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03:37

Deleted Account

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Midnight Rider Channel 🇺🇸 21.09.2021 14:29:57

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I just caught the end of President Trump on Glen Beck talking about Milley- “bad things should happen to him”

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03:38

Patty212

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Patriot Streetfighter 20.09.2021 17:08:49


03:38

Deleted Account

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Midnight Rider Channel 🇺🇸 21.09.2021 14:09:14

https://www.dailymail.co.uk/sciencetech/article-10008567/Google-sends-broadband-Congo-River-beams-light.html

03:40

Deleted Account

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THOUGHTS 19.09.2021 22:58:16


THOUGHTS

https://t.me/myheartbelongstohim

MH

03:42

Matt Hosner

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03:42

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Midnight Rider Channel 🇺🇸 22.09.2021 03:00:55

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What!

03:45

Deleted Account

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David Avocado Wolfe 02.08.2021 21:16:01

Summary of the Spike Protein and Graphene Oxide Detoxification Protocol


http://bit.ly/SpikeProtein


This is the updated Nutrition protocol to protect those who’ve been injected with spike protein, graphene oxide and mRNA and the same protocol is useful to protect those concerned with the spike protein and graphene oxide shedding coming off those who’ve been injected. We now have evidence of the latest injections containing: mRNA, spike protein, graphene oxide, SM-102, and numerous other potentially toxic substances (also: some—but not all—injections, appear to be higher in graphene oxide and some appear to be saline placebos).


If you know someone who has been injected and requires help, please provide them with this Nutrition Protocol:


Most Important Elements of the Protocol (Shortlist Summary)


Spike Protein: Shikimate neutralizes the S.pike Protein


Shikimate Main Sources to Detox S.pike Protein

• Pine Needle Tea for shikimic acid or shikimate (from green edible pine needles) There are toxic pine needles, be careful! When drinking pine needle tea, drink the oil/resin that accumulates too!

And/Or

• Fennel and/or Star Anise Tea

And/Or

• Schizandra Berry Tea


• Iodine* (dosage depends on brand, more is not better). Iodine is a product you have to start with small dosages and build up over time.


• Vitamin D3* (10,000 IU’s per day)


Graph.ene Oxide Detox:


• C60 (1-3 droppersfull per day): One of the issues we are seeing with those who have been injected is disturbances in their energetic field (magnetism) and hot spots of inflammation. C60 is a rich-source of electrons and acts like a fire extinguisher to inflammation and simultaneously (because it bio-distributes throughout the body) drives a normalization of electron flow throughout the body. In this category, we offer two products, the traditional C60 product* is made by yours truly and the C60 SuperConcentrate* is made by a carbon scientist friend of mine and contains a higher concentration of electrons. C60 is recommended to neutralize s.pike protein, detoxify graphene oxide and SM-102.


• Kohlbitr Activated Charcoal: Take between 400-2000mg (1-5 capsules) a day with water.


• NAC: N-Acetyl Cystiene is the best precursor to glutathione in the body which has the best research for neutralizing graphene oxide. Take 900-1800 mg a day. Get it while you can. The US Federal communist government is trying to make NAC illegal unless you have a doctor’s prescription.


• Enzymes (especially those containing serrapeptase and nattokinase such as VeganZyme— dosage for VeganZymes is 3 caps, twice daily):

Serrapeptase: Serrapeptase provides the anti-inflammatory breakdown of excess and unusual protein. Dosage: 100-200 mg on an empty stomach per day.

Nattokinase: Nattokinase has a long history of being used to prevent blood clots. 2000-4000 Fibrinolytic Units per day (2-4 capsules) with or without food.


Special Note: Iver.mectin is showing great promise against hydrogels containing graphene oxide and found on PCR test swabs, but it is a pharmaceutical, so I do not include it.


Here is the Complete Protocol


•Coated Silver (1-6 drops per day, depending on degree of exposure) (Coated silver blocks the sulfur-bearing protein on the spikes from entering the cell. Sulfur-rich amino acids on the spike protein interact with silver causing them to fold incorrectly).

• NAC (N-acetyl cysteine) (accelerates detoxification and is considered a producer of the super detoxifier glutathione in the body) Dosage: 1200-2400 mg per day on an empty stomach. NAC is recommended to detoxify graphene oxide and SM-102. NAC is tough to find after the FDA recently made it illegal to purchase over the counter in the USA. Request NAC from your doctor!

