#Cardio vascular health

[kvchandru]

In today's fast-paced world, finding time to maintain a healthy lifestyle can feel like a daunting challenge. But what if we told you that just 30 minutes of walking each day could make a significant difference in your health and well-being? Not only is walking an accessible and free activity, but it also offers countless benefits that can enhance various aspects of your life.

https://trendingtoday2302.blogspot.com/2024/10/in-todays-fast-paced-world-finding-time.html

[hero-of-crefeld]

I just read this article and I couldn't calm down out of joy. We all know what's going to happen to John in the upcoming books, but it seems David is (finally) stepping up to the main ranks and getting the scenes he deserves. And it's going to be great!!!

„One of the great confluences of these rivers in season seven is the love triangle of Claire, Jamie and Lord John Grey (David Berry). Both Claire and John love Jamie "desperately and passionately," Roberts says. "There are so many layers and dynamics between these three people, and this season it'll definitely come to a head. I think a lot of people will fall in love with John again."

For her part, Davis says, "I cannot wait for everyone to see David Berry's performance in season seven. He's outstanding. He just kills it in this role, especially this season. He's really stepped it up."

Perhaps his performance this season will help seal the deal on the long-gestating idea of a Lord John spinoff. "Just speaking for myself, I think the Lord John series is a no-brainer," Davis says. "I would love to see that series. The books are great, and he's such an interesting character."

OMG! ❤️

Full article link:

https://www.emmys.com/news/features/onward-outlander

LOVE your blog! 🥰

Thank you so much for sending this, anon! <3

Here's a direct link to the article for anyone who wants to read it: https://www.emmys.com/news/features/onward-outlander

I apparently had many thoughts on the subject, so the rest is under the cut. :D

I have to begin with: hell yes people are going to fall in love with John! The character is so interesting, and although I find it a bit tedious that we often sometimes only get to see him as this lovesick dude who conveniently shows up to solve Jamie’s problems, I think the show actually does a decent job of portraying him. Because he’s the character you want to know more about. In a show where you have so many characters, he is the one that kind of feels like a main character even though he isn’t one. He feels nuanced and you get a sense of him actually living his life in between making appearances in the show. And that’s something I don’t necessarily get with a lot of the other characters. (Okay, I may be super biased but still!)

Introducing him more firmly into the main story through a love triangle is a good way of at least getting more LJG in our lives. I hope they change the story a bit and tone down homophobic-punches-John-in-the-face Jamie, and I think they will, since they’ve done a great job in making Jamie less conservative in other aspects, too. With regards to what happens later with John, I wonder how much they plan to include in the show. But whatever they do, I hope they don’t run through a million things in a half-assed way and then just go “anyway, that situation resolved itself, don’t worry about it.” But we’ll see.

In any case, it makes me so happy to know that there is support for an LJG spinoff! It’s so true that there is good material to draw from if they were to make it, and I think it would be really great to get a historical show that had an LGBTQ+ main character. But simultaneously, I have to admit that my expectation for such a show would be sky-high, and I would probably throw a tantrum at the smallest historical inaccuracy. (So they’d better do their research unlike DG…) I know it’s historical fiction, but it can be accurate and entertaining. (Fun take, I know) My expectations would anyway be really high because David Berry deserves the world, and that includes flawlessly written shows where he is the main character.

And speaking of David. Oh my god, anon, when I read the words “I cannot wait for everyone to see David Berry's performance in season seven. He's outstanding. He just kills it in this role, especially this season. He's really stepped it up.” my heart skipped a beat. Like I don’t have praise kink, I have a ‘praise David Berry’ kink. I cannot even begin to describe how wonderful it is to read those words. He deserves it so much. I don’t even know what to say… I just… I don’t even know. Like he doesn’t seem like the most confident person in the world, so it makes me so indescribably happy to read about people explicitly saying that he’s amazing. And also the fact that there is talk of a spinoff shows that there is sooo much love not just for Lord John but for David as well. He is the perfect LJG. My heart is so full, anon! So full! And I absolutely get why you can’t calm down out of joy, because hard same!!!

[familythings]

The Power of Happiness in Reducing Heart Attack Risks

Did you know that happiness is a key factor in reducing the risk of heart attacks? Feeling satisfied with life not only boosts mental health but can also lower the likelihood of serious cardiovascular issues. A recent study published in the Journal of the American Heart Association reveals the significant link between well-being and heart health. The Link Between Happiness and Heart…

[albonium]

it's fall everyone has covid everywhere the flu and cold viruses will make a come back soon too i'm terrified for my mom if you don't wear a mask in public fuck you you're participating directly or indirectly in the death of a lot of people's moms brothers and kids

[gabriel737]

Best Cardiologist in Sri Ganganagar – Expert Heart & Cardiovascular Care SN Hospitals is home to the best cardiologists in Sri Ganganagar, offering specialized heart care and advanced treatments. Our experienced heart cardiologists and cardiovascular surgeons provide comprehensive care, ensuring the best outcomes for heart health.

