#amyloidosis

[didanawisgi]

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Abstract

Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

[teachingrounds]

Today's less common nuclear medicine study is Tc-99m-pyrophosphate (PYP) for evaluation of suspected cardiac amyloidosis. In such patients, PYP has excellent specificity for TTR amyloidosis.

Case shows a planar image (left) from a PYP scan of an elderly patient with suspected cardiac amyloidosis. SPECT CT (right) confirms that the uptake localizes to the myocardium. Based on ASNC guidelines, this is "strongly suggestive" of TTR amyloidosis (myocardial uptake greater than rib uptake).

Note that a negative scan essentially rules out TTR amyloidosis but does not exclude AL amyloidosis, and patients with negative scans may require myocardial biopsy.

[wedgemccloud]

As there’s not really any information on it above, amyloidosis (as might be recognized by name by the House, MD enjoyers, which overlap a decent bit with the Code Geass crowd) is not a single disease but a grouping of similar diseases that rise due to excess or otherwise abnormal proteins that build up in tissue and organs, causing a lot of problems in various parts of the body as it interferes with proper tissue and organ function.

Due to the combination of the rarity and the over thirty types of amyloidosis, some of which are hereditary and some of which are not, it can incredibly hard to diagnose because the symptoms are vague and varied.

Part of why this can be difficult is some of its most common symptoms are incredibly common with many other conditions - fatigue, weight loss, shortness of breath, palpitations, and feeling faint with standing. One of the most noticeable symptoms that is different from many other fatigue-related conditions is what’s known as a peripheral edema, which is a form of swelling caused by an accumulation of fluid. This is still tricky, however, as such an edema is still a symptom of other autoimmune issues (including lupus); anemia; heart, kindey, and liver issues; or merely a comorbidity with other issues from generally sedentary lifestyle, namely prolonged sitting or standing without moving.

That’s why the abnormal proteins are such an important point. They can be one of the most noticeable aspects to test for, namely when found in the urine, along with issues such as enlarged organs due to said protein buildup or unexplained polyneuropathy, which is when multiple peripheral nerves are presenting problems, in particular with no immediate explanation. As the peripheral nerves are nerves beyond the brain and spinal cord, this is another area where diagnosis can take time, as this could present as tingling, numbness, or pain in the extremities, often in the same area or on the same side, but in amyloidosis, where protein might be traveling through the body and building up in multiple places, it may instead present polyneuropathic symptoms in more spread out or unrelated places.

Due to all of the variables in presentation, this is a disease that has to be confirmed via a biopsy, as it presents in ways that overlaps with a lot of autoimmune disorders. This means that a lot of things have to be tested for and ruled out. You won’t be able to self-diagnose something like that so you need to be communicating with your doctor(s) and try to keep yourself informed on the condition and what symptoms you are experiencing.

Early diagnosis is key to a condition such as this as, like many similar conditions, there is no cure. Amyloidosis treatment is about care and symptom management, which is easier the earlier it is detected.

In a bit of irony, it appears that this month is Amyloidosis Awareness Month, as well. As I’m not in any way a professional here or someone personally experienced with Amyloidosis, it would be good to take some time to do further research if you feel any of this relates to something you might be experiencing, especially if any symptoms you are experiencing are currently unexplained.

Takahiro Kimura, also known as the Character designer of Code Geass, just passed away.

He died from amyloidosis. His wife (and colorist of his most well known artwork) wants people to learn more about this disease so that it can be noticed and treated more efficiently.

He was the Character designer of various well known anime, and amongst them, of Code Geass, with Clamp, they designed most of the characters and he redesigned them with his signature style, adding some well known features (Like Lelouch's longs finger and hand work)

This man is one of the main reasons I fell in love with this show in 2006, his artworks and his designs gave Code Geass an unique flavor and his design of Lelouch is unmatched.

Rest in peace, Takahiro Kimura sensei, thanks for all of the artwork, the designs, the episodes and the memories. You will be remembered. Adding two of my favorite work of his for Code Geass, Lelouch of the Rebellion, and Akito the exiled.