• Zinc (30-80mg per day depending on immunological pressure)

• Vitamin D3* (10,000 IU’s per day)

• Lyposomal Vitamin C (30ml, twice daily)*

• Quercetin (500-1000 mg, twice daily)*

• Iodine* (dosage depends on brand, more is not better). Iodine is a product you have to start with small dosages and build up over time.

• PQQ* (20-40 mg per day)

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03:45

Patty212

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KanekoaTheGreat 21.09.2021 17:22:16

Sidelined? Hundreds of Navy SEALS told they won't be deployed if they refuse COVID vaccine


Several hundred elite Navy SEALs are in danger of being blocked from deploying with their special operator teams by the Pentagon after failing to get a mandatory COVID vaccine.


The number involved in the dispute with the Pentagon amounts to as many as a quarter or more of all active duty SEALs, a loss that could impact military readiness since SEAL teams play an outsized role in modern military operations.


"If they continue to with this asinine police you are going to have the complete decimation of the SEAL teams."


The SEALS are not anti-vaccine; in fact they get all sorts of shots. They just believe more safety data needs to be be available to make their own judgment. And some already have immunity from surviving the disease.


Who would have thought that China Joe's policies would wipe out our SEAL teams❓


https://justthenews.com/government/security/hundreds-navy-seals-face-being-blocked-deployment-refusing-covid-vaccine


@KanekoaTheGreat

03:46

Deleted Account

M

Midnight Rider Channel 🇺🇸 22.09.2021 01:21:49

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Biden’s Birder is in purpose

03:46

Deleted Account

M

Midnight Rider Channel 🇺🇸 22.09.2021 01:21:59

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Steven Miller - If someone doesn’t hold this presidency accountable there won’t be a country

03:46

Deleted Account

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David Avocado Wolfe 02.08.2021 21:16:01

Shikimate Main Sources:

• Pine Needle Tea for shikimic acid or shikimate (from green edible pine needles) There are toxic pine needles, be careful! When drinking pine needle tea, drink the oil/resin that accumulates too! Shikimate, shikimic acid and their derivatives possess: cancer fighting, antiviral, antimicrobial, anticoagulant and antithrombotic properties.

• Fennel and/or Star Anise Tea: These are also an excellent source of shikimate or shikimic acid (which is known to neutralize the spike protein)

• Schizandra Tea: Ranked in the top three of all superherbs on Earth. Schizandra berries are rich in shikimate amongst numerous extraordinary other properties.


• C60 (1-3 droppersfull per day): One of the issues we are seeing with those who have been injected is disturbances in their energetic field (magnetism) and hot spots of inflammation. C60 is a rich-source of electrons and acts like a fire extinguisher to inflammation and simultaneously (because it bio-distributes throughout the body) drives a normalization of electron flow throughout the body. In this category, we offer two products, the traditional C60 product* is made by yours truly and the C60 SuperConcentrate* is made by a carbon scientist friend of mine and contains a higher concentration of electrons. C60 is recommended to neutralize s.pike protein, detoxify graphene oxide and SM-102.


• Charcoal (2-4 capsules a day): Charcoal is the pre-eminent detoxifier and when taken on an empty stomach, works its way down into the intestines and activates a blood purification process known as “interstitial dialysis”. Our Kohlbitr* product is the premier activated coconut charcoal in the world and we also now offer the more gentle birch charcoal.*


Hesperidin sources to help disable s.pike protein:

• Citrus fruit (especially blood oranges, due to their high hesperidin content — hesperidin is a chalcone like quercetin that deactivates spike protein)

• Peppermint (very high in hesperidin)


Superherbs to help disable s.pike protein:

• Triphala formulations: In Sanskrit, the word Triphala means "three fruits”: a combination of Indian gooseberry (Emblica officinalis), black myrobalan (Terminalia chebula) and belleric myrobalan (Terminalia belerica). The terminalia fruits are rich in shikimate.

• St. John’s Wort (shikimate is found throughout the entire plant and in the flowers)

• Comfrey Leaf (rich in shikimate)

• Feverfew (leaves and flowers are rich in shikimate)

• Gingko Biloba Leaf (rich in shikimate)

• GiantHyssop or Horsemint (Agastache urtifolia) (rich in shikimate)

• LiquidAmbar (Sweet Gum tree) A tea of the spiky seed pods is rich in shikimate.