[allylikethecat]

Sorry you’re feeling sick :( but I have been so excited and patiently waiting for the NA SATVB sickfic, and I hope both you and fictional!matty are able to get some comfort <3

When I tell you yesterday I was sitting on my shower floor just letting the water hit me absolutely miserable I was just like "wow... this is how Fictional!Matty feels sorry Fictional!Matty" 😂

I am feeling a *bit* better today even though my friend/coworker called me after our big virtual team meeting and was like "WTF Ally you sound awful are you okay" and I was like "sir this is literally the best I've felt in days" and he was like "really because this is the WORST I've ever heard you sound" and for context I have known this man for six years at this point both professionally and personally (his wife is one of my best friends) and he has seen me at some very, very low points 💀

Thank you for the well wishes though! It really does mean a lot! I don't get sick very often so when I *do* get sick I am extremely dramatic about it.

I have actually officially started the NA SATVB sick fic which is exciting! It is going to be a one shot I refuse to allow it to grow past that and I am excited to eventually finish and share it especially now that it seems as if that will be happening sooner than originally thought!

Just to make sure I'm remembering correctly though- it was the Vancouver show that he showed up with the robe and the IV right? Please let me know!!

Thank you so much for reading, the well wishes, and sending this ask! I'm so glad that there will still be a NA SATVB sickfic audience even though it took me twenty thousand years to write this fic. I hope you are having a happy Tuesday and that you have a great week!

❤️Ally

[wellsunmedicityhospital]

Wellsun  Medicity is Multi specialty hospital, Healthcare service, premier medical hospitals and India's best Doctor who came together to drive their passion and commitment to providing quality healthcare such as Cardiology, Cardio Vascular Thoracic Surgery, Nephrology, Urology & Kidney Transplant, Neuro Surgery & Trauma Management, euro Surgery & Trauma Management, Pulmonary Medicine

[apoemaday]

Sex Without Love

by Sharon Olds

How do they do it, the ones who make love without love? Beautiful as dancers, gliding over each other like ice-skaters over the ice, fingers hooked inside each other’s bodies, faces red as steak, wine, wet as the children at birth whose mothers are going to give them away. How do they come to the come to the come to the God come to the still waters, and not love the one who came there with them, light rising slowly as steam off their joined skin? These are the true religious, the purists, the pros, the ones who will not accept a false Messiah, love the priest instead of the God. They do not mistake the lover for their own pleasure, they are like great runners: they know they are alone with the road surface, the cold, the wind, the fit of their shoes, their over-all cardio- vascular health — just factors, like the partner in the bed, and not the truth, which is the single body alone in the universe against its own best time.

[maounteighn]

Angela Puppington hc

Angela's heart condition is in part a result of a hereditary predisposition to cardio-vascular diseases. Had she not had those 11 pregnancies, she would've been fine. Had she had Clay from first attempt she probably would've been fine too. 10 almost full pregnancies+ 1 full pregnancy and labour+smoking/drinking+she probably also had mental health issues all multiplied to hereditary heart disease equals a weak heart. I personally vote for cardiomegaly or cardiomyopathy (all the previous causes fit the bill, pregnancy and alcohol cause heart diseases left and right anyways), it's ironically symbolic and in character for her to have died of an enlarged heart.

Clay inherited it too(it's also ironic for him to have enlarged heart by not being able to have any space for anyone in it), and so did Orel(again, the symbolism). For Clay it's just a matter of time till his first heart attack scare. For Orel – probably not, esp if he actually finds out about the inherent nature of it.

[kedreeva]

proud of: I finally got my brain sick medicated!

Good things that happened: I finally got to see my boyfriend of four years in person for the first time and I found a cat under my van (his name is Cardio-Vascular-Health now and he likes taking naps on the window sill) and I got to start cooking again after a few years of not having a kitchen

and this isn't part of the game: I just appreciate your presence on this site and how much joy you spread. both with these ask games/WIP Wednesday and such and with your passion for getting people to interact with fan creators and for just like. posting so many pictures of your animals. it always brightens my day. anyways I hope you have a good year ahead of you

Aw thank you very much for those kind words! Congrats very much on your medications, and on your new cat! I so happy you got to meet your boyfriend finally, and got the kitchen space to cook in again!!

Please enjoy Aislynn getting a quick head smoosh of greeting

[fandomshatepeoplewdisabilities]

Trigger warning for ideation…

Hi there! I just found your Tumblr while googling “Yellowjackets” and “ableism”, and I’m so glad I did. I’m a podcaster/Youtuber who covered Yellowjackets. My podcast was one of the most popular, always falling between the first and fourth spots in the charts. Unfortunately, I’ve experienced such severe ableism from the Yellowjackets fandom, that I

A) was diagnosed with PTSD from my experience

B) started getting regular panic attacks for the first time in my life.

C) tried to self-delete

D) had to step down from my podcast, while the pod that started the ableist harassment continues to gain from what they copied and stole from me.

Every day is a struggle for me to survive through this, so finding other spoonies who have been hurt by their fandom experiences is a huge deal to me. I’m glad I found you and I look forward to exploring your Tumblr further!

Kelly 💜💙💚🧡

Mod Tallys:

First of all, so glad this blog helps you. It helped for me too.

I am not in the Yellowjackets fandom, and only very vaguely know what is it about, but oh boy do I relate to the experience of being in an extremely ableist fandom to the point of harming my mental health.

Sadly don't really have any tips other than documenting all of the ableist harassment so that, as soon as the ableists try to gaslight you into thinking it wasn't that bad and it was not actually ableist, you have recites. And finding other disabled people in the fandom.

