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CT Imaging for Valvular Interventions
No full textPhysician-led computed tomography (CT) imaging for valvular interventions has directly contributed to the safety and scalability of transcatheter aortic valve interventions globally. As the shift of the global population\u27s valvular heart disease extends into the transcatheter aortic, mitral, pulmonic, and tricuspid space, CT imaging for valvular interventions in new anatomical pathophysiologies becomes more important than ever. Health systems dedicated to investing in physician-led structural heart imaging CT procedural planning expertise and transcatheter treatment advancements can bring life-saving innovative care to patients in need
Risk stratification using the SCAI SHOCK classification in patients with acute pulmonary embolism
No full textBACKGROUND: Pulmonary embolism (PE) is a leading cause of cardiovascular mortality, with high-risk cases exhibiting significant heterogeneity in treatment and outcomes. Existing classification systems fail to differentiate PE patients requiring vasopressor support from those experiencing cardiac arrest. This study applies the Society for Cardiovascular Angiography and Interventions (SCAI) shock classification to stratify high-risk PE patients and assess mortality differences.
METHODS: Utilizing the Nationwide Inpatient Sample (NIS) database (2017-2020), we identified adult PE hospitalizations classified by SCAI shock stages: Stage A/B (hemodynamically stable or hypotensive without vasopressors), Stage C/D (requiring vasopressors and/or mechanical circulatory support [MCS]), and Stage E (out-of-hospital cardiac arrest [OHCA]). Outcomes included mortality, treatment modality, and complications. Multivariate logistic regression models were used to adjust for confounders.
RESULTS: Among 853,160 PE admissions, 5770 (0.68 %) were Stage C/D and 15,825 (1.86 %) were Stage E. Mortality increased with shock severity: 2.13 % (Stage A/B), 39.90 % (Stage C/D), and 65.95 % (Stage E) (p \u3c 0.05). Mortality was lowest with surgical thrombectomy (17.24 % Stage C/D; 48.28 % Stage E) and highest with systemic thrombolysis (42.57 % Stage C/D; 70.62 % Stage E) (p \u3c 0.05). Adjusted odds of mortality were 13.9 (95 % CI: 11.9-16.2, p \u3c 0.05) for Stage C/D and 54.8 (95 % CI: 49.3-61.0, p \u3c 0.05) for Stage E.
CONCLUSION: Applying the SCAI shock classification to high-risk PE stratifies mortality risk more precisely. Patients with cardiac arrest exhibit significantly higher mortality than those requiring vasopressors alone. Future studies should explore refined risk stratification integrating hemodynamic parameters and biomarkers to optimize treatment selection
Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (PE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161
No full textPURPOSE: Nivolumab showed durable responses in patients with small cell lung cancer (SCLC). A randomized phase II study investigating nivolumab plus cisplatin/carboplatin and etoposide (PE) versus PE for patients with untreated extensive-stage (ES) SCLC was conducted.
METHODS: Patients with untreated ES-SCLC, Eastern Cooperative Oncology Group performance status 0-1, were randomized 1:1 to nivolumab 360 mg intravenously (IV) plus cisplatin 75 mg/m
RESULTS: Overall, 160 patients were enrolled; 144 patients were treated and constituted the primary analysis. The median PFS was 5.5 months (95% confidence interval [CI], 4.3-5.9 months) on arm A, and 4.9 months (95% CI, 4.5-5.7 months) on arm B (hazard ratio, 0.78; p = .083). The estimated median OS was 11.2 months (95% CI, 8.8-14.2 months) on arm A and 8.1 months (95% CI, 7.2-9.6 months) on arm B (hazard ratio, 0.71; p = .059).