•Glycyrrhiza glabra (Chinese medicine’s licorice root): Glycyrrhizic acid is extracted from the root of the licorice plant inhibits spike protein. https://pubmed.ncbi.nlm.nih.gov/33041173/


Foods

• Carrots and Carrot Juice (rich in Shikimate)

• Dandelion Leaf (Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro)


Plant Sprouts

• Wheatgrass and Wheatgrass Juice (the young blades are high in shikimate)

• Legume family beans that are generally considered to be rich in shikimate. I have found testing of 5 sprouts and all were rich in shikimate: red kidney bean (Phaseolus vulgaris), moth bean (Vigna aconitifolia), soy bean (Glycine max), mung bean (Vigna radiata) and alfalfa (Medicago saliva). All these were analysed for their shikimic acid content during germination: so the sprouting process is key to activate shikimate production.


 


https://instagram.com/mikepompeo86


Unofficial

https://t.me/MichaelRPompeo

03:23

Deleted Account

M

Midnight Rider Channel 🇺🇸 21.09.2021 19:39:19

https://www.dailymail.co.uk/health/article-10013497/Scientists-working-develop-plants-deliver-mRNA-vaccine-technology.html

MH

03:23

Matt Hosner

Mike Lindell

Inventor and CEO of MyPillow, Author of "What Are the Odds? From Crack Addict to CEO,” Executive Producer, Creator of MyStore and Lindell Recovery Network

https://t.me/MichaelJLindell

MH

03:24

Matt Hosner

ℚ𝕦𝕖𝕤𝕥𝕚𝕠𝕟 𝔼𝕧𝕖𝕣𝕪𝕥𝕙𝕚𝕟𝕘 21.09.2021 23:21:25

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School in Chester, England is served liability papers for their role in facilitating child experimental vaccinations.


This process needs to happen in every school that is allowinr experimentation on their pupils.

MH

03:24

Matt Hosner

🐸 We The Pepe 🐸

🐸 We bake🐸

🐸WWG1WGA🐸

https://t.me/qanonofficial

MH

03:26

Matt Hosner

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Right Side Broadcasting Network (RSBN) 21.09.2021 01:20:35


Statement by Donald J. Trump, 45th President of the United States of America

MH

03:27

Matt Hosner

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John Durham 20.09.2021 19:32:42

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I'm here.


Join @Real_JohnDurham

MH

03:27

Matt Hosner

John Durham

Special Counsel for the United States Department of Justice

https://t.me/Real_JohnDurham

Deleted invited Deleted Account

03:29

Deleted Account

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Midnight Rider Channel 🇺🇸 21.09.2021 17:50:13

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03:31

Matt Hosner

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The Storm 22.09.2021 03:26:58

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RFK JR speaks truth #FightBack


Follow @FreeSpeechParty 🇺🇸🦅


Our store: FreeSpeechParty.store 👕

MH

03:31

Matt Hosner

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World Awakening 22.09.2021 02:20:10

​​A court hearing was held this morning in Georgia regarding the verification of absentee ballots of Fulton County.


Judge Brian Amero gave the State Election Commission and the GBI (Georgia Bureau of Investigation) 20 days to explain to the court what was done to investigate the appearance of fake ballots in Fulton County, Georgia, after defense attorneys said that an investigation of fake ballots was already underway.


Judge Amero then ended the hearing. They will meet again in 20 days.


On Monday evening, VoterGA co-founder Garland Favorito issued a statement about today's hearing.

VoterGA believes that today's hearing confirmed their previous conclusions.


"Today, the court confirmed several things that we have been saying all the time:


There is evidence of election fraud in the affidavits of senior poll managers who swear that they processed fake ballots during a manual counting check in Fulton County.


The applicants ' claims for equal protection and due process of law are well-founded allegations of violations of constitutional rights based on evidence.


It is necessary to check the ballots to determine whether they are fake and whether the constitutional rights of the petitioners have been violated.


@WorldawakeningTrueNews

MH

03:32

Matt Hosner

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Wakey wakey 21.09.2021 20:32:54


Here is the set up for perpetual boosters for years to come......


Pfizer and Moderna say COVID-19 vaccine protection wanes after six to eight months

↙️⬇️↘️

https://nationalpost.com/health/pfizer-and-moderna-say-covid-19-vaccine-protection-wanes-after-six-to-eight-months/wcm/6511eadb-7871-443f-9b8f-0d427e301715/



However they are not talking about the fact that natural immunity is best. With waning vaccine immunity, natural immunity is king.

Why are governments forcing recovered individuals to take the vaccine?


The Pfizer COVID vaccine "protects" against severe disease and death for at least 6 months, while protection against asymptomatic and symptomatic infections wanes rapidly.


They believe that now. COVID is seasonal and endemic. It will ramp up in the northeast in the coming months, regardless of vaccinations.