But I sadly still have not found a way to bring justice to the fandom, or even just make the majority understand just how harmful and bigoted this behavior is. I hate how always the most bigoted and abusive people get the biggest. If anyone has, please comment.

If it makes you feel lesser alone, I was and still am in the She-Ra and the Princesses of Power fandom, which always brags about being so progressive, so spoilers, they aren't. At all. Quite a lot of them are also ragingly biphobic, and quite a lot inhaled TERF ideology without any reflection, but that is another issue. (Now talking a lot about my own experience is not meant to take the focus off you, but rather as showing you that you are not alone with your experience).

This show has three canonically disabled characters, all villains (spoilers: Quite many of the crew are ableists too and refused to protect the disabled people in the fanbase, or even indirectly encouraged the harassment, even if they, too, also brag so often about how progressive they are).

One is, as much as I love that manipulative bastard, just about everything you can do wrong with face difference rep; a elf woman who had a dark magic spell she tried to do for the greater good backfire and caused her scars all over her body, she now wears a mask because she is intensely insecure about her scars, and she became first officer of the villains. But the other two are some of the best representation I ever saw - still big flaws, but compared to the garbage one usually sees - and they actually have a romance with each other. This was the first disabled4disabled romance I ever saw in any media I know, not just genre media.

They are Entrapta, an autistic woman with a knack for engineering and chaos, who defected to the villains because the good guys thought she was dead, but also really because how badly they treat her. And Hordak, a former clone slave with an unspecified but fairly explicit muscular atrophy and cardio-vascular issue, and also intense religious trauma. Yeah, he wears sci-fi armor to deal with that, which is not the best of tropes because of how far removed from reality for people with these disabilities this is, but also his self-hate and insecurities and how desperately he tries to hide his disability and how his slave master/cult leader but also even people in his own army abuse him for that... I can see myself in him so much.

And they not just bond about being the evil scientists of the evil army, but also about the ableism they faced, encouraging each other to get more confident about themselves, helping with things their disabilities make hard for them, and reassuring each other that they are worthy the way they are, flaws and disability and all. It is so touching.

Most of the fandom was, and to an extend, but most of the bullies got bored and moved on, furious about this. They tried to wrap it into social justice language, as they always do. This is pedophilia, Entrapta is a child/has the mind of a child/can't understand what she is doing. Hordak is a gross old man (because we all know all people with physical disabilities are all old people...), he is manipulating and abusing her. Ewww this is so cishet (Entrapta is canonically bi and Hordak literally wears a dress and makeup and was thrown out his cult, beside his disability, for choosing his own name, and their dynamic is very gender role subverting), Entrapta is actually aroace, shipping villains means you support colonialism... It was absolutely obvious this was about ableism, but if you called them out on this, they tried to gaslight you into "you are just to sensitive".

They constantly harassed the shippers, who almost exclusively are disabled and/or queer, also quite a few POC, to the point where seeing some ableist shit take happend daily, if I was lucky even several times a day. Faked callout posts for being a racist (liking Hordak, and fighting back against a bully who happens to be not white), a pedophile (shipping an adult autistic woman with an adult man), lesbiphobic (not focusing solely on the fan favorite lesbian ship), a colonizer (liking Hordak)... But they didn't even stop there, there are the ever present hate anons, but also deliberately triggering people, suicide baiting and death threats.

I hate admitting just how much this harmed me, because at least one of these bullies regularly stalked my blog - hope she has given up by now but honestly with that level of creep-ness I would not be surprised if she still does it - despite me blocking her, but this was just... so awful. Seeing how for most of the fandom, I should not have rights, I should not be able to choose for myself, I am not an actual human person, my sexuality is not valid but gross, I should not be in this fandom.

I feel bad that this gets to me this much, it is just online and it is just fandom - but it still hurts. Some days I only didn't left the fandom out of spite and because it is very unlikely I would find such good disabled for disabled rep again in the next time.

I definitely have trauma from this, and also from another ableist fandom that wasn't quite as obviously ableist, but it did swung by in the background, even if for me it luckily isn't quite PTSD.

Trauma from online harassment and fandom is valid. These experiences are real, no matter what the abusers and mainstream say about this.

I am so glad this blog exists to fight back and inform, or at least show disabled people in fandom that they are not alone. This is actually why I joined, despite being a bit worried about not having the spoons for this.

I am sure many of the other Mods have experiences like this too, feel free to chime in. Maybe you even have better strategies to deal with it.

Ah, I also made two (by now rather old) videos about this issue on my Youtube channel, because I was so enraged and desperate. They are just about the She-Ra fandom, but maybe they still help? Idk, feel free to ignore them if not interested or too triggering or something...

