Precision mRNA Nanomedicine for Targeted Vascular Therapies in ARDS & Atherosclerosis
https://www.science.org/content/article/new-nanoparticle-therapies-target-two-major-killers
https://www.biorxiv.org/content/10.1101/2025.01.09.632179v1
https://news.ycombinator.com/item?id=43535352

Nanoparticle therapies target two major killers
* ARDS: acute respiratory distress syndrome
* atherosclerosis

#nanoparticles #mRNA #ARDS #RespiratoryDistress #VascularDisease #atherosclerosis

Mhm ob cash wirklich gegen #ards hilft?🤔

https://en.m.wikipedia.org/wiki/Acute_respiratory_distress_syndrome

But yes, it's #BusinessAsUsual because #Crapitalism requires people to #ConsumeConsumeConsume!

Canadian teen with #BirdFlu was on #LifeSupport, new report reveals

The hospitalized teen was also given three #antiviral treatments, underscoring how severe #H5N1 infection can be

By Nicole Karlis, January 6, 2025

"In November, a teenager in British Columbia was infected and hospitalized with bird flu, caused by the H5N1 virus. While most cases have been mild, commonly characterized by #conjunctivitis and respiratory symptoms, this previously healthy Canadian teen was hospitalized from the virus in critical condition. Their symptoms started with double conjunctivitis, also known as pink eye, and turned into a fever and coughing. A few days later the teenager was admitted to intensive care after developing acute respiratory distress syndrome [#ARDS].

"'This was a healthy teenager prior to this, so no underlying conditions,' said British Columbia’s health officer, Bonnie Henry, at a news conference at the time. 'It just reminds us that in young people this is a virus that can progress and cause quite severe illness.'

"Now, a recent report brings to light more details about the teenager’s case. In the report, published in the New England Journal of Medicine (NEJM), researchers explain that the 13-year-old girl spent weeks fighting for her life after contracting a severe H5N1 infection from an unknown source. In finding her diagnosis, researchers say that she initially tested positive for influenza A, but not the seasonal subtype. Further testing suggested she had a high viral load of a novel influenza A infection, which researchers discovered to be the H5N1 avian flu.

"The next day doctors started her on oseltamivir, also known under the brand name Tamiflu. However, her respiratory functions declined rapidly causing her to be intubated. She was also placed on extracorporeal membrane oxygenation (ECMO), a machine that is a form of life support for people with life-threatening illnesses. In addition to the ECMO machine, the teenager received a plasma exchange and two more antiviral medication treatments — amantadine and baloxavir.

"In an accompanying editorial, experts noted while mutations were detected in her case, it’s 'unclear whether these #mutations were present in the infecting virus or emerged during the course of the patient’s illness.'

"In other words, it’s unclear if the virus #mutated to be more severe in humans.

"'The mutations evident in the Canadian case highlight the urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission,' the editorial stated, adding that vaccine development and therapeutics are also needed — perhaps to treat more severe illness. 'The Canadian case showed higher viral loads in the lower airway and very prolonged shedding, despite therapy, which highlights the potential need for longer therapy.'

"Researchers concluded their editorial with an acknowledgment that 'many questions remain.' For example, the severity of cases is likely to depend on host immunity, the route of exposure, or other changes in the virus.

"Currently, the CDC says that the risk to most Americans remains low.

"'We do have candidate vaccines and antivirals available to try to mitigate severe influenza in the case of wider spread,' the report stated. 'That said, a balance between enhanced vigilance and ‘business as usual’ is needed."

https://www.salon.com/2025/01/06/new-report-on-severe-case-of-canadian-teen-with-bird-flu/
#HPAI #BirdFluMutations #Flu