As soon as the weather gets colder and people with low vitamin D go inside, it’s gonna get really bad up here in the north.

03:32

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Wakey wakey 21.09.2021 20:32:54


03:32

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Wakey wakey 21.09.2021 20:32:54


03:32

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Wakey wakey 21.09.2021 20:32:54

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03:32

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Wakey wakey 21.09.2021 20:32:55


03:32

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Wakey wakey 21.09.2021 20:32:55

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03:33

Deleted Account

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Midnight Rider Channel 🇺🇸 21.09.2021 16:44:05

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MH

03:34

Matt Hosner

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GhostEzra 21.09.2021 21:54:51

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Arrest of a doctor prescribing ivermectin.

03:35

Deleted Account

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Digital Nukes 22.09.2021 01:46:04

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@DigitalNukes ☢️

03:35

Deleted Account

M

Midnight Rider Channel 🇺🇸 21.09.2021 16:02:13


 WW3 Digital Soldiers 🌍

Previous messages

22 September 2021

MH

03:17

Matt Hosner

The Meitryx

It's me, Lisa Mei Crowley. I will post & share newsworthy items I come across on this channel. It's basically going to be a news feed. I'm intentionally keeping comments turned off to prevent bad actors from posting porn or calls for violence on my feed.

https://t.me/themeitryx

03:17

Deleted Account

M

Midnight Rider Channel 🇺🇸 21.09.2021 21:55:27

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00:49, 6.3 MB

MH

03:18

Matt Hosner

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Wendy Rogers 22.09.2021 03:16:28

IT ONLY TAKES TIRELESS IRATE MINORITY TO KEEP THE REPUBLIC ALIVE

MH

03:19

Matt Hosner

Plastic Girl Reporting™️

Made In America

God Fearing Patriot

Freedom Fighter

Defender of the Constitution

Join the commentary:


Main https://t.me/plasticgirlreport

Chat https://t.me/plasticgirlreportin


🇺🇸🦅🗽⚖️🔔🪖🛡⚔️🙏🏼✝️🇺🇸

https://t.me/plasticgirlreport

MH

03:19

Matt Hosner

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Red Pill Truth 22.09.2021 03:15:01

https://www.zerohedge.com/political/there-real-risk-government-will-shutdown-end-month


@RedPillPharmacy 💊

MH

03:19

Matt Hosner

Red Pill Pharmacy

Filling your daily dose of Red Pills!


AmericanSwitchProject.com

https://t.me/RedPillPharmacy

MH

03:19

Matt Hosner

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General Flynn ️ 22.09.2021 03:14:30

https://rumble.com/vmsi2v-general-flynn-fireside-chat-2-why-its-not-okay-to-say-i-was-just-following-.html

MH

03:19

Matt Hosner

@RealGenFlynn

This is the real General Michael T. Flynn TGS page. I mainly post on Clouthub @GenFlynn

https://t.me/RealGenFlynn

MH

03:20

Matt Hosner

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Ron Watkins [CodeMonkeyZ] 22.09.2021 03:12:40

https://rumble.com/vmsku4-leaked-audio-maricopa-county-supervisor-thinks-ballot-harvesting-and-dead-v.html

MH

03:20

Matt Hosner

CodeMonkeyZ [Ron Watkins]

Ron Watkins [ gab.com/codemonkey ]

https://t.me/CodeMonkeyZ

Julie invited Julie

MH

03:20

Matt Hosner

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Midnight Rider Channel 🇺🇸 22.09.2021 02:10:29

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So the debt ceiling was established in 1917- Herman is calling it a Pond of piranhas in your backyard next to the swing set and it’s ridiculous to still have it - I just can’t get out of my head that President Trump kept bringing up the flu of 1917 instead of saying 1916 coincidence?

MH

03:21

Matt Hosner

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Donald Trump (Official) 21.09.2021 23:15:03


If You Know You Know😉

MH

03:21

Matt Hosner

D

Donald Trump (Official) 22.09.2021 01:56:01

Psalm 20:4


May he grant you your heart's desire and fulfill all your plans!

MH

03:21

Matt Hosner

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Diamond and Silk 22.09.2021 00:16:16

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🛑 BOOOOM 🛑


BANNED VIDEO - VACCINE LIES EXPOSED - CRIMES AGAINST HUMANITY! - THOUGHTS?


SHARE IT! SHARE EVERYWHERE!