CONCLUSION: The combination of PE and nivolumab improves both PFS and OS for patients with ES-SCLC. No new safety signals were observed
Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components
No full textExtracellular vesicles (EVs) facilitate the transfer of biological materials between cells throughout the body. Mitochondria, membrane-bound organelles present in the cytoplasm of nearly all eukaryotic cells, are vital for energy production and cellular homeostasis. Recent studies highlight the critical role of the transport of diverse mitochondrial content, such as mitochondrial DNA (mt-DNA), mitochondrial RNA (mt-RNA), mitochondrial proteins (mt-Prots), and intact mitochondria by small EVs (\u3c 200 nm) and large EVs (\u3e200 nm) to recipient cells, where these cargos contribute to cellular and mitochondrial homeostasis. The interplay between EVs and mitochondrial components has significant implications for health, metabolic regulation, and potential as biomarkers. Despite advancements, the mechanisms governing EV-mitochondria crosstalk and the regulatory effect of mitochondrial EVs remain poorly understood. This review explores the roles of EVs and their mitochondrial cargos in health and disease, examines potential mechanisms underlying their interactions, and emphasizes the therapeutic potential of EVs for neurological and systemic conditions associated with mitochondrial dysfunction
Profiling Glioma Stem Cell Dynamics via 3D-Based Cell Cycle Reporter Assays
No full textSuccessful containment of unwanted cell cycle progression in tumors such as glioblastoma (GBM) requires targeted therapeutic approaches, which rely on understanding cell cycle dynamics in response to microenvironmental stimuli. Glioma Stem Cells (GSCs) can drive tumor initiation, recurrence, therapy resistance, and are often attributed to the heterogeneity and plasticity of GBM. In vitro models, using patient-derived GSCs, provide a life relevant tool for exploration of complex molecular mechanisms underlying the aggressive characteristics of GBM. Introduction of 3D tissue culture systems permits the study of spatial complexity of the tumor mass and enables control over diverse conditions within the surrounding microenvironment. This chapter demonstrates detailed methods to study spatiotemporal changes to the cell cycle dynamics using available fluorescent cell cycle reporter systems in combination with bioinformatics-based signal intensity and localization analysis. We present a successful approach that investigates the 3D cell cycle dynamics of GSC populations. This approach utilizes GBM neurosphere and organoid cultures, which are assessed over time and under therapeutic pressure. These models can be further explored, manipulated, and customized to serve specific experimental designs
Clinical Features and ICHD Headache Diagnoses for Patients With Prominent Craniofacial Pain Referred by a Rhinologist to Headache Specialists
No full textOBJECTIVES: Most patients diagnosed with sinus headache are misdiagnosed and mistreated. These patients are often referred to otolaryngology for sinus disease evaluation. However, collaborations between rhinologists and headache specialists for sinus headaches have not been investigated. This study aimed to report the clinical features and headache diagnoses of patients referred to headache specialists for prominent craniofacial pain.
METHODS: We conducted a retrospective study of patients presenting with craniofacial pain to rhinologists and subsequently referred to a headache specialist for presumed, nonsinogenic, craniofacial pain. Records from a total of 98 patients were reviewed, and information regarding demographics, gender, nasal endoscopy findings, SNOT-22 (Sino-Nasal Outcome Test-22 questionnaire) score, ICHD (International Classification of Headache Disorders) headache diagnosis, and headache characteristics were extracted.
RESULTS: Nasal endoscopies performed by the rhinologists were normal in 92.7% of patients, edema was noted in 5.2% of patients, and mucopurulence in 2% of patients. The majority of patients described their pain as frontal or frontal-maxillary, dull or throbbing, and moderate to severe. Migraine was the most common final diagnosis in 49.1% of patients and the second most common diagnosis was tension-type headache in 17.3%. The remaining patients were diagnosed with 11 additional ICHD diagnoses.