Target values for arterial CO2 in #ECMO support for #ARDS? Lower PaCO2 associated with lighter sedation:
🔍 2 independent cohorts, discovery & validation
💨 median PaCO2 41 mm Hg in both
💨 lower PaCO2 & higher pH but not HCO3 significant predictors for RASS -2 to +1 (= lightly sedated to restless); after multivariable adjustment only PaCO2 remained associated with target RASS
💨 PaCO2 ≤40 mm Hg associated with increased probability of sedation within target range in both
🖇️ https://bit.ly/45NH0vg

Prone positioning in patients with #ARDS on #ECMO support... Proning may unload & protect the RV through
🫁 homogenous lung aeration & reduced pulmonary capillary/extra-alveolar vessel compression with decreased ventral-dorsal transpulmonary pressure difference
🫁 mitigation of VILI through recruitment of collapsed alveoli in dorsal lung regions
🩸increase in thoracic circulation blood volume may recruit pulmonary microvasculature
ASAIO Journal
🖇️ https://bit.ly/4btYttI

Neue Studie im #JTH von @uniklinikum_Wue zeigt, dass #ECMO bei #ARDS zu Veränderungen in #Thrombozyten führt. Der #GPV-Rezeptor auf den #Blutplättchen wurde als mögliches Ziel zur Vermeidung von Blutungen identifiziert.
https://nachrichten.idw-online.de/2024/06/18/veraenderte-thrombozyten-unter-ecmo-erhoehen-sterberisiko-neue-ansaetze-zur-blutungspraevention

🫁 Pleural pressure & airway closure during mechanical ventilation? Some physiological considerations at the bedside...
🔓 https://rdcu.be/dKXPr
In reply to
🔓 https://rdcu.be/dKXPz

Discussion refers to editorial on esophageal pressure monitoring in #ARDS
🔓 https://rdcu.be/dKXPM

Developing AKI & after #ARDS? Individual patient-data analysis
🔍> 5K patients enrolled in 10 multicenter RCTs conducted over 20 years,
🫘incidence of AKI stable over time, overall 43.7% (from 38.8% in ARMA, to 55.8% in ROSE)
🫘 37.1% recovered rapidly from AKI; lower recovery rate in recent trials
🪦 90-day excess in mortality attributable to AKI 15.4% (decreasing from ARMA to FACTT then stable over time: AKI remains significant contributing factor to mortality.
🖇️ http://bit.ly/3XiMqfq

Prolonged VV #ECMO for #ARDS in adults, analysis of ELSO - Extracorporeal Life Support Organization Registry:
🔍 >13 K patients included, 2012-2022
⏳ prolonged #extracorporeal support increased & accounts for substantial portion of cases
🫁 among pts that survive for at least 21 days, run duration is not predictive of survival to hospital discharge
Subjectively withdrawing care due to run duration should be reconsidered.
🔓 https://bit.ly/4aYCACt

With editorial
🔓 https://bit.ly/3VhWhQ7

Finding optimal tidal volume in #ARDS
🫁 is ΔP indicator of unsafe VT & does it directly impact on outcome?
🫁 what factors can influence CRS + interplay between VT & ΔP?
We should continue using protective mechanical ventilation but, rather than fixed cut-of (6 ml/kg PBW) it may be more advantageous individualize VT considering multifactorial contribution of ∆P, CRS, ECW, PEEP + regional lung mechanics.
Free to read #FOAMcc on @ICM
🔓 https://rdcu.be/dHUzd

Predicting #ECLS survival? External validation of PRESET - PREdiction of Survival on Extracorporeal Membrane Oxygenation Therapy - score:
🔍 single 🇩🇪 center study including 283 patients with #ARDS, various etiology, undergoing VV #ECMO (2012-2022)
🪦 in-hospital mortality 50.88%
⚖️ median severity scores SAPS-II 38, SOFA 12, PRESET 7
🔍 SAPS-II displayed best prognostic value; prediction performance weak in all analyzed scores despite good calibration
ASAIO Journal
🖇️ https://bit.ly/3UV6aEe