(Second part has a bit of a bad intonation quality, but maybe the content still helps)

[kvchandru]

In today's fast-paced world, finding time to maintain a healthy lifestyle can feel like a daunting challenge. But what if we told you that just 30 minutes of walking each day could make a significant difference in your health and well-being? Not only is walking an accessible and free activity, but it also offers countless benefits that can enhance various aspects of your life.

https://trendingtoday2302.blogspot.com/2024/10/in-todays-fast-paced-world-finding-time.html

[myrawjcsmicasereports]

Retinal and choroidal vascular drop out in a case of severe phenotype of Flammer Syndrome. Rescue of the ischemic-preconditioning mimicking action of endogenous Erythropoietin (EPO) by off-label intra vitreal injection of recombinant human EPO (rhEPO) by Claude Boscher in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

Background: Erythropoietin (EPO) is a pleiotropic anti-apoptotic, neurotrophic, anti-inflammatory, and pro-angiogenic endogenous agent, in addition to its effect on erythropoiesis. Exogenous EPO is currently used notably in human spinal cord trauma, and pilot studies in ocular diseases have been reported. Its action has been shown in all (neurons, glia, retinal pigment epithelium, and endothelial) retinal cells. Patients affected by the Flammer Syndrome (FS) (secondary to Endothelin (ET)-related endothelial dysfunction) are exposed to ischemic accidents in the microcirculation, notably the retina and optic nerve.

Case Presentation: A 54 years old female patient with a diagnosis of venous occlusion OR since three weeks presented on March 3, 2019. A severe Flammer phenotype and underlying non arteritic ischemic optic neuropathy; retinal and choroidal drop-out were obviated. Investigation and follow-up were performed for 36 months with Retinal Multimodal Imaging (Visual field, SD-OCT, OCT- Angiography, Indo Cyanin Green Cine-Video Angiography). Recombinant human EPO (rhEPO)(EPREX®)(2000 units, 0.05 cc) off-label intravitreal injection was performed twice at one month interval. Visual acuity rapidly improved from 20/200 to 20/63 with disparition of the initial altitudinal scotoma after the first rhEPO injection, to 20/40 after the second injection, and gradually up to 20/32, by month 5 to month 36. Secondary cystoid macular edema developed ten days after the first injection, that was not treated via anti-VEGF therapy, and resolved after the second rhEPO injection. PR1 layer integrity, as well as protective macular gliosis were fully restored. Some level of ischemia persisted in the deep capillary plexus and at the optic disc.

Conclusion: Patients with FS are submitted to chronic ischemia and paroxystic ischemia/reperfusion injury that drive survival physiological adaptations via  the hypoxic-preconditioning mimicking effect of endogenous EPO, that becomes overwhelmed in case of acute hypoxic stress threshold above resilience limits. Intra vitreal exogenous rhEPO injection restores retinal hypoxic-preconditioning adaptation capacity, provided it is timely administrated. Intra vitreal rhEPO might be beneficial in other retinal diseases of ischemic and inflammatory nature.

Key words : Erythropoietin, retinal vein occlusion, anterior ischemic optic neuropathy, Flammer syndrome, Primary Vascular Dysfunction, anti-VEGF therapy, Endothelin, microcirculation, off-label therapy.

Introduction

Retinal Venous Occlusion (RVO) treatment still carries insufficiencies and contradictions (1) due to the incomplete deciphering of the pathophysiology and of its complex multifactorial nature, with overlooking of factors other than VEGF up-regulation, notably the roles of  retinal venous tone and Endothelin-1 (ET) (2-5), and of endothelial caspase-9 activation (6). Flammer Syndrome (FS)( (Primary Vascular Dysfunction) is related to a non atherosclerotic ET-related endothelial dysfunction in a context of frequent hypotension and increased oxidative stress (OS), that alienates organs perfusion, with notably changeable functional altered regulation of blood flow (7-9), but the pathophysiology remains uncompletely  elucidated (8). FS is more frequent in females, and does not seem to be expressed among outdoors workers, implying an influence of sex hormons and light (7)(9). ET is the most potent pro-proliferative, pro-fibrotic, pro-oxidative and pro-inflammatory vasoconstrictor, currently considered involved in many diseases other than cardio-vascular ones, and is notably an inducer of neuronal apoptosis (10). It is produced by endothelial (EC), smooth vascular muscles (SVMC) and kidney medullar cells,  and binds the surface Receptors  ET-A on SVMC and ET-B on EC,  in an autocrine and paracrine fashion. Schematically, binding on SVMC Receptors (i.e. through local diffusion in fenestrated capillaries or dysfunctioning EC) and on EC ones (i.e. by circulating ET) induce respectively arterial and venous vasoconstriction, and vasodilation, the latter via Nitrite oxide (NO) synthesis. ET production is stimulated notably by Angiotensin 2, insulin, cortisol, hypoxia, and antagonized by endothelial gaseous NO, itself induced by flow shear stress. Schematically but not exclusively, vascular tone is maintained by a complex regulation of ET-NO balance (8) (10-11).  Both decrease of NO and increase of ET production are both a cause and consequence of inflammation, OS  and endothelial dysfunction, that accordingly favour vasoconstriction; in addition ET competes for L-arginine substrate with NO synthase, thereby reducing NO bioavailability, a mechanism obviated notably in carotid plaques and amaurosis fugax (reviewed in 11).

Severe FS phenotypes are rare. Within the eye, circulating ET reaches retinal VSMC in case of Blood-Retinal-Barrier (BRB) rupture and diffuses freely via the fenestrated choroidal circulation, notably around the optic nerve (ON) head behind the lamina cribrosa, and may induce all pathologies related to acute ocular blood flow decrease (2-3)(5)(7-9). We previously reported two severe cases with rapid onset of monocular cecity and low vision, of respectively RVO in altitude and non arteritic  ischemic optic neuropathy (NAION) (Boscher et al, Société Francaise d'Ophtalmologie and Retina Society, 2015 annual meetings).