[ijcimr]

Localised Cutaneous Amyloidosis of the Glans Penis: A Case Report and Review of the Literature by Victoria Hyett in International Journal of Clinical Images and Medical Reviews 

Abstract

Amyloidosis represents a notable cause of morbidity within the developed world. Urological presentations of systemic or localised amyloidosis are rare, with penile amyloidosis being poorly reported. We performed a literature review investigating cases of penile cutaneous amyloidosis via the PubMed database during March 2020, in conjunction with clinical review of a local patient presenting with a penile lesion. Our patient is a 60-year-old uncircumcised, caucasian male presenting with a longstanding history of 2 irregular lesions affecting his glans penis and a further 2 lesions affecting the inner surface of his prepuce. He underwent excision biopsy of the largest lesion which represented cutaneous amyloid deposits. He underwent immunological testing for systemic disease which was negative.

In current literature, there are 13 cases of cutaneous amyloidosis affecting the glans penis, with 1 of those having evidence of extra genitourinary amyloid deposits. All the documented cases were treated with local excision and investigation for systemic disease. It is important to recognise alternative diagnoses in patients presenting with penile lesions. Despite cutaneous amyloidosis mimicking malignancy macroscopically, the morbidity and mortality is lower in comparison to penile cancer. Treatment remains surgical excision of the lesion and further investigations to exclude systemic disease.

Introduction

Amyloidosis is a notable cause of morbidity, and in some cases mortality within the developed world. Urological presentations of systemic or localised amyloidosis are rare, with primary penile amyloidosis being poorly reported in the literature. It can commonly mimic malignancy on imaging and macroscopically, thus representing an important differential diagnosis to be aware of when examining and investigating a penile lesion.

Case Presentation

A 60-year-old uncircumcised, Caucasian male was referred with multiple longstanding granular lesions of his penis.  His past medical history included hypertension and insulin dependent type 2 diabetes. On initial assessment there were two irregular granular lesions on his glans penis and two further similar lesions on the inner prepuce. These were initially thought to be malignant and an excision biopsy of the largest one was performed.

The histopathological examination showed an abundance of relatively amorphous pink material in the superficial to mid dermis with positive Congo red staining and mild apple-green birefringence in keeping with cutaneous amyloidosis. Further analysis with immunohistochemical staining of the sample by the National Amyloidosis Centre confirmed this result and determined this to be of the AL Kappa subtype.

Following investigation under the care of the haematology department with serum free serum light chains, electrophoresis and Bence Jones’ protein, there was no evidence of systemic amyloidosis or multiple myeloma. A diagnosis of cutaneous AL amyloidosis of Kappa subtype affecting the glans penis and prepuce was made.

The patient underwent a circumcision for localised treatment of the remaining preputial lesions. The remaining glandular one was deemed high risk for meatal stenosis due to its proximity to the urethral meatus and therefore not excised.

The patient remains well under yearly review from the National Amyloidosis Centre.

Discussion

The term ‘Amyloid’ was first coined by Virchow in the 19th century to describe a macroscopic tissue abnormality characterised by a positive iodine staining reaction. Subsequent technological advancements in light microscopy furthered Virchow’s description to include distinct birefringence of the amyloid deposits when stained with Congo red dye [1].

The pathophysiology of amyloidosis stems from a failure of proteolysis of misfolded proteins resulting in oligomeric conglomerates referred to as amyloid fibrils. As amyloidosis is caused by misfolded proteins, there are multiple classifications of the disease specifically related to the original protein involved. All of the involved proteins may form extracellular deposits and lead to subsequent organ dysfunction [2]. The most common subtypes of amyloidosis include amyloid light chain (AL), the origin of which is an immunoglobulin arising from plasma cells, and amyloid associated (AA), arising from a non-immunoglobulin synthesised by the liver. Further classification can be made by the clinical presentation of the proteinaceous deposit; whether it be systemic or localised, and the clinical syndrome it produces.

