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Chronic Marijuana Use and Chronic Obstructive Pulmonary Disease: A Case Report.
No full textMarijuana smoking has become increasingly common in the United States and the world as more states and countries have legalized it for medical and recreational use. There are a number of carcinogens in marijuana smoke similar to those in tobacco smoke, and yet it has been difficult in the literature to find a causal relationship between marijuana smoking and chronic obstructive pulmonary disease (COPD). We present a patient whose main risk factor for emphysema is daily marijuana smoking for upwards of 35 years with no personal history of smoking tobacco, and no other obvious risk factors. Current studies have shown association with chronic marijuana smoking and various lung complaints, forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio, and inconsistently with chronic bronchitis. With this case, we add to the current body of literature that suggests a possible relationship between long-term, heavy marijuana use and COPD
Effects of empagliflozin on quality of life and healthcare use and costs in chronic kidney disease: a health economic analysis of the EMPA-KIDNEY trial.
No full textBACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) slow progression of chronic kidney disease (CKD) but there is no randomised evidence of their effects on health-related quality of life (QoL) and healthcare use. We explored the effects of empagliflozin on health-related QoL, healthcare use and UK healthcare costs in the EMPA-KIDNEY trial.
METHODS: EMPA-KIDNEY, a randomised, double blind, placebo-controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included participants aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to \u3c 45 mL/min/1.73 m
FINDINGS: Between May 15, 2019 and April 16, 2021, 6609 participants were randomly assigned to empagliflozin (3304 participants) or matching placebo (3305 participants) in the active-trial which lasted for a median of 2.0 years. Among them, 4891 (74%) were enrolled in the post-trial follow-up. Per participant allocated to empagliflozin over 2 years, total empagliflozin cost was £826 (95% confidence interval: 818 to 835), QALYs were 0.012 higher (0.001 to 0.022), with less cost for hospital admission (-£239, -449 to -29), concomitant medications (-£130, -214 to -47), and management of ESKD (-£208, -414 to -2) compared to placebo. Over a further 2 years of post-trial follow-up off study treatment, there were additional per participant ESKD cost savings (-£842, -1441 to -242), resulting in net total healthcare cost of -£593 (-1384 to 198) over 4 years. The probability of 2 years of empagliflozin treatment being cost-effective at £20 K threshold in the UK was 43% over 2 years of follow-up and 91% over 4 years. The relative effects of empagliflozin on each cost component were similar across categories by baseline levels of eGFR, uACR and diabetes status, with larger reductions in healthcare costs estimated in categories at higher risk of CKD progression.
INTERPRETATION: In EMPA-KIDNEY, 2 years treatment with empagliflozin improved QALYs, and reduced use and cost of other healthcare, resulting in high likelihood of cost-effectiveness across a broad range of patients with CKD. The study\u27s key limitation is its relatively short active treatment period and follow-up duration, which may lead to underestimation of the cost-effectiveness of long-term SGLT2i treatment in CKD.
FUNDING: Boehringer Ingelheim, Germany; Eli Lilly, USA; Medical Research Council, UK; British Heart Foundation, UK; Health Data Research, UK; National Institute for Health and Care Research, UK
Phase II trial of nilotinib in PDGFR-alpha-enriched recurrent high-grade gliomas.
No full textBackground: This phase II clinical trial evaluated the safety and efficacy of nilotinib in patients with recurrent, platelet-derived growth factor receptor alpha (PDGFRA)-enriched high-grade gliomas.
Methods: Thirty-four adult patients with PDGFRA-enriched recurrent high-grade gliomas were enrolled. Study treatment consisted of nilotinib 400 mg administered twice daily in 28-day cycles. Safety and clinical activity were evaluated.
Results: Median lines of prior therapy were 2 (range 1-7) and 9 of 34 (26%) patients received prior bevacizumab. Four patients had PDGFRA gene amplification, and 30 had PDGFRA overexpression by immunohistochemistry. Overall, nilotinib was well tolerated. The most common treatment-related toxicities were increased ALT, joint pain, and hyponatremia. No treatment-related grade 4 or 5 adverse events occurred. The best response was stable disease (SD) for 8 patients and complete response (CR) for one patient with glioblastoma. The median PFS was 1.45 months (95% CI 0.986-2.07) and the median OS was 6.6 months (95% CI 4.9-18.3). The patient with a CR was an MGMT-unmethylated GBM with PDGFRA overexpression by IHC, and maintained a durable response for over 5 years.