Join👇👇👇

@DiamondandSilkOfficial

MH

03:21

Matt Hosner

UntamedTruth (Official)

A dedicated focus on protecting our children and future generations from lies, deception, false narratives, and suppressed/censored information. Expect numerous feeds per day and a wide variety of topics.

https://t.me/UntamedTruth

MH

03:22

Matt Hosner

KV

Kat Van 21.09.2021 06:45:53


MH

03:22

Matt Hosner

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The Trump Era 47 22.09.2021 00:45:06

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General Flynn says that the Democrat Party no longer exists.


It’s now two groups:


A). Conservatives/Patriots

B). Socialists/Communists


I think we all know which side is going to win this fight.

MH

03:23

Matt Hosner

Q17 - The Storm Is Upon Us

It's time to WAKE up !


Q17 - The Storm Is Upon Us

https://t.me/Q17_TheStorm

MH

03:23

Matt Hosner

M

Mike Pompeo 22.09.2021 00:13:25

President Biden was right in saying the world sits at a critical moment and that the world needs strong American leadership.


Unfortunately, that leadership was nowhere to be found during President Biden’s address.

https://www.foxnews.com/opinion/un-biden-world-stage-mike-pompeo


👇👇👇

@MichaelRPompeo

MH

03:23

Matt Hosner

Mike Pompeo

Former U.S. Secretary of State, Director of the CIA, Congressman. Christian, husband, father, Army veteran, Kansan and proud American 🇺🇸


 


ABSTRACT


This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.


PMID:37844585 | PMC:PMC10586005 | DOI:10.1177/10760296231206799

00:04

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Treatment Evolution: A Comparative Analysis of Pulmonary Embolism Response Team Management at a Single Institution


Am J Cardiol. 2023 Oct 14;208:171-172. doi: 10.1016/j.amjcard.2023.09.003. Online ahead of print.


NO ABSTRACT


PMID:37844520 | DOI:10.1016/j.amjcard.2023.09.003

00:04

PubMed articles on: Cancer & VTE/PE

Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study


J Thromb Thrombolysis. 2023 Oct 15. doi: 10.1007/s11239-023-02903-w. Online ahead of print.


ABSTRACT


Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q test, "Leave-one-out," and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998-1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, - 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE. Causal effect of atrial fibrillation on pulmonary embolism: a Mendelian randomization study. AF atrial fibrillation, PE pulmonary embolism, GWAS genome-wide association studies, SNPs single nucleotide polymorphisms, OR odds ratio, CI confidence interval.


PMID:37839022 | DOI:10.1007/s11239-023-02903-w

00:04

PubMed articles on: Cancer & VTE/PE

Concomitant Cerebral Venous Thrombosis and Intracranial Hemorrhages in Presentation of a Patient with Secondary Polycythemia: A Case Report


Am J Case Rep. 2023 Oct 15;24:e941507. doi: 10.12659/AJCR.941507.


ABSTRACT


BACKGROUND Cerebral ischemia and hemorrhages were reported to be the main complications of polycythemia vera (PV). The relationship between PV and increased risk of the cerebrovascular events has been established. Some patients with secondary polycythemia have thromboembolic events comparable to those of PV. However, secondary polycythemia that leads to cerebrovascular events is uncommon. CASE REPORT A 35-year-old man without any prior medical history presented with mild clinical acute ischemic stroke and polycythemia. The patient then showed worsening neurological deficits that were later attributed to the concurrent cerebral venous thrombosis, which led to malignant cerebral infarction with hemorrhagic transformation, and subarachnoid hemorrhage. His polycythemia appeared to be secondary to bacterial infection. The treatments for the secondary polycythemia were first phlebotomy and intravenous hydration, followed by intravenous broad-spectrum antibiotics. PV was excluded because the JAK2 V617F mutation was absent, the patient's peripheral blood smear suggested secondary polycythemia due to bacterial infection, and there were improvements in hemoglobin, erythrocyte count, and hematocrit after intravenous antibiotics. At the 1-month follow-up, he was moderately dependent, and hemoglobin, erythrocyte count, and hematocrit were within normal limits, without receiving any further phlebotomy or cytoreductive agents. CONCLUSIONS This case highlights the plausible causation of secondary polycythemia that could lead to concomitant cerebral thrombosis and hemorrhagic events. The diagnosis of cerebral venous thrombosis should be considered in a patient who presents with headache, focal neurological deficits, polycythemia, and normal head computed tomography scan.