The amyloid Light Chain (AL) subtype is characterized by clonal plasma cell dyscrasia, similarly to multiple myeloma [3]. This results in a failure to produce the classical alpha-helix configuration of either kappa or lambda light chains, instead producing a beta-pleated sheet which is inherently insoluble. Classically there is involvement of the kidneys, heart or nervous system however involvement of many organ systems has been documented.

Cutaneous amyloid deposits can be seen in both systemic and localized disease. Commonly up to 40% of systemic AL amyloidosis sufferers complain of epidermal disease, which reflects amyloid deposition within the capillaries of the skin involved. Cutaneous disease typically presents as petechiae or purpuric lesions, yellow macular or nodular lesions. There are also macular and lichen subtypes which can be associated with systemic connective tissue diseases.

Statistically, within the UK the age-adjusted prevalence of amyloidosis is between 5.1 and 12.8 per 1 million per year*. Approximately 10-20% of cases remain localised, with the remainder of cases being classified as systemic disease. Although the localised form is rarer, it carries a better prognosis [5]. Rarer still is localised penile amyloidosis, with only 14 documented cases, including ours, on literature review.

Merika et al. comments on the low prevalence of systemic disease in those presenting with cutaneous penile amyloid lesions as the primary presenting complaint. Their study also highlights the increased rate of primary nodular amyloidosis amongst those with penile cutaneous lesions [4]. Of the confirmed cases of cutaneous amyloidosis of the glans penis, only one reported a second site affected, namely the trachea. This was subsequently found to be a lone deposit, with no further evidence of widespread disease identified; however, this does not exclude the possibility of this representing systemic amyloidosis [16].

Of the cases identified, most were diagnosed on a serological and histological basis, more in depth modalities such as serum amyloid protein component (SAP) scintigraphy and genetic testing were not performed routinely. SAP scintigraphy is highly sensitive for AL and AA amyloidosis (90% for both subtypes), with a specificity of 93%. The use of SAP scintigraphy may give a more definitive answer regarding the presence of systemic disease however the modiality itself is often not available in local centres [17,18].

Treatment of the lesions remains case dependent and requires a multi-disciplinary approach [19]. The underlying amyloid subtype also greatly influences management. In systemic AL amyloidosis, treatment aims to suppress plasma cell production of amyloid which predominantly involves using dexamethasone and mephalan, an oral chemotherapeutic agent, alongside supportive care for the underlying organs involved. Similarly, AA amyloidosis requires management of the underlying disease process often involving immunomodulation [19]. Localised cutaneous amyloidosis is typically managed by surgical excision, or laser ablation, systemic chemotherapeutic agents are usually not employed due to their side effect profile [16]. The majority of cases reported were treated with local excision as in our case.

Conclusion

These cases highlight the importance of consideration of alternative diagnoses in patients presenting with cutaneous penile lesions. Fortunately, despite penile cutaneous amyloidosis mimicking malignancy, the morbidity and mortality are low due to the low incidence of systemic amyloidosis in patients who present with a penile lesion. Treatment remains local excision of the lesion, histological and immunochemical confirmation of the amyloid subtype and further investigations to exclude systemic disease. Consideration could be made for the introduction of SAP scintigraphy in these cases, however the benefit of this remains unclear with such a small demographic to review.

For more details: https://ijcimr.org/editorial-board/

[engineeringhulk]

Amyloidosis: Causes, Risk Factors, diagnosis & treatment

Amyloidosis is a rare, progressive, and often fatal condition caused by the accumulation of abnormal proteins called amyloid in various organs and tissues throughout the body. 

Amyloid is an abnormal protein usually produced by the body as a response to an injury or infection. In amyloidosis, the body has an excessive amount of amyloid, accumulating in the organs and tissues, causing damage and dysfunction. View More.