Exogenous Recombinant human EPO (rhEPO) has been shown  effective in humans for spinal cord injury (12), neurodegenerative and chronic kidney diseases (CKD) (reviewed in 13). Endogenous EPO is released physiologically in the circulation by the kidney and liver; it may be secreted in addition by all cells in response to hypoxic stress, and it is the prevailing pathway induced via genes up-regulation by the transcription factor Hypoxia Inducible Factor 1 alpha, among angiogenesis (VEGF pathway), vasomotor regulation (inducible NO synthase), antioxidation, and energy metabolism (14). EPO Receptor signaling induces cell proliferation, survival and differentiation (reviewed in 13), and targets multiple non hematopoietic pathways as well as the long-known effect on erythropoiesis (reviewed in 15). Of particular interest here, are its synergistic anti-inflammatory, neural antiapoptotic (16) pro-survival and  pro-regenerative (17) actions upon hypoxic injury, that were long-suggested to be also indirect, via blockade of ET release by astrocytes, and assimilated to ET-A blockers action (18). Quite interestingly, endogenous EPO’s pleiotropic effects were long-summarized (back to 2002), as “mimicking hypoxic-preconditioning” by Dawson (19), a concept applied to the retina (20). EPO Receptors are present in all retinal cells and their rescue activation targets all retinal cells, i.e. retinal EC, neurons (photoreceptors (PR), ganglion (RGG) and  bipolar cells), retinal pigment epithelium (RPE) osmotic function through restoration of the BRB, and  glial cells (reviewed in 21), and the optic nerve (reviewed in 22).  RhEPO has been tested experimentally in animal models of glaucoma, retinal ischemia-reperfusion (I/R) and light phototoxicity, via multiple routes (systemic, subconjunctival, retrobulbar and intravitreal injection (IVI) (reviewed in 23), and used successfully via IVI in human pilot studies, notably first in diabetic macular edema (24) (reviewed in 25 and 26). It failed to improve neuroprotection in association to corticosteroids in optic neuritis, likely for bias reasons (reviewed in 22). Of specific relation to the current case, it has been reported in NAION (27) (reviewed in 28) and traumatic ON injury (29 Rashad), and in one case of acute severe central RVO (CRVO) (Luscan and Roche, Société Francaise d’Ophtalmologie 2017 annual meeting). In addition EPO RPE gene therapy was recently suggested to prevent retinal degeneration induced by OS in a rodent model of dry Age Macular Degeneration (AMD) (30).

Case Report Presentation

This 54 years female patient was first visited on March 2019 4th, seeking for second opinion for ongoing vision deterioration OR on a daily basis, since around 3 weeks. Sub-central RVO (CRVO) OR had been diagnosed on February 27th; available SD-OCT macular volume was increased with  epiretinal marked hyperreflectivity, one available Fluorescein angiography picture showed a non-filled superior CRVO, and a vast central ischemia involving the macular and paraoptic territories. Of note there was ON edema with a para-papillary hemorrage nasal to the disc on the available colour fundus picture.

At presentation on March 4, Best Corrected Visual Acuity (BCVA) was reduced at 20/100 OR (20/25 OS). The patient described periods of acutely excruciating retro-orbital pain in the OR. Intraocular pressure was normal, at 12 OR and 18 OS (pachymetry was at 490 microns in both eyes). The dilated fundus examination was similar to the previous color picture and  did not disclose peripheral hemorrages recalling extended peripheral retinal ischemia. Humphrey Visual Field disclosed an altitudinal inferior scotoma and a peripheral inferior scotoma OR and was in the normal range OS, i.e. did not recall normal tension glaucoma OS . There were no papillary drusen on the autofluorescence picture, ON volume was increased  (11.77 mm3 OR versus 5.75 OS) on SD-OCT (Heidelberg Engineering®) OR,  Retinal Nerve Fiber (RNFL) and RGC layers thicknesses were normal  Marked epimacular hypereflectivity OR with foveolar depression inversion, moderately increased total volume and central foveolar thickness (CFT) (428 microns versus 328 OS), and a whitish aspect of the supero-temporal internal retinal layers recalling ischemic edema, were present . EDI CFT was incresead at 315 microns (versus 273 microns OS), with focal pachyvessels on the video mapping . OCT-Angiography disclosed focal perfusion defects in both the retinal and chorio-capillaris circulations , and central alterations of the PR1 layer on en-face OCT

Altogether the clinical picture evoked a NAION with venous sub-occlusion, recalling Fraenkel’s et al early hypothesis of an ET interstitial diffusion-related venous vasoconstriction behind the lamina cribrosa (2), as much as a rupture of the BRB was present in the optic nerve area (hemorrage along the optic disc). Choroidal vascular drop-out was suggested by the severity and rapidity of the VF impairment (31). The extremely rapid development of a significant “epiretinal membrane”, that we interpreted as a reactive - and protective, in absence of cystoid macular edema (CME) - ET 2-induced astrocytic proliferation (reviewed in 32), was as an additional  sign of severe ischemia.