Conclusion: Nilotinib was well tolerated with limited benefit in this enriched population of patients. Further studies are warranted to determine the clinical benefit in patients in earlier lines of treatment. Trial registration number: NCT01140568, registered 08 June 2010
Preclinical evaluation of a novel 8-spline pulsed field ablation system.
No full textBACKGROUND: Pulsed field ablation (PFA) technologies offer the potential for improved procedural efficacy and safety. Circumferential pulmonary vein (PV) ablation approaches are attractive compared with point-by-point, simplifying workflow.
OBJECTIVE: We evaluated the safety and efficacy of a novel, over-the-wire, balloon-based basket-shaped catheter achieving rapid, durable PV isolation (PVI) with a simple workflow.
METHODS: PFA was delivered to the right superior, right inferior, left superior, and left inferior PVs in 18 male canines (25-45 kg). There were 3 groups of 6 animals that survived for 34 ± 4 days. Group 1 (low voltage, 3 applications) also included a safety challenge in which PFA was applied in the superior vena cava directly adjacent to the phrenic nerve. Group 2 (nominal voltage, 8 applications) represents the maximum recommended dose, completed with the esophagus deviated to the left atrial posterior wall and used for PV stenosis assessment. Group 3 (nominal voltage, treated until PVI, 2-8 applications) represents the standard settings for ablating the PVs in a clinical workflow.
RESULTS: All animals survived, showed no significant PV stenosis nor esophageal injury, and retained phrenic nerve pace capture ≥30 minutes after PFA and 30 days. At 30 days, 90.9% (n = 20 of 22) in group 1, 100% (n = 23 of 23) in group 2, 95.2% (n = 20 of 21) in group 3, and 95.5% (n = 63 of 66) overall demonstrated bidirectional PV block. Histopathologic assessment revealed transmural fibrotic lesions with evidence of vessel sparing, but absence of tissue necrosis and thrombus. The esophagi and main coronary arteries were grossly and microscopically normal with no evidence of coronary artery stenosis. Other collateral tissue damage and embolic lesions were minimal and clinically insignificant.
CONCLUSION: This novel PFA system demonstrated effective and durable chronic PVI over a range of PFA amplitudes and applications with favorable usability and an optimal safety profile
Announcing the Biomedical Data Translator: Initial Public Release.
No full textThe growing availability of biomedical data offers vast potential to improve human health, but the complexity and lack of integration of these datasets often limit their utility. To address this, the Biomedical Data Translator Consortium has developed an open-source knowledge graph-based system-Translator-designed to integrate, harmonize, and make inferences over diverse biomedical data sources. We announce here Translator\u27s initial public release and provide an overview of its architecture, standards, user interface, and core features. Translator employs a scalable, federated, knowledge graph framework for the integration of clinical, genomic, pharmacological, and other biomedical knowledge sources, enabling query retrieval, inference, and hypothesis generation. Translator\u27s user interface is designed to support the exploration of knowledge relationships and the generation of insights, without requiring deep technical expertise and gradually revealing more detailed evidence, provenance, and confidence information, as needed by a given user. To demonstrate Translator\u27s application and impact, we highlight features of the user interface in the context of three real-world use cases: suggesting potential therapeutics for patients with rare disease; explaining the mechanism of action of a pipeline drug; and screening and validating drug candidates in a model organism. We discuss strengths and limitations of reasoning within a largely federated system and the need for rich concept modeling and deep provenance tracking. Finally, we outline future directions for enhancing Translator\u27s functionality and expanding its data sources. Translator represents a significant step forward in making complex biomedical knowledge more accessible and actionable, aiming to accelerate translational research and improve patient care
Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction.
No full textThe colonic epithelium plays a key role in the host-microbiome interactions, allowing uptake of various nutrients and driving important metabolic processes. To unravel detailed metabolic activities in the human colonic epithelium, our present study focuses on the generation of the first cell-type-specific genome-scale metabolic model (GEM) of human colonic epithelial cells, named iColonEpithelium. GEMs are powerful tools for exploring reactions and metabolites at the systems level and predicting the flux distributions at steady state. Our cell-type-specific iColonEpithelium metabolic reconstruction captures genes specifically expressed in the human colonic epithelial cells. iColonEpithelium is also capable of performing metabolic tasks specific to the colonic epithelium. A unique transport reaction compartment has been included to allow for the simulation of metabolic interactions with the gut microbiome. We used iColonEpithelium to identify metabolic signatures associated with inflammatory bowel disease. We used single-cell RNA sequencing data from Crohn\u27s Diseases (CD) and ulcerative colitis (UC) samples to build disease-specific iColonEpithelium metabolic networks in order to predict metabolic signatures of colonocytes in both healthy and disease states. We identified reactions in nucleotide interconversion, fatty acid synthesis and tryptophan metabolism were differentially regulated in CD and UC conditions, relative to healthy control, which were in accordance with experimental results. The iColonEpithelium metabolic network can be used to identify mechanisms at the cellular level, and we show an initial proof-of-concept for how our tool can be leveraged to explore the metabolic interactions between host and gut microbiota
Prehospital cardiac arrest resuscitation practices differ around the globe.