CONCLUSIONS: Patients referred from a rhinologist to a headache specialist for nonsinogenic craniofacial pain are frequently diagnosed with primary headache disorder, specifically migraine or tension-type headache. Collaboration between specialists may improve diagnostic accuracy and outcomes, although further studies are crucial
Navigating an atypical presentation of peripheral stent infection: A case report of successful surgical salvage
No full textEndovascular stent infections are a rare but potentially devastating complication that often present with nonspecific generalized signs and symptoms, leading to delayed diagnosis. We describe the case of a 46-year-old woman who developed progressive weakness and a diffuse rash of the left lower extremity 1 week after a left external iliac artery bare metal stent was placed for lifestyle-limiting claudication. Blood cultures were positive, and computed tomography angiography revealed fluid collection around the stent suggestive of infection. Despite targeted antibiotic therapy, her symptoms persisted, necessitating surgical stent explantation and arterial reconstruction with a cryograft. Postoperatively, she achieved full resolution of symptoms. This case underscores the diagnostic and therapeutic challenges of endovascular stent infections and highlights the importance of early recognition and intervention
Cockroach immunotherapy modulates dominant T cell responses independent of allergen extract content
No full textBACKGROUND: T cell responses to the individual components of allergen extracts have not been fully elucidated in subcutaneous allergen immunotherapy (SCIT). Specifically, it is unknown whether T cell responses to immunodominant allergens are more or less sensitive to modulation, and whether allergen abundance in the immunotherapy extract influences T cell response modulation.
OBJECTIVE: To fill these gaps, we evaluated CD4+ T cell reactivity specific to each of the main cockroach (CR) allergens in the double-blinded, placebo controlled, multi-center CRITICAL SCIT trial.
METHODS: Participants (8-17 years) with mild to moderate, well controlled asthma, received 12-month dosing of CR SCIT (n=20) or placebo (n=26). Peripheral blood mononuclear cells (PBMC) were isolated prior to, and after 12 months of therapy. CD4+ T cell responses at baseline and after treatment were assessed using overlapping peptide pools derived from 11 well-defined CR allergens and intracellular cytokine staining for IL-4, IFNγ and IL-10 production. T cell responses were evaluated for magnitude, cytokine polarization, allergen immunodominance and correlation with allergen content in the CR SCIT extract.
RESULTS: SCIT modulation was more prominent in participants with the strongest and most Th2 polarized responses. Down-modulation was observed against Bla g 5 and Bla g 9, the most dominantly recognized allergens in the population study. Furthermore, effective modulation was observed independent of allergen content in the CR SCIT extract.
CONCLUSION: Our results suggest that immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT
Microbial safety of vapocoolant spray on sites for arterial line and epidural placement
No full textThis investigation evaluated if skin sterility is maintained following application of Gebauer\u27s Ethyl Chloride(®) vapocoolant spray. In this prospective, blinded, controlled study, the medial forearm (site of arterial line placement) and lower back (site of epidural placement) were swabbed before and after sterilisation and treatment with vapocoolant. Data were collected from 72 participants. There was no difference in microbial abundance between samples obtained from the wrist with ChloraPrep™ versus ChloraPrep + Gebauer\u27s Ethyl Chloride (P\u3e0.99), or in positive cultures (P=0.317). On the lower back, there was no difference in microbial abundance following ChloraPrep versus ChloraPrep + Gebauer\u27s Ethyl Chloride (P=0.317), or in positive cultures (P=0.317). Supply chain shortages of lidocaine have prompted consideration of alternative local anaesthetics. These findings support use of Gebauer\u27s Ethyl Chloride as an alternative to lidocaine for minimally invasive procedures such as placement of arterial lines and epidurals. Further investigation is necessary to explore the safety of vapocoolants in more invasive procedures
Feasibility of the Minimally Invasive Lumbar Decompression Procedure in a Lumbar Stenosis Patient With Radiographic Evidence of Spinal Instability
No full textLumbar spinal stenosis (LSS) can be challenging to treat in certain patient populations, particularly in patients for whom medical management is ineffective and surgical interventions carry a high risk of complications. This case report describes an 83-year-old woman with rheumatoid arthritis and LSS who presented with neurogenic claudication. Diagnosis was confirmed by physical examination and imaging, revealing canal stenosis and lumbar instability. Conservative measures failed to improve her symptoms, and she was deemed a poor surgical candidate given her age, advanced arthritis, and her current immunotherapy. Despite lacking supporting evidence, spinal instability has been considered a contraindication for minimally invasive lumbar decompression (MILD). However, following a multidisciplinary discussion, MILD was offered to the patient as a treatment option. To our knowledge, this is the first case of MILD in a patient with lumbar instability, resulting in sustained pain relief lasting over a year