The mention of the retro-orbital pain evoking a “ciliary angor”, the absence of any inflammatory syndrome and of the usual metabolic syndrome in the emergency blood test, oriented the etiology towards a FS. And indeed anamnesis collected many features of the FS, i.e. hypotension (“non dipper” profile with one symptomatic nocturnal episode of hypotension on the MAPA), migrains, hypersensitivity to cold, stress, noise, smells, and medicines, history of a spontaneously resolutive hydrops six months earlier, and of paroxystic episods of vertigo (which had driven a prior negative brain RMI investigation for Multiple Sclerosis, a frequent record among FS patients (33) and of paroxystic visual field alterations (7)(9), that were actually recorded several times along the follow-up.

The diagnosis of FS was eventually confirmed in the Ophthalmology Department in Basel University on April 10th, with elevated retinal venous pressure (20 to 25mmHg versus 10-15 OS) (4)(7)(9), reduced perfusion in the central retinal artery and veins on ocular Doppler (respectively 8.3 cm/second OR velocity versus 14.1 mmHg OS, and 3.1/second OR versus 5.9 cm OS), and impaired vasodilation upon flicker light-dependant shear stress on the Dynamic Vessel Analyser testing (7-9). In addition atherosclerotic plaques were absent on carotid Doppler.

On March 4th, the patient was at length informed about the FS, a possible off label rhEPO IVI, and a related written informed consent on the ratio risk-benefits was delivered.

By March 7th, she returned on an emergency basis because of vision worsening OR. VA was unchanged, intraocular pressure was at 13, but Visual Field showed a worsening of the central and inferior scotomas with a decreased foveolar threshold, from 33 to 29 decibels. SD-OCT showed a 10% increase in the CFT volume.

On the very same day, an off label rhEPO IVI OR (EPREX® 2000 units, 0,05 cc in a pre-filled syringe) was performed in the operating theater, i.e. the dose reported  by Modarres et al (27), and twenty times inferior to the usual weekly intravenous dose for treatment of chronic anemia secondary to CKD. Intra venous acetazolamide (500 milligrams) was performed prior to the injection, to prevent any increase in intra-ocular pressure. The patient was discharged with a prescription of chlorydrate betaxolol (Betoptic® 0.5 %) two drops a day, and high dose daily magnesium supplementation (600 mgr).

Incidentally the patient developed bradycardia the day after, after altogether instillation of 4 drops of betaxolol only, that was replaced by acetazolamide drops, i.e. a typical hypersensitivity reaction to medications in the FS (7)(9).

Subjective vision improvement was recorded as early as D1 after injection. By March 18 th, eleven days post rhEPO IVI, BCVA was improved at 20/63, the altitudinal scotoma had resolved (Fig. 5), Posterior Vitreous Detachment had developed with a disturbing marked Weiss ring, optic disc swelling had decreased; vasculogenesis within the retinal plexi and some regression of PR1 alterations  were visible on OCT-en face. Indeed by 11 days post EPO significant functional, neuronal and vascular rescue were observed, while the natural evolution had been seriously vision threatening.

However cystoid ME (CME) had developed . Indo Cyanin Green-Cine Video Angiography (ICG-CVA) OR, performed on March 23, i.e. 16 days after the rhEPO IVI, showed a persistent drop in ocular perfusion: ciliary and central retinal artery perfusion timings were dramatically delayed at respectively 21 and 25 seconds, central retinal vein perfusion initiated by 35 seconds, was pulsatile, and completed by 50 seconds only (video 3). Choroidal pachyveins matching the ones on SD-OCT video mapping were present in the temporal superior and inferior fields, and crossed the macula; capillary exclusion territories were present in the macula and around the optic disc.

By April 1, 23 days after the rhEPO injection, VA was unchanged, but CME and perfusion voids in the superficial deep capillary plexi and choriocapillaris were worsened, and optic disc swelling had recurred back to baseline, in a context of repeated episodes of systemic hypotension; and actually Nifepidin-Ratiopharm® oral drops (34), that had been delivered via a Temporary Use Authorization from the central Pharmacology Department in Assistance Publique Hopitaux de Paris, had had to be stopped because of hypersensitivity.

A second off label rhEPO IVI was performed in the same conditions on April 3, i.e. approximately one month after the first one.

Evolution was favourable as early as the day after EPO injection 2: VA was improved at 20/40, CME was reduced, and perfusion improved in the superficial retinal plexus as well as in the choriocapillaris. By week 4 after EPO injection 2, CME was much decreased, i.e. without anti VEGF injection. On august 19th, by week 18 after EPO 2, perfusion on ICG-CVA was greatly improved , with ciliary timing at 18 seconds, central retinal artery at 20 seconds and venous return from 23 to 36 seconds, still pulsatile. Capillary exclusion territories were visible in the macula and temporal to the macula after the capillary flood time that went on by 20.5 until 22.5 seconds (video 4); they  were no longer persistent at intermediate and late timings.

Last complete follow-up was recorded on January 7, 2021, at 22 months from EPO injection 2. BCVA was at 20/40, ON volume had dropped at 7.46 mm3, a sequaelar superior deficit was present in the RNFL  with some  corresponding residual defects on the inferior para central Visual Field , CFT was at 384 mm3 with an epimacular hyperreflectivity without ME, EDI CFT was dropped at 230 microns. Perfusion on ICG-CVA was not normalized, but even more improved, with ciliary timing at 15 seconds, central retinal artery at 16 seconds and venous return from 22 to 31 seconds, still pulsatile , indicating that VP was still above IOP. OCT-A showed persisting perfusion voids, especially at  the optic disc and within the deep retinal capillary plexus. The latter were present at some degree in the OS as well . Choriocapillaris and PR1 layer were dramatically improved.

