Citations

Objective Specific sedative hypnotic agents, administered to facilitate endotracheal intubation (ETI) in critically ill adults, may lead to adverse outcomes such as peri-intubation cardiovascular collapse. However, little is known from systematic investigations of the impact these individual agents have on cardiovascular function or other clinical outcomes. Data sources MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, Scopus and Web of science databases. Study selection We conducted a systematic search for randomized and non-randomized studies that evaluated adult (≥18 years) critically ill patients who were sedated to facilitate ETI with ketamine, propofol, ketamine/propofol, etomidate, or a benzodiazepine and who had data on peri-intubation hemodynamics and at least one other outcome involving acute kidney injury, delirium, opioid use, intubation difficulty, sequential organ failure assessment, length of stay, or mortality. Eighty-five studies were identified for eligibility assessment with 23 included in the analysis. Data extraction Two reviewers independently screened articles, extracted data from selected articles, and assessed risk of bias using ROBINS-I for observational studies and revised Cochrane Risk of Bias tool for randomized controlled trials. Data synthesis Acute cardiovascular dysfunction (peri-intubation hemodynamic instability and/or cardiac arrest) was similar between etomidate and ketamine with more events seen when propofol versus non-propofol sedation was administered. However, exploratory meta-analysis demonstrated no difference between etomidate and ketamine (OR 1.05 [95%CI 0.60-1.84]) or between etomidate and propofol (OR 0.91 [95%CI 0.33-2.46]). Compared to ketamine, etomidate demonstrated lower survival to hospital discharge in the included studies in exploratory meta-analysis OR 0.76 (95%CI 0.62-0.92). Limited data existed for other outcomes with no discernible differences between sedative agents. Conclusions Acute cardiovascular dysfunction was more common when propofol, as compared to non-propofol sedation, was administered, although not statistically significant in exploratory meta-analysis. In addition, etomidate conferred lower survival to hospital discharge versus non-etomidate sedation, which was confirmed in exploratory meta-analysis of etomidate versus ketamine.

Abstract Introduction: Pulmonary sclerosing pneumocytoma, formerly known as sclerosing hemangioma, is an uncommon benign neoplasm most recently classified by the World Health Organization as an adenoma. It occurs most commonly in middle-aged women of East Asian descent, in whom it is most often discovered incidentally on imaging. It typically appears as a single, well-circumscribed lesion on CT that lacks specific defining characteristics and can appear similar to malignancies such as pulmonary adenocarcinoma. Therefore, diagnosis relies on histopathology. The tumor is derived from respiratory epithelial cells expressing TTF-1 in both round and surface cells, and immunohistochemistry (IHC) staining is positive for both TTF-1 and EMA. Description of Case: A 52-year-old female from Southeast Asia presented to primary care clinic reporting atypical chest pain. She denied shortness of breath, cough, fever, night sweats, or weight loss. She had no prior smoking history, but there was a remote history of chewing tobacco. Chest x-ray revealed a retrocardiac left lower lobe pulmonary nodule. CT chest was obtained and revealed a solid left lower lobe pulmonary nodule measuring 2.2 cm in diameter. The nodule was mildly FDG avid on subsequent PET-CT with SUVmax 2.8, noted to be suspicious for a lesion on the pulmonary adenocarcinoma spectrum. She opted for surgical removal and underwent thoracoscopic left lower lobe wedge resection. Pathology demonstrated sclerosing pneumocytoma with IHC stains positive for TTF1, EMA, and keratin AE1/AE3. The follow-up CT chest showed no evidence of local recurrence or residual tumor. Discussion: Pulmonary sclerosing pneumocytoma is an uncommon benign neoplasm of the lung that can be easily mistaken for malignancy such as pulmonary adenocarcinoma given its imaging characteristics and FDG avidity on PET-CT. It must be considered in the differential for lung nodules, particularly in middle-aged women of East Asian descent. Diagnosis is made with biopsy showing both cuboidal surface cells and stromal round cells, with IHC staining positively for TTF-1 and EMA. However, these tumors remain difficult to diagnose in frozen section, small biopsies, and cytology, because they are easily mistaken for adenocarcinoma or carcinoid tumors. The clinical course is generally benign, but very rarely there is metastasis or recurrence.