#ARDS guidelines, ESICM vs ATS??
🌊 Both reached similar conclusions. emphasizing challenges in issuing blanket recommendations that apply to all patients + importance of individualising patient care.
🔓 https://rdcu.be/dHb9X
🚇 Mind gap! Underscores need for collaboration/dialogue between scientific societies to develop synergistic clinical (living) guidelines.
🔓 https://rdcu.be/dHcav
🫁 Guidelines can be useful in certain situations, but should not replace reasoning!
🔓 https://rdcu.be/dHb8e

⏱️ #ARDS? first 24 h should be time stamped:
1️⃣ 🔍 first 3h of non-invasive/invasive respiratory support: rule in diagnosis
2️⃣ ⚖️ first 12h: decide to continue NIV or institute IMV
3️⃣ 🫁 first 6h: implement low Vt strategies & optimization based on Pplat & DP
4️⃣ 🫁 first 12h: Initiate/optimize PEEP
5️⃣ 🛌 first 12-24h: prone eligible pts
6️⃣ 🩸 first 3-6h: #ECLS in patients meeting EOLIA criteria, depending on severity + response to previous interventions + risk/benefit profile
🔓 https://rdcu.be/dGXCI

Prone positioning on #ECMO for severe #ARDS??
🚦PRO: Performed in experienced/highly specialized centers, PP feasible/safe promising option
🔓 https://rdcu.be/dGIMf
🚦CON: according to PRONECMO trial results, PP during #ECLS did not yield significant benefits vs supine position.
🔓 https://rdcu.be/dGILB
🚦NOT SURE: How to reconcile the results of high-quality, negative RCT with preexisting favorable observational data?
🔓 https://rdcu.be/dGINm
All free to read #FOAMcc #FOAMecmo on @ICM

🧠 🫁 Mitigating/managing cerebral complications of #ARDS?? Clinical decision making must integrate neuromonitoring-guided evaluation & selection of lung protective interventions with consideration of individual patient cerebral physiology. Individualized approach could prevent additional brain injury, improving neurological outcomes in survivors, potentially impact on post-intensive care syndrome outcomes.
Free to read #FOAMcc on @ICM
🔓 https://bit.ly/4djO8mh

Safe ventilation in #ARDS?? Elusive... justifying use of #ECLS. Challenge is to treat lung disease effectively while mitigating injury risks. Free to read #FOAMcc on @ICM
🔓 https://rdcu.be/dGq5p

In reply to
🔓 https://rdcu.be/dGq6n

All refers to editorial on VILI
🔓https://rdcu.be/dGq6G

Prone positioning?? Used since 70s to improve oxygenation in patients with #ARDS. Beyond oxygenation benefits, it plays crucial role in preventing VILI + in preserving/improving
hemodynamics, leading to reduced mortality in selected patients. Here concise overview:
🫁 main pathophysiological findings
🫁 supporting evidence & practical considerations for use
🫁 awake proning in non-intubated patients
Free to read #FOAMcc on Intensive Care Medicine
🔓 https://rdcu.be/dFIdO

Lung ultrasound in #ARDS
🖥️ LUS examination in ARDS
🖥️ diagnosis
🖥️ management
LUS essential for diagnosing & managing ARDS due bedside accessibility/availability across different resource settings, aiding in diagnosis & monitoring of ARDS progression + treatment response, while also offering potential for subphenotyping. #POCUS #echofirst
🎥 PS check supplementary videos!!
🖇️ https://bit.ly/49VMTXw

Optimizing PEEP in #ARDS, physiological evidence, bedside strategies & clinical applications:
❓ why do we apply PEEP?
🫁 definition of lung recruitability
🔍 what does the evidence say about PEEP setting?
🫁 practical & pragmatic approach
⚙️ advanced methods
No one among available options for tailoring PEEP proved to be superior to others... so clinical practice is highly variable; integration into clinical settings may be challenging.
Free to read #FOAMcc on @ICM
🔓 https://rdcu.be/dDFbN