[hopeinthebox]

tagged by the lovely natalia <33 @jiminsproof a bit ago to reveal some "lasts" so, without further ado:

last song: american teenager, ethel cain - song of the year for the second year running, i fear. preacher's daughter you will always be famous

last movie: freaky friday - jamie lee curtis AND lindsay lohan milf performances???? five stars. put pink slip's take me away on spotify immediately

currently watching: house m.d. - binged my way through six seasons already and i'm showing no signs of slowing down. at this point i'm one more character playlist curation away from being institutionalised

currently reading: coded messages that kim taehyung leaves for me in his promotions and mvs. oh and high fidelity

current obsession: jungle's music videos. back on 74 was obviously the catalyst here but they're all phenomenal. additionally i have a pretty serious below deck problem

and there you have it. tagging a handful of favs if you feel so inclined: @cordiallyfuturedwight @aprylynn @pauls-mccharmly @somebodydoeslove @banghwa @monismochi @eoieopda @btscontentenjoyer @letmelovekoo @spicyclematis

[carnival-phantasm]

How the fuck am I getting all these insane cases within 2 months of starting clinical medicine residency??

[coherentmicom]

https://www.timessquarereporter.com/health/hereditary-amyloidosis-market-is-estimated-to-witness-high-growth-owing-to-increasing-prevalence-of-amyloidosis

[creativeera]

IoT and Virtual Hospital Industry: Global IoT Enabling Next Generation Virtual Hospital

The healthcare industry is embracing new digital technologies at a rapid pace to improve patient outcomes and transform the delivery of care. Internet of Things (IoT) powered solutions are connecting medical devices, integrating telehealth capabilities, and enabling new care models like virtual hospitals that remove geographic barriers. By 2023, IoT healthcare spending is projected to reach $217 billion globally as innovations reshape every aspect of the patient experience from diagnosis to long-term wellness. Connecting Medical Devices with IoT and Virtual Hospital Industry At the core of Global IoT and Virtual Hospital is their ability to remotely monitor patients anytime from anywhere. This relies on medical devices being networked and sensors wirelessly transmitting vital sign data in real-time to the cloud for analysis. IoT is enabling a wide range of devices from blood pressure cuffs and glucose monitors to EKG and pulse oximetry equipment to seamlessly integrate with electronic health records systems. Doctors can easily access streams of patient data via mobile or web applications to track recovery, identify issues early, and proactively adjust care plans as needed from a distance. For example, IoT enabled ventilators allow respiratory therapists to monitor lung function remotely for COPD and asthma patients at high risk of exacerbations. Delivering Telehealth at Scale One of the key benefits of IoT powered virtual hospitals is their ability to provide telehealth services to many more patients across broader geographies. Instead of relying on in-person clinic or hospital visits which can be time-consuming and costly for those in remote areas, IoT infrastructure facilitates real-time video consultations, remote patient monitoring, and live specialist evaluations anytime via mobile or web. This improves access to quality care for underserved communities worldwide. Leading health systems are implementing IoT ecosystems that seamlessly integrate telehealth capabilities like virtual check-ins, remote patient monitoring, and medical device data straight into their telemedicine portals and workflows. The Doximity platform, for example, connects over 560,000 physicians virtually to deliver telehealth at an unmatched scale. Transforming Care Delivery Models IoT is revolutionizing traditional care delivery models through new virtual hospital concepts that reimagine where and how healthcare is provided. Remote patient monitoring is shifting many services like post-acute care, senior care, and chronic disease management to the home. U.S. virtual health provider BestDOT utilizes an IoT platform to enable full service hospitals without physical infrastructure by leveraging connected medical equipment, EHR integrations, telehealth carts and a care coordination system available anywhere. Their virtual hospitals can stand up pop-up clinics or replace facilities damaged by natural disasters, improving both capacity and disaster response. Get more insights on Global IoT and Virtual Hospital

About Author:

Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc. (https://www.linkedin.com/in/money-singh-590844163)

[noisycowboyglitter]

Empowerment Through Art: "Amyloidosis Is A Journey I Never Planned" Butterfly Products

"The Butterfly's Embrace: Navigating the Uncharted Path of Amyloidosis"

The butterfly, with its remarkable metamorphosis, has become a profound symbol in the journey of those faced with the challenges of amyloidosis. This delicate winged creature, once a humble caterpillar, now represents the resilience, adaptability, and transformative power that is so deeply needed when confronting this rare and complex disease.

