8th-grade level prompting were the lowest mean grade level (13.43 ± 2.86) and were significantly lower than no prompting (14.97 ± 2.01, p = 0.01) and prompting for references (16.43 ± 2.05, p < 0.0001). Prompting for references generated 80/80 (100%) of referenced medical publications within answers. Seventy references (87.5%) were legitimate citations, and 58/80 (72.5%) provided accurately reported information from the referenced publication. Conclusion: ChatGPT overall provides appropriate answers to most questions on thyroid nodules regardless of prompting. Despite targeted prompting strategies, ChatGPT reliably generates responses corresponding to grade levels well-above accepted recommendations for presenting medical information to patients. Significant rates of AI hallucination may preclude clinicians from recommending the current version of ChatGPT as an educational tool for patients at this time.

An IL-2 mutein increases IL-10 and CTLA-4-dependent suppression of dendritic cells by regulatory T cells.

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3+ regulatory T (TR) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated TR population with elevated proliferation, a transcriptional program associated with Stat5- and TCR-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface MHC class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 costimulatory ligands from maturing cDCs to TR cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes resulting in T cell anergy. Thus, IL-2 mutein-expanded TR cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.

MDR1-EXPRESSING CD4+ T CELLS WITH TH1.17 FEATURES RESIST TO NEOADJUVANT CHEMOTHERAPY AND ARE ASSOCIATED WITH BREAST CANCER CLINICAL RESPONSE.

BACKGROUND: Multidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets in which it confers chemoresistance. Among human T cells, MDR1 is expressed by most CD8+ T cells, and a subset of CD4+ T helper (Th) cells. Here we explored the expression, function and regulation of MDR1 on CD4+ T cells and investigated the role of this population in response to neoadjuvant chemotherapy (NAC) in BC. METHODS: Phenotypic and functional characteristics of MDR1+ CD4 Th cells were assessed on blood from healthy donors and patients with BC by flow cytometry. These features were extended to CD4+ Th cells from untreated breast tumor by flow cytometry and RNA-sequencing (RNA-seq). We performed in vitro polarization assays to decipher MDR1 regulation on CD4 Th cells. We evaluated in vitro the impact of chemotherapy agents on MDR1+ CD4+ Th cells. We analyzed the impact of NAC treatment on MDR1+ CD4+ Th cells from blood and tumors and their association with treatment efficacy in two independent BC cohorts and in a public RNA-seq data set of BC tumor biopsies before and after NAC. Finally, we performed single cell (sc) RNAseq of blood CD4+ memory T cells from NAC-treated patients and combined them with an scRNAseq public data set. RESULTS: MDR1+ CD4 Th cells were strongly enriched in Th1.17 polyfunctional cells but also in Th17 cells, both in blood and untreated breast tumor tissues. Mechanistically, Tumor growth factor (TGF)-ß1 was required for MDR1 induction during in vitro Th17 or Th1.17 polarization. MDR1 expression conferred a selective advantage to Th1.17 and Th17 cells following paclitaxel treatment in vitro and in vivo in NAC-treated patients. scRNAseq demonstrated MDR1 association with tumor Th1.17 and Th with features of cytotoxic cells. Enrichment in MDR1+ CD4+ Th1.17 and Th17 cells, in blood and tumors positively correlated with pathological response. Absence of early modulation of Th1.17 and Th17 in NAC-resistant patients, argue for its use as a biomarker for chemotherapy regimen adjustment. CONCLUSION: MDR1 favored the enrichment of Th1.17 and Th17 in blood and tumor after NAC that correlated to clinical response.

Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

Evaluating ChatGPT responses on obstructive sleep apnea for patient education.

STUDY OBJECTIVES: We evaluated the quality of ChatGPT responses to questions on obstructive sleep apnea for patient education and assessed how prompting the chatbot influences correctness, estimated grade level, and references of answers. METHODS: ChatGPT was queried 4 times with 24 identical questions. Queries differed by initial prompting: no prompting, patient-friendly prompting, physician-level prompting, and prompting for statistics/references. Answers were scored on a hierarchical scale: incorrect, partially correct, correct, correct with either statistic or referenced citation ("correct+"), or correct with both a statistic and citation ("perfect"). Flesch-Kincaid grade level and citation publication years were recorded for answers. Proportions of responses at incremental score thresholds were compared by prompt type using chi-squared analysis. The relationship between prompt type and grade level was assessed using analysis of variance. RESULTS: Across all prompts (n = 96 questions), 69 answers (71.9%) were at least correct. Proportions of responses that were at least partially correct (P = .387) or correct (P = .453) did not differ by prompt; responses that were at least correct+ (P < .001) or perfect (P < .001) did. Statistics/references prompting provided 74/77 (96.1%) references. Responses from patient-friendly prompting had a lower mean grade level (12.45 ± 2.32) than no prompting (14.15 ± 1.59), physician-level prompting (14.27 ± 2.09), and statistics/references prompting (15.00 ± 2.26) (P < .0001). CONCLUSIONS: ChatGPT overall provides appropriate answers to most questions on obstructive sleep apnea regardless of prompting. While prompting decreases response grade level, all responses remained above accepted recommendations for presenting medical information to patients. Given ChatGPT's rapid implementation, sleep experts may seek to further scrutinize its medical literacy and utility for patients. CITATION: Campbell DJ, Estephan LE, Mastrolonardo EV, Amin DR, Huntley CT, Boon MS. Evaluating ChatGPT responses on obstructive sleep apnea for patient education. J Clin Sleep Med. 2023;19(12):1989-1995.

Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune-modifying therapies.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter the response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of patients with RA after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the cytotoxic T lymphocyte antigen 4-Ig therapy abatacept had reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At the cellular level, these patients showed reduced activation and class switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4+ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B cell-depleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in patients with RA on different immune-modifying therapies and help inform efforts to improve vaccination strategies in this vulnerable population.

Evaluating YouTube videos on sialendoscopy as an educational resource for patients.

Objectives: Patients are increasingly relying on YouTube for health information. We objectively evaluated the quality and comprehensiveness of sialendoscopy YouTube videos available to patients. We further investigated the relationship between video content and video popularity. Methods: We identified 150 videos using the search term "sialendoscopy." Videos were excluded if they were lectures for medical professionals, operating room (OR) recordings, unrelated, non-English, or non-audio. Video quality and comprehensiveness were evaluated using modified DISCERN criterion (range: 5-25) and novel sialendoscopy criterion (NSC, range: 0-7), respectively. Secondary outcomes included standard video metrics and Video Power Index to measure popularity. Videos were classified binarily by uploader type as from an academic medical center or from other sources. Results: Twenty-two (14.7%) of 150 videos were included for review, with 7 (31.8%) uploaded from academic medical institutions. One hundred-nine (72.7%) videos were excluded as lectures for medical professionals or OR recordings. Overall mean modified DISCERN (13.45 ± 3.42) and NSC (3.05 ± 0.96) scores were low; however, videos uploaded by academic medical institutions were significantly more comprehensive (NSC mean difference = 0.98, 95% CI: 0.16-1.80, p = .02). There were no significant correlations between video popularity and objective measures of quality or comprehensiveness. Conclusions: This study highlights the paucity and low quality of sialendoscopy videos for patients. More popular videos are not higher quality, and most videos are targeted more toward physicians rather than patients. As YouTube becomes increasingly used by patients, there is opportunity for otolaryngologists to produce more informative videos for patients while implementing targeted strategies to increase viewership. Level of Evidence: NA.

Septic Arthritis With Superimposed Acute Gouty Arthritis in a Rheumatoid Arthritis Patient.

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus (Streptococcus agalactiae) infection and monosodium urate crystals. A diagnosis of septic arthritis with superimposed acute gouty arthritis was made and the patient was treated accordingly. Management included surgical irrigation and debridement, antibiotic therapy, and systemic glucocorticoids which resulted in a significant improvement in the patient's clinical status.

Patient experiences of sialendoscopy with monitored anesthesia care versus general anesthesia.

OBJECTIVE: To compare the experiences of patients who received sialendoscopy under general anesthesia (GA) with those who received monitored anesthesia care (MAC). METHODS: Patients who underwent sialendoscopy for sialadenitis or sialolithiasis from July 1, 2020, to July 31, 2021, were offered inclusion to this prospective observational study. A survey was sent to consenting patients on post-operative day 1 to record aspects of their pre-, intra-, and post-operative experience. The primary outcome was overall satisfaction. Secondary outcomes included pain tolerability and preference for similar anesthetic modality in the future. RESULTS: Seventy-five patients completed the post-operative survey (86% response rate), of which 39 patients received GA and 36 received MAC. Patient overall satisfaction was similar between groups (GA: "Poor/Average/Good" = 23%, "Excellent" = 77%; MAC: "Poor/Average/Good" = 25%, "Excellent" = 75%, p = 1.00). Tolerability of immediate post-operative pain was likewise similar between the GA (82%) and MAC (97%) groups (p = 0.058). Patients who received MAC reported intra-operative pain as "none/tolerable" 72% of the time and "uncomfortable" 28% of the time. Patients who received GA would prefer the same anesthetic in the future more often than in the MAC group (85% versus 61%, respectively, OR 3.50, 95% CI 1.17-10.50, p = 0.035). CONCLUSION: In regard to patient satisfaction, both MAC and GA are acceptable anesthetic choices in sialendoscopy for appropriate cases. Patients report similar overall satisfaction and post-operative pain tolerance under either anesthetic modality. Patients who undergo GA report higher rates of preference for similar anesthetic modality in the future. Further study is needed to determine the most appropriate criteria for anesthesia modality selection.

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells.

Genome-wide association studies (GWASs) have uncovered hundreds of autoimmune disease-associated loci; however, the causal genetic variants within each locus are mostly unknown. Here, we perform high-throughput allele-specific reporter assays to prioritize disease-associated variants for five autoimmune diseases. By examining variants that both promote allele-specific reporter expression and are located in accessible chromatin, we identify 60 putatively causal variants that enrich for statistically fine-mapped variants by up to 57.8-fold. We introduced the risk allele of a prioritized variant (rs72928038) into a human T cell line and deleted the orthologous sequence in mice, both resulting in reduced BACH2 expression. Naive CD8 T cells from mice containing the deletion had reduced expression of genes that suppress activation and maintain stemness and, upon acute viral infection, displayed greater propensity to become effector T cells. Our results represent an example of an effective approach for prioritizing variants and studying their physiologically relevant effects.