PMID:37838828 | PMC:PMC10584197 | DOI:10.12659/AJCR.941507

 


ABSTRACT


Non-bacterial thrombotic endocarditis (NBTE) involves the deposition of fibrin and platelets on heart valves, frequently leading to systemic embolism. The association between NBTE and cancer demands thorough investigation in cases lacking an evident cause. This case report elucidates the clinical course of a nonsmoking woman in her sixties with NBTE linked to pulmonary adenocarcinoma. The patient, who had a history of multiple sclerosis (MS) and was receiving dimethyl fumarate treatment, presented to the emergency department with stroke-like symptoms. Diagnostic challenges arose due to preexisting motor sensory impairment from MS. Initial evaluations revealed hypocapnia and elevated inflammatory markers. Blood cultures were obtained twice, and imaging confirmed pneumonia, left pleural effusion, and chronic pulmonary embolism while excluding acute vascular events or intracranial hemorrhage. The first transthoracic echocardiogram (TTE) indicated no cardiac abnormalities. Treatment encompassed parenteral antibiotics, systemic anticoagulation, and admission to medical floors. Although the initial treatment yielded a positive clinical response, subsequent complications emerged. On the tenth day, the patient required additional interventions, including broad-spectrum antibiotics and supplemental oxygen. A follow-up chest X-ray revealed persistent pneumonia and pleural effusion, and blood cultures upon admission returned negative. A subsequent head MRI confirmed an embolic stroke and displayed evidence of MS progression. Around the twentieth day, empirical treatment for infective endocarditis was initiated, and an 8 mm vegetation on the aortic valve was identified via transesophageal echocardiography (TOE). Acute pulmonary edema prompted a transfer to the intermediate care unit. Further investigations, including left thoracocentesis and CT, unveiled exudate and metastatic lesions in the liver, ilium, and kidney. Unfortunately, on the twenty-fifth day, the patient experienced acute myocardial infarction, right leg ischemia, disseminated intravascular coagulation, and shock. Pleural fluid analysis revealed malignant cells suggestive of lung adenocarcinoma. This case underscores the pivotal role of timely NBTE recognition and the search for malignancy when workup for infective endocarditis and autoimmune panels is negative. Moreover, it emphasizes the significance of vigilant monitoring, particularly in immunocompromised individuals or those with preexisting neurological deficits, especially when new neurological symptoms manifest. These insights significantly contribute to the comprehension of NBTE management and its implications for analogous patient cohorts.


PMID:37846253 | PMC:PMC10576842 | DOI:10.7759/cureus.45271

00:04

PubMed articles on: Cancer & VTE/PE

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism


Res Synth Methods. 2023 Oct 17. doi: 10.1002/jrsm.1676. Online ahead of print.


ABSTRACT


The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.


PMID:37846195 | DOI:10.1002/jrsm.1676

00:04

PubMed articles on: Cancer & VTE/PE

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis


Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231206799. doi: 10.1177/10760296231206799.


 


ABSTRACT


BACKGROUND: Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking.


OBJECTIVES: We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment.


PATIENTS/METHODS: Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study.


RESULTS: In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]).


CONCLUSIONS: Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.


PMID:37852838 | DOI:10.1016/j.ejim.2023.10.014

00:04

PubMed articles on: Cardio-Oncology

The (pro)renin Receptor - A Regulatory Nodal Point in Disease Networks


Curr Drug Targets. 2023 Oct 25. doi: 10.2174/0113894501250617231016052930. Online ahead of print.


ABSTRACT


Experimental inhibition of the (pro)renin receptor [(P)RR] is a promising therapeutic strategy in different disease models ranging from cardiorenal to oncological entities. Here, we briefly review the direct protein-protein interaction partners of the (P)RR and the plethora of distinct diseases in which the (P)RR is involved. The first structural work on the (P)RR using AlphaFold, which was recently published by Ebihara et al., is the center of this mini-review since it can mechanistically link the protein-protein interaction level with the pathophysiological level. More detailed insights into the 3D structure of the (P)RR and its interaction domains might guide drug discovery on this novel target. Finally, antibody- and small molecule-based approaches to inhibit the (P)RR are shortly discussed.


PMID:37885110 | DOI:10.2174/0113894501250617231016052930

00:04

PubMed articles on: Cancer & VTE/PE

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign


Cureus. 2023 Sep 14;15(9):e45271. doi: 10.7759/cureus.45271. eCollection 2023 Sep.


 



ABSTRACT


Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100 K/μL at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio (SHR) 2.4, P=0.02) and CRNMB (17.9% vs. 9.6%, SHR 2.0, P=0.01). Thrombocytopenia did not impact recurrent VTE (9.8% vs. 7.4%, SHR 1.3, P=0.37) nor overall mortality (21.8% vs. 26.0%, HR 0.9, P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs 0, p.