No full textBACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. This study aims to describe the international variations in the practices related to the initiation, termination, and refraining from resuscitation of adult patients (≥18 years) with a non-traumatic OHCA.
METHODS: An exploratory descriptive study was conducted using a cross-sectional online survey. The respondents were recruited using snowball sampling technique. Framework analysis was used to identify key themes in responses, with descriptive statistics summarising data trends.
RESULTS: The study collected responses from 59 countries. Our findings reveal that respondents from 59.3% of countries reported that they initiate resuscitation in all cases where the patients do not show obvious signs of irreversible death or do not have confirmed advance directives. Respondents from 15.3% of countries reported that once started, prehospital resuscitation attempts are not terminated. Prehospitally respondents from 20.3% of the countries reported that they rely exclusively on specific criteria to decide when to terminate resuscitation efforts while in 45.8%, these decisions are made at the discretion of the provider. Respondents from most countries (91.5%) reported that they refrain from resuscitation in the presence of obvious signs of irreversible death. Respondents from 57.6% of countries, reported that they refrained from resuscitation if the patient had a confirmed do-not-attempt-cardiopulmonaryresuscitation (DNACPR), while 15.3% mentioned staff safety as a reason to abstain from attempting resuscitation.
CONCLUSION: This study reveals global variation in EMS resuscitation practices, reflecting disparities in resources, healthcare infrastructure, EMS system design, community acceptability given cultural and societal norms, and legislation
Prognostic Features of Recurrent Midline and H3 K27M-Mutant Glioma.
No full textBackground/Objectives: Midline glioma is a frequently morbid primary brain tumor often characterized by the histone mutation H3 K27M. The standard-of-care treatment is radiation therapy in the frontline setting, though effective treatment remains elusive and there is no established therapy in the second line or later setting. Here, we present the results of a multicenter, observational, retrospective study of the natural history of this disease in the recurrent setting when managed via standard-of-care interventions. Methods: Forty-four patients with recurrent H3 K27M-mutant and/or midline glioma after standard-of-care treatment were identified across 11 clinical centers in the United States who met inclusion criteria for evaluation. Data collected were analyzed by tumor radiographic appearance, age, anatomic location, and H3 K27M status, with factors contributing to overall survival (OS) identified. Results: Overall, median OS from time of first recurrence was 5.1 months (95% CI, 3.9 to 7.7%). In a subgroup analysis, survival was dismal across primary tumor locations, with a median OS of 3.7 months (95% CI: 0.7 to 9.8 months), 3.5 months (95% CI, 0.9 to not reached) for primary spinal, 5.1 months (95% CI to 0.2 not reached) for primary infratentorial, and 5.9 months (95% CI 4.4 to 14.7) for primary supratentorial tumors. In a multivariate analysis, DIPG and primary spinal tumor were associated with a higher risk of death. Conclusions: Taken together, these results shed light on prognostic factors and natural disease progression overtly related to recurrent midline and/or H3 K27M-mutant diffuse glioma, providing insight that can prove valuable for development of future clinical treatments for this recently defined disease
Acute Airway Compromise Due to Suspected Fishbone Ingestion.
No full textA 68-year-old woman presented to the emergency department (ED) with acute respiratory distress following suspected fishbone ingestion. The patient exhibited significant respiratory distress, and a video laryngoscope evaluation revealed bleeding and edema around the vallecula and arytenoid soft tissues, raising concerns for impending airway compromise. The patient was intubated and admitted to the intensive care unit (ICU) for further management. A soft tissue neck computed tomography scan revealed a fishbone lodged in the mid-esophagus, prompting a gastroenterology consultation for endoscopy. The endoscopy successfully removed the fishbone without complications. After the procedure, the patient remained stable and was monitored in the ICU. This case underscores the importance of early airway intervention in suspected foreign body ingestion and illustrates the role of prompt imaging and multidisciplinary management in ensuring favorable outcomes. Fortunately, the course following intervention was uneventful, and the patient was discharged with no further complications, highlighting the critical role of early intervention and careful management in preventing respiratory failure or other serious sequelae associated with foreign body ingestion