Buy now:19.95$

For those who have had amyloidosis thrust upon them, the butterfly's journey becomes a poignant metaphor for their own experiences. Like the caterpillar's remarkable transition, those affected by amyloidosis must embrace a process of profound change, shedding the familiar to emerge as a new, resilient self.

The butterfly's fragile yet determined nature mirrors the daily struggles and triumphs of amyloidosis patients and their loved ones. It is a reminder that even in the face of the unknown, growth and renewal are possible – that the chrysalis of adversity can yield the vibrant wings of strength and perseverance.

Buy now

In the embrace of the butterfly, the amyloidosis community finds solace, inspiration, and the unwavering belief that, despite the uncharted path before them, they too can undergo a remarkable transformation. The butterfly's gentle fluttering becomes a symbol of hope, a testament to the human capacity for resilience and the power of community to navigate the most daunting of journeys.

"Ethereal Elegance: Butterfly-Inspired Presents to Captivate the Senses"

Butterfly-themed presents hold a captivating allure, seamlessly blending the delicate charm of nature's winged wonders with timeless sophistication. These enchanting offerings cater to those who appreciate the beauty of the natural world, becoming cherished keepsakes that infuse spaces with a sense of wonder.

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From delicate jewelry pieces featuring intricate butterfly motifs to whimsical home accents that flutter with grace, these presents transcend the boundaries of mere decoration. They serve as touchstones, evoking cherished memories and fostering a deeper connection to the fragile yet resilient cycle of life.

In the embrace of the butterfly, these presents become a celebration of the ethereal elegance that permeates the human experience. They are gifts that capture the essence of transformation, serving as reminders that even in the face of adversity, beauty and resilience can emerge, like the butterfly's graceful metamorphosis.

Buy now

These butterfly-inspired presents are not merely objects, but embodiments of the profound truths that lie at the heart of the human journey.

[b2bbusiness]

Amyloidosis Clinical Trial Analysis: Advancing Treatment and Patient Care

Amyloidosis is a rare, potentially life-threatening condition characterized by the abnormal accumulation of amyloid proteins in tissues and organs. The complexity of amyloidosis, with its various subtypes and clinical manifestations, makes it a challenging disease to diagnose and treat. Clinical trials play a crucial role in advancing our understanding of this disease and in developing new treatment strategies. This article provides an in-depth analysis of recent amyloidosis clinical trials, their outcomes, and the implications for patient care.

Understanding Amyloidosis and Its Impact

Amyloidosis is a group of diseases where misfolded proteins form amyloid fibrils, leading to organ dysfunction. The most common types include AL amyloidosis, AA amyloidosis, and hereditary forms like ATTR amyloidosis. Symptoms vary depending on the organs involved, which can include the heart, kidneys, liver, and nervous system. Due to its rarity, amyloidosis is often diagnosed late, leading to poor prognosis. However, ongoing clinical trials are paving the way for early detection and more effective treatments.

Key Objectives of Amyloidosis Clinical Trials

Clinical trials in amyloidosis typically aim to:

Evaluate New Treatments: Testing the efficacy and safety of novel therapies, including small molecules, monoclonal antibodies, and gene-silencing drugs.

Improve Diagnostic Tools: Developing biomarkers and imaging techniques to detect amyloidosis earlier and more accurately.

Enhance Patient Outcomes: Understanding the long-term effects of treatments on quality of life and survival rates.