Objective To develop and validate classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by EULAR and the American College of Rheumatology (ACR). Methods This international initiative had 4 phases: (1) candidate items were proposed in a survey of pediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. Results The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anemia, C‐reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. Conclusion These new classification criteria for pediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol >1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI <30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P < 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

ABSTRACTBackgroundThis study investigates the association between thromboembolic events (TE) and castration‐resistant prostate cancer (CRPC) patients receiving oral androgen receptor pathway inhibitors (ARPi) compared to those undergoing chemotherapy, both with and without a pre‐existing history of cardiovascular disease (CVD).MethodsA total of 2779 men diagnosed with CRPC were identified using the Surveillance, Epidemiology, and End Results (SEER) Medicare Linked Database from 2012 to 2016. Patients were stratified based on their CVD history. Within each CVD stratum (pre‐existing CVD vs. no pre‐existing CVD), patients were further categorized into two treatment groups: those receiving oral ARPi and those undergoing chemotherapy. Unadjusted and inverse probability treatment weight (IPTW)‐adjusted proportional hazards models, using Fine and Gray's method, were applied to evaluate the potential association between ARPi treatment and TE.ResultsPatients with pre‐existing CVD treated with ARPi exhibited a significantly lower crude hazard ratio (HR) for TE compared to chemotherapy (HR 0.39, 95% CI 0.27–0.58, p < 0.001). However, after adjustment using IPTW, this association was no longer significant (adjusted hazard ratio [AHR] 1.00, 95% CI 0.75–1.32, p = 0.99). For patients without CVD, ARPi use was also associated with a reduced risk of TE in the crude analysis (HR 0.53, 95% CI 0.32–0.87, p = 0.01), but this effect was not statistically significant after IPTW adjustment (HR 0.99, 95% CI 0.69–1.41, p = 0.94).ConclusionARPi demonstrated no significant effect on TE risk compared to chemotherapy, regardless of pre‐existing CVD status. Similarly, when excluding patients with a prior history of TE, ARPi use remained non‐significantly associated with new TE in the IPTW‐adjusted competing risk analysis, highlighting the need for further investigation.

Abstract Background/Aims Fibromyalgia has many unmet needs relating to treatment and delivery of effective and evidence-based healthcare is lacking. We analyzed social media conversations to understand patients’ perspectives of the lived experience of fibromyalgia, factors reported to trigger flares of pain, treatments being discussed; and identify barriers and opportunities to improve healthcare delivery. Methods A non-interventional retrospective analysis accessed detail rich conversations about fibromyalgia patients’ experiences with data curated from 400 million global documents and 714,000 documents, including a fibromyalgia language tag, between May 2019 and April 2021. Data were analyzed via qualitative and quantitative analyses. Results Fibromyalgia conversations were most numerous on Twitter and Reddit and conversations trends remained stable over time. There were numerous environmental and modifiable triggers ranging from (most frequently) stress and anxiety to various foods. Arthritis and irritable bowel syndrome (IBS) were the most frequently associated comorbidities. Patients with fibromyalgia reported a wide range of symptoms, with pain a cardinal feature. Massage, meditation and acupuncture domains were the most reported treatment modalities. Opportunities to improve healthcare delivered by medical providers were identified with current frustration relating to lack of acknowledgement of their disease, minimization of symptoms, and providers inadequately meeting their care needs. Conclusion We developed a comprehensive large-scale study which emphasizes advanced artificial intelligence algorithms application in real-world research design. Through the extensive encapsulation of patient perspectives, we have outlined habitual symptoms, triggers, and treatment modalities that provide a durable foundation to address gaps in healthcare provision. Disclosure L. Bell: Other; Lucy Bell was a former contractor based at Black Swan Data, and a volunteer at White Swan. She is currently a full-time employee at White Swan. B. Fordham: Other; Beth Fordham is an employee of White Swan Charity, who provided the dataset for this study, and was previously an employee of Black Swan Data, of which White Swan is a separate entity. S. Mumtaz: None. R. Yaman: None. L. Balistreri: None. R.R. Butendieck: None. A. Irani: None.