PMID:37855029 | DOI:10.3324/haematol.2023.284192

00:04

PubMed articles on: Cardio-Oncology

Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity


Iran J Basic Med Sci. 2023;26(11):1298-1304. doi: 10.22038/IJBMS.2023.70997.15422.


ABSTRACT


OBJECTIVES: Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity.


MATERIALS AND METHODS: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured.


RESULTS: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB.


CONCLUSION: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.


PMID:37885998 | PMC:PMC10598814 | DOI:10.22038/IJBMS.2023.70997.15422

00:04

PubMed articles on: Cancer & VTE/PE

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study


Eur J Intern Med. 2023 Oct 16:S0953-6205(23)00369-2. doi: 10.1016/j.ejim.2023.10.014. Online ahead of print.


 


ABSTRACT


Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient's cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases.


PMID:37886969 | PMC:PMC10605822 | DOI:10.3390/cimb45100526

00:04

PubMed articles on: Cancer & VTE/PE

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies


Thromb Res. 2023 Oct 11;231:128-134. doi: 10.1016/j.thromres.2023.10.004. Online ahead of print.


ABSTRACT


BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear.


METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk.


RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs.


CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.


PMID:37857226 | DOI:10.1016/j.thromres.2023.10.004

00:04

PubMed articles on: Cardio-Oncology

Retraction: Longitude variation of the microRNA-497/FGF-23 axis during treatment and its linkage with neoadjuvant/adjuvant trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients


Front Surg. 2023 Oct 11;10:1307330. doi: 10.3389/fsurg.2023.1307330. eCollection 2023.


ABSTRACT


[This retracts the article DOI: 10.3389/fsurg.2022.862617.].


PMID:37886634 | PMC:PMC10599136 | DOI:10.3389/fsurg.2023.1307330

00:04

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism


JACC Cardiovasc Interv. 2023 Sep 27:S1936-8798(23)01212-8. doi: 10.1016/j.jcin.2023.08.029. Online ahead of print.


NO ABSTRACT


PMID:37855803 | DOI:10.1016/j.jcin.2023.08.029

00:04

PubMed articles on: Cancer & VTE/PE

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer


Haematologica. 2023 Oct 19:0. doi: 10.3324/haematol.2023.284192. Online ahead of print.

 



ABSTRACT


Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab-pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.


PMID:37887554 | PMC:PMC10605836 | DOI:10.3390/curroncol30100654

00:04

PubMed articles on: Cardio-Oncology

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine


Curr Issues Mol Biol. 2023 Oct 15;45(10):8337-8358. doi: 10.3390/cimb45100526.


 


ABSTRACT


Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.


PMID:37889193 | DOI:10.1161/JAHA.123.029574

00:04

PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban


Front Pharmacol. 2023 Oct 4;14:1263975. doi: 10.3389/fphar.2023.1263975. eCollection 2023.


ABSTRACT


Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.


PMID:37860116 | PMC:PMC10582335 | DOI:10.3389/fphar.2023.1263975

00:04

PubMed articles on: Cardio-Oncology

Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy


Curr Oncol. 2023 Oct 6;30(10):9049-9062. doi: 10.3390/curroncol30100654.

 



ABSTRACT


Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.


PMID:37889357 | DOI:10.1007/s10565-023-09835-4

00:03

PubMed articles on: Cancer & VTE/PE

Clinical Care of Pediatric Patients with or At-Risk of Post-Thrombotic Syndrome: Guidance from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Haemostasis


J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00780-8. doi: 10.1016/j.jtha.2023.10.012. Online ahead of print.


NO ABSTRACT


PMID:37866514 | DOI:10.1016/j.jtha.2023.10.012

00:03

PubMed articles on: Cancer & VTE/PE

Catheter Directed Thrombectomy and Other Deep Venous Interventions in Cancer Patients


Tech Vasc Interv Radiol. 2023 Jun;26(2):100900. doi: 10.1016/j.tvir.2023.100900. Epub 2023 Aug 5.


ABSTRACT


Treating cancer patients with deep venous thrombosis/venous thromboembolism (DVT/VTE) can be challenging as patients are frequently unable to receive the standard therapy of anticoagulation due to the increased risk of bleeding complications seen in this population. Similarly, the hesitation of interventionalists to use thrombolytic agents due to bleeding risks limits percutaneous intervention options as well. Further, outcome data and guidelines do not exist for oncologic patients and often treatment is tailored to patient-specific factors after multidisciplinary discussion. This article reviews specific factors to consider when planning percutaneous treatment of cancer patients with DVT/VTE, focusing on the iliocaval system.