Recent Breakthroughs in Amyloidosis Clinical Trials

Patisiran and Inotersen in Hereditary ATTR Amyloidosis Patisiran and Inotersen are groundbreaking therapies that target the genetic cause of hereditary ATTR amyloidosis. Recent trials have shown that both drugs significantly reduce the production of TTR protein, thereby slowing disease progression and improving patient outcomes. These therapies represent a major advancement in treating a condition that previously had limited options.

Daratumumab in AL Amyloidosis Daratumumab, a monoclonal antibody initially used in multiple myeloma, has shown promise in treating AL amyloidosis. Clinical trials have demonstrated that Daratumumab can reduce amyloid deposits and improve organ function, particularly in patients who do not respond to traditional chemotherapy.

CRISPR-Cas9 Gene Editing The application of CRISPR-Cas9 technology in amyloidosis is an exciting development. Early-stage trials are exploring its potential to correct genetic mutations responsible for hereditary amyloidosis. While still in its infancy, this approach could lead to curative therapies in the future.

Challenges in Amyloidosis Clinical Trials

Despite the progress, several challenges remain in amyloidosis research:

Patient Recruitment: Due to the rarity of the disease, finding enough participants for clinical trials can be difficult.

Heterogeneity of the Disease: Amyloidosis varies greatly between patients, complicating the design and interpretation of clinical trials.

Long-term Follow-up: Given the chronic nature of the disease, long-term studies are essential to assess the enduring effects of new therapies, which can be resource-intensive.

The Future of Amyloidosis Treatment

The landscape of amyloidosis treatment is rapidly evolving, thanks to ongoing clinical trials. The future holds promise with potential curative approaches, particularly in hereditary forms of the disease. Increased collaboration between research institutions, pharmaceutical companies, and patient advocacy groups is essential to continue driving progress.

Buy the Full Report for More Regional Insights into the Amyloidosis Clinical Trials Download a Free Sample Report

[didanawisgi]

Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2

Abstract

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic and has inflicted enormous damage on the lives of the people and economy of many countries worldwide. However, therapeutic agents against SARS-CoV-2 remain unclear. SARS-CoV-2 has a spike protein (S protein), and cleavage of the S protein is essential for viral entry. Nattokinase is produced by Bacillus subtilis var. natto and is beneficial to human health. In this study, we examined the effect of nattokinase on the S protein of SARS-CoV-2. When cell lysates transfected with S protein were incubated with nattokinase, the S protein was degraded in a dose- and time-dependent manner. Immunofluorescence analysis showed that S protein on the cell surface was degraded when nattokinase was added to the culture medium. Thus, our findings suggest that nattokinase exhibits potential for the inhibition of SARS-CoV-2 infection via S protein degradation.

[healthcareporium]

Hereditary Transthyretin Amyloidosis (hATTR) is a rare, progressive, and life-threatening genetic disorder caused by mutations in the transthyretin (TTR) gene.

[vasanthasworld]

Amyloidosis Pathology Short And Long Essay Question And Answers

[myacare]

It is well-documented that protein metabolism declines throughout the aging process, and this has several consequences for overall health. Of these, stiffening of the heart is a common condition, yet one of the least diagnosed. Varying degrees of cardiac amyloidosis are likely to form part of the aging process and may predispose some individuals to heart failure.

The article below places stiff heart syndrome in the spotlight, addressing what it is, common symptoms, causes, and mechanisms, as well as how to best prevent and treat the condition.

[neha24blog]

Transthyretin Amyloidosis Treatment Market Segment Analysis By Type, Therapy, Disease Type, Distribution Channel, Region And Forecast Till 2030: Grand View Research Inc.

San Francisco, 24 Aug 2023: The Report Transthyretin Amyloidosis Treatment Market Size, Share & Trends Analysis Report By Type (ATTR-PN, ATTR-CM), By Therapy, By Disease Type, By Distribution Channel, By Region, And Segment Forecasts, 2022 – 2030 The global transthyretin amyloidosis treatment market size is expected to reach USD 9.17 billion by 2030, according to a new report by Grand View…