Abstract Background: Chromosomal instability (CIN) is frequent in patients with metastatic castration-resistant prostate cancer (mCRPC) and determines taxane resistance. A circulating tumor cell (CTC) assay which morphologically identifies CTCs with CIN (CTC-CIN) from a single tube of whole blood could predict clinical outcomes in this population. We tested this hypothesis as a pre-planned, secondary outcome of the CARD trial, where patients with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate + prednisolone/prednisone) were randomized to treatment with cabazitaxel or the alternative ARPI. Methods: CTCs were isolated from blood samples obtained at baseline; cycle two, and end of treatment. The associations of baseline CTC and counts with imaging-based progression free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate (PRR) were assessed. Results: Of 255 patients randomized, CTC counts were acquired from 237 patients at screening, 213 patients at C2D1, and 166 patients at EOT. High baseline CTC counts were significantly associated with worse OS (median OS, 14.9 vs 9.8 months; univariate HR, 1.81; 95% CI, 1.30 - 2.51; p &lt; 0.001). High baseline CTC-CIN counts were significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs 8.9 months; univariate HR, 2.16; 95% CI, 1.52 - 3.06; p &lt; 0.001; multivariate HR, 1.56; 95% CI, 1.01 - 2.43; p = 0.047). Low CTC-CIN at baseline predicted ibPFS, ORR, and PRR benefit with cabazitaxel; conversely, high at baseline predicted no different ibPFS or OS outcomes with cabazitaxel or a second ARPI. Conclusions: This preplanned biomarker analysis of CARD confirmed that CTC-CIN counts are prognostic for OS and may be predictive of cabazitaxel benefit. (Funded by Sanofi and Epic Sciences; CARD ClinicalTrials.gov number, NCT02485691.) Citation Format: Ossian Longoria, Jan Rekowski, Santosh Gupta, Nick Beije, Klaus Pantel, Eleni Efstathiou, Cora Sternberg, Daniel Castellano, Karim Fizazi, Bertrand Tombal, Adam Sharp, Oliver Sartor, Sandrine Mace, Christine Geffriaud-Ricouard, Richard Wenstrup, Ronald de Wit, Johann de Bono. Morphological evaluation of chromosomal instability in circulating tumor cells and prediction of taxane resistance in metastatic prostate cancer: a prespecified sub-analysis of the CARD trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1145

Abstract Increased innate immune activity promotes neurodegeneration and contributes to progression in multiple sclerosis. This prospective case-control study aims to investigate thalamic microglia density on 18kDa translocator protein PET in patients with multiple sclerosis using a third-generation radioligand, 11C-ER176, and investigate the associations of 11C-ER176 PET uptake with imaging and clinical measures of progression in multiple sclerosis. Patients with multiple sclerosis (n = 50) and controls (n = 55) were prospectively enrolled and they underwent 11C-ER176 PET and MRI including diffusion MRI with neurite orientation dispersion and density imaging. Disease characteristics, expanded disability status scale and multiple sclerosis functional composite scores were obtained in patients with multiple sclerosis. Age at imaging (mean ± standard deviation: patients = 49.6 ± 12.9 years, controls = 48.2 ± 15.4 years, P = 0.63) and sex (female ratio; patients = 72%, controls = 65%, P = 0.47) were not different between the groups. Thalamus 11C-ER176 PET uptake was highest in patients with progressive multiple sclerosis (1.272 ± 0.072 standardized uptake value ratio), followed by patients with relapsing multiple sclerosis (1.209 ± 0.074 standardized uptake value ratio) and lowest in controls (1.162 ± 0.067 standardized uptake value ratio, P &lt; 0.001). Patients with thalamic lesions had higher thalamus 11C-ER176 PET uptake than those without thalamic lesions in both relapsing multiple sclerosis and progressive multiple sclerosis (P &lt; 0.001). In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake correlated with lower thalamic volume (r = −0.45, P = 0.001), higher mean diffusivity (r = 0.56, P &lt; 0.001), lower neurite density index (r = −0.43, P = 0.002), lower orientation dispersion index (r = −0.40, P = 0.005) and higher free water fraction (r = 0.42, P = 0.003) in the thalamus. In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake also correlated with higher mean diffusivity (r = 0.47, P &lt; 0.001) and lower neurite density index (r = −0.36, P = 0.012) in the corpus callosum. In patients with multiple sclerosis, higher thalamus 11C-ER176 PET uptake correlated with worse expanded disability status scale scores (r = 0.33, P = 0.02), paced auditory serial addition test scores (r = −0.43, P = 0.003) and multiple sclerosis functional composite z-scores (r = −0.46, P = 0.001). Microglia density in the thalamus is highest in patients with progressive multiple sclerosis and is associated with imaging biomarkers of neurodegeneration and clinical disease severity. As a signature imaging biomarker of progression in multiple sclerosis, effectively reflecting the global disease burden, 11C-ER176 PET may aid development and efficacy evaluation of therapeutics targeting microglia.