Last recorded BCVA was at 20/32 by February 14, 2022, at 34 months from EPO 2. SD-OCT showed stable gliosis hypertrophy and mild alterations of the external layers .

Discussion

What was striking in the initial clinical phenotype of CRVO  was  the contrast between the moderate venous dilation,  and the intensity of ischemia, that were illustrating the pioneer hypothesis of Professor Flammer‘s team regarding the pivotal role of ET in VO (2), recently confirmed (3)(35), i.e. the local venous constriction backwards the lamina cribrosa, induced by diffusion of ET-1 within the vascular interstitium, in reaction to hypoxia. NAION was actually the primary and prevailing alteration, and ocular hypoperfusion was confirmed via ICG-CVA, as well as by the ocular Doppler performed in Basel. ICG-CVA confirmed the choroidal drop-out suggested by the severity of the VF impairment (31) and by OCT-A in the choriocapillaris. Venous pressure measurement, which instrumentation is now available (8), should become part of routine eye examination in case of RVO, as it is key to guide cases analysis and personalized therapeutical options.

Indeed, the endogenous EPO pathway is the dominant one activated by hypoxia and is synergetic with the VEGF pathway, and coherently it is expressed along to VEGF in the vitreous in human RVO (36). Diseases develop when the individual limiting  stress threshold for efficient adaptative reactive capacity gets overwhelmed. In this case by Week 3 after symtoms onset,  neuronal and vascular resilience mechanisms were no longer operative, but the BRB, compromised at the ON, was still maintained in the retina.

As mentioned in the introduction, the scientific rationale for the use of EPO was well demonstrated by that time, as well as the capacities of exogenous EPO to mimic endogenous EPO vasculogenesis, neurogenesis and  synaptogenesis, restoration of  the balance between ET-1 and NO. Improvement of chorioretinal blood flow was actually illustrated by the evolution of the choriocapillaris perfusion on repeated OCT-A and ICG-CVA. The anti-apoptotic effect of EPO (16) seems as much appropriate in case of RVO as the caspase-9 activation is possibly another overlooked co-factor (6).

All the conditions for translation into off label clinical use were present: severe vision loss with daily worsening and  unlikely spontaneous favourable  evolution, absence of toxicity in the human pilot studies, of contradictory comorbidities and co-medications, and of context of intraocular neovascularization that might be exacerbated by EPO (37).

Why didn’t we treat the onset of CME by March 18th, i.e. eleven days after EPO IVI 1, by anti-VEGF therapy, the “standard-of-care” in CME for RVO ?

In addition to the context of functional, neuronal and vascular improvements obviated by rhEPO IVI by that timing in the present case, actually anti VEGF therapy does not address the underlying causative pathology. Coherently, anti-VEGF IVI :  1) may not be efficient in improving vision in RVO, despite its efficiency in resolving/improving CME (usually requiring repeated injections), as shown in the Retain study (56% of eyes with resolved ME continued to loose vision)(quoted in (1) 2) eventually may be followed by serum ET-1 levels increase and VA reduction (in 25% of cases in a series of twenty eyes with BRVO) (38) and by increased areas of non perfusion in OCT-A (39). Rather did we perform a second hrEPO IVI, and actually we consider open the question whether the perfusion improvement, that was progressive, might have been accelerated/improved via repeated rhEPO IVI, on a three to four weeks basis.

The development of CME itself, involving a breakdown of the BRB, i.e. of part of the complex  retinal armentorium resilience to hypoxia, was somewhat paradoxical in the context of improvement after the first EPO injection, as EPO restores the BRB (24), and as much as it was suggested that EPO inhibits glial osmotic swelling, one cause of ME, via VEGF induction (40). Possible explanations were: 1) the vascular hyperpermeability induced by the up-regulation of VEGF gene expression via EPO (41) 2) the ongoing causative disease, of chronic nature, that was obviated by the ICG-CVA and the Basel investigation, responsible for overwhelming the gliosis-dependant capacity of resilience to hypoxia 3) a combination of both. I/R seemed excluded: EPO precisely mimics hypoxic reconditioning as shown in over ten years publications, including in the retina (20), and as EPO therapy is part of the current strategy for stabilization of the endothelial glycocalix against I/R injury (42-43). An additional and not exclusive possible explanation was the potential antagonist action of EPO on GFAP astrocytes proliferation, as mentioned in the introduction (18), that might have counteracted the reactive protective hypertrophic gliosis, still fully operative prior to EPO injection, and that was eventually restored during the follow-up, where epiretinal hyperreflectivity without ME and ongoing chronic ischemia do coincide (Fig. 6 and video 6), as much as it is unlikely that EPO’s effect would exceed one month (cf infra). Inhibition of gliosis by EPO IVI might have been also part of the mechanism of rescue of RGG, compromised by gliosis in hypoxic conditions (44). Whatever the complex balance initially reached, then overwhelmed after EPO IVI 1, the challenge was rapidly overcome by the second EPO IVI without anti-VEGF injection, likely because the former was powerful enough to restore the threshold limit for resilience to hypoxia, that seemed no longer reached again during the relapse-free follow-up. Of note, this “epiretinal membrane “, which association to good vision is a proof of concept of its protective effect, must not be removed surgically, as it would suppress one of the mecanisms of resilience to hypoxia.