PMID:37865450 | DOI:10.1016/j.tvir.2023.100900

00:04

PubMed articles on: Cardio-Oncology

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study


J Cardiovasc Dev Dis. 2023 Oct 4;10(10):418. doi: 10.3390/jcdd10100418.


ABSTRACT


1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.


PMID:37887865 | PMC:PMC10607871 | DOI:10.3390/jcdd10100418

00:04

PubMed articles on: Cardio-Oncology

Circulating Cardiovascular Biomarkers in Cancer Therapeutics-Related Cardiotoxicity: Review of Critical Challenges, Solutions, and Future Directions


J Am Heart Assoc. 2023 Oct 27:e029574. doi: 10.1161/JAHA.123.029574. Online ahead of print.


 


ABSTRACT


BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.


OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.


METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.


RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants.


DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.


PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

00:03

PubMed articles on: Cardio-Oncology

Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity


Cell Biol Toxicol. 2023 Oct 27. doi: 10.1007/s10565-023-09835-4. Online ahead of print.

 


ABSTRACT


Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.


PMID:37890547 | DOI:10.1016/j.ahj.2023.10.007

00:03

PubMed articles on: Cancer & VTE/PE

Comparison of Direct Oral Anticoagulants versus Low Molecular Weight Heparin in Primary and Metastatic Brain Cancers: A Meta-Analysis and Systematic Review


J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.


 


ABSTRACT


BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.


PMID:37872733 | DOI:10.12659/AJCR.941360

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PubMed articles on: Cardio-Oncology

Cardiovascular Impact of Near Complete Estrogen Deprivation in Premenopausal Women with Breast Cancer: The CROWN Study


Am Heart J. 2023 Oct 25:S0002-8703(23)00300-9. doi: 10.1016/j.ahj.2023.10.007. Online ahead of print.


 



ABSTRACT


D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), to evaluate the risk of VTE recurrence as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, spanning from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals presenting with increased Ddimer without signs or symptoms of thrombus formation. To the management of these cases by the hematologist is dedicated this narrative review.


PMID:37881856 | DOI:10.3324/haematol.2023.283966

00:03

PubMed articles on: Cancer & VTE/PE

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury


Am J Case Rep. 2023 Oct 24;24:e941360. doi: 10.12659/AJCR.941360.


 


ABSTRACT


Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.


PMID:37890926 | DOI:10.1016/bs.mcb.2023.02.014

00:03

PubMed articles on: Cancer & VTE/PE

How we manage a high D-dimer


Haematologica. 2023 Oct 26. doi: 10.3324/haematol.2023.283966. Online ahead of print.


 


ABSTRACT


BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE).


METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database.


RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs).


CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.


PMID:37882319 | DOI:10.1002/cam4.6626

00:03

PubMed articles on: Cardio-Oncology

Simplified rules-based tool to facilitate the application of up-to-date management recommendations in cardio-oncology


Cardiooncology. 2023 Oct 27;9(1):37. doi: 10.1186/s40959-023-00179-w.


ABSTRACT


BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated.


METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions.


RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples.


CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors.


TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.


PMID:37891699 | PMC:PMC10605976 | DOI:10.1186/s40959-023-00179-w

00:03

PubMed articles on: Cardio-Oncology

Methods to assess radiation-induced cardiotoxicity in rodent models


Methods Cell Biol. 2023;180:127-146. doi: 10.1016/bs.mcb.2023.02.014. Epub 2023 Apr 24.

 



ABSTRACT


The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.


PMID:37892201 | PMC:PMC10604821 | DOI:10.3390/biom13101519

00:03

PubMed articles on: Cancer & VTE/PE

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study


Cancer Med. 2023 Oct 26. doi: 10.1002/cam4.6626. Online ahead of print.

 


ABSTRACT


Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.


PMID:37882602 | DOI:10.1002/aorn.14019

00:02

PubMed articles on: Cardio-Oncology

Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases


Biomolecules. 2023 Oct 13;13(10):1519. doi: 10.3390/biom13101519.

 


ABSTRACT


OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.


DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.


SETTING: PICUs within U.S. CHAT Consortium participating centers.


PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.


INTERVENTIONS: None.


MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.


CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.


PMID:37882641 | DOI:10.1097/PCC.0000000000003383

00:02

PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism


AORN J. 2023 Nov;118(5):321-328. doi: 10.1002/aorn.14019.