To our best knowledge, ICG-CVA was never reported in FS; it allows real time evaluation of the ocular perfusion and illustration of the universal rheological laws that control choroidal blood flow as well. Pachyveins recall a “reverse” veno-arteriolar reflex in the choroidal circulation, that is NO and autonomous nervous system-dependant, and that we suggested to be an adaptative choroidal microcirculation process to hypoxia (45).  Their persistence during follow-up accounts for a persisting state of chronic ischemia.

The optimal timing for reperfusion via rhEPO in a non resolved issue:

in the case reported by Luscan and Roche, rhEPO IVI was performed on the very same day of disease onset, where it induced complete recovery from VA reduced at counting fingers at 1 meter, within 48 hours. This clinical human finding is on line with a recent rodent stroke study that established the timings for non lethal versus lethal ischemia of the neural and vascular lineages, and the optimized ones for beneficial reperfusion: the acute phase - from Day 1 where endothelial and neural cells are still preserved,  to Day 7 where proliferation of pericytes and Progenitor Stem Cells are obtainable - and the chronic stage, up to Day 56, where vasculogenesis, neurogenesis and functional recovery are still possible, but with uncertain efficiency (46). In our particular case, PR rescue after rhEPO IVI 1 indicated that Week 3 was still timely. RhEPO IVI  efficacy was shown to last between one (restoration of the BRB)  and four weeks (antiapoptotic effect) in diabetic rats (24). The relapse after Week 3 post IVI 1 might indicate that it might be  approximately the interval to be followed, should repeated injections be necessary.

The bilateral chronic perfusion defects on OCT-A at last follow-up indicate that both eyes remain in a condition of chronic ischemia and I/R, where endogenous EPO provides efficient ischemic pre-conditioning, but is potentially susceptible to be challenged during episodes of acute hypoxia that overwhelm the resilience threshold.

Conclusion

The present case advocates for individualized medicine with careful recording of the medical history, investigation of the systemic context, and exploiting of the available retinal multimodal imaging for accurate analytical interpretation of retinal diseases and their complex pathophysiology. The Flammer Syndrome is unfortunately overlooked in case of RVO; it should be suspected clinically in case of absence of the usual vascular and metabolic context, and in case  of elevated RVP. RhEPO therapy is able to restore the beneficial endogenous EPO ischemic pre-conditioning in eyes submitted to challenging acute hypoxia episodes in addition to chronic ischemic stress, as in the Flammer Syndrome and fluctuating ocular blood flow, when it becomes compromised by the overwhelming of the hypoxic stress resilience threshold. The latter physiopathological explanation illuminates the cases of RVO where anti-VEGF therapy proved functionally inefficient, and/or worsened retinal ischemia. RhEPO therapy might be applied to other chronic ischemia and I/R conditions, as non neo-vascular Age Macular Degeneration (AMD), and actually EPO was listed in 2020 among the nineteen promising molecules in AMD in a pooling of four thousands (47).

[familythings]

Anger and Heart Health: The Connection You Need to Know

Anger is an emotion we all feel, but it can harm your heart health. It can damage your relationships and lead to bad choices, but it can also negatively affect your heart. Let’s explore how anger impacts your heart and what steps you can take. The Heart Attack Risk When you get angry, your body releases stress hormones like adrenaline and cortisol. This can lead to symptoms such as flushed…

[bitchfitch]

my mother is entering my cat and mule in a charity pet costume contest benefitting a doctor's without borders style group of nurses. The mule is going to be dressed up as Jesus, and the cat a cardiologist bc his name is Cardio-Vascular-Health and I think that would be funny

this is he:

the competition is primarily going to be voted on by nursing students and faculty. so folk who will not be wigged out by an anatomically correct heart, but who still might fall into a more normy aesthetic preference group.

The heart will be done in crochet either way bc I can't be fucked to spend more than 30 minutes on it.

[albonium]

the lab tech told me there's a huge covid wave right now (how surprising lol)

it's always the right time to start masking with a well fitting ffp2 or n95 mask, for your health and the health of your family friends and community including people with disabilities and health problems

first of all covid is airborne it means it behaves in the air like a deodorant or an airwick spray. staying at a distance from someone will only spare you some of the droplets but not the whole thing.

covid often causes lots of different issues in the human body, even when it's an asymptomatic infection, regardless of age and health: cardio vascular system, lungs, nervous system/brain/early dementia/memory/depression, immune system, taste smell vision and hearing loss. there's is about 20% chance of getting long covid each time you get infected and risk increase with the number of infections even if they're asymptomatic. long covid can take different forms but basically people are disabled with lots of conditions making making their life quality shit. some are bed bound with symptoms similar to pots or neurological diseases.

the vaccine only prevents severe reactions to the infection and only works for some variants. if you haven't gotten a booster in the last 6 months/year it's not effective anymore

the main tools we have are well fitting ffp2/ffp3/n95 masks, air ventilation/purifying and testing