Publications by authors named "Kasthuri R"

Potential and emerging therapeutics for HHT.

Hematology Am Soc Hematol Educ Program

December 2024

A 64-year-old woman with hereditary hemorrhagic telangiectasia (HHT) characterized by a pathological variant in ACVRL1 presents to the clinic for follow-up. Manifestations of HHT include frequent epistaxis and gastrointestinal bleeding, leading to iron-deficiency anemia. Bevacizumab is initiated, with resolution of the anemia.

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Article Synopsis
  • - Immune thrombotic thrombocytopenic purpura (iTTP) is a serious condition involving low platelet counts due to a deficiency in the enzyme ADAMTS13, often treated with rituximab to prevent relapses.
  • - A study using data from the USTMA registry found that the time without relapse (relapse-free survival or RFS) decreased after each rituximab treatment, particularly for Black patients, suggesting that the effectiveness of the drug diminishes with repeated use.
  • - Both the USTMA registry and a separate cohort from Johns Hopkins and the University of Minnesota indicated that Black patients experience a significantly higher risk of relapse with subsequent rituximab treatments, implying a need
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Introduction: Since the inception of arteriovenous grafts (AVG) as a novel technique, there has been greater emphasis on the assessment of outcomes rather than costs. Gross-costing methods over-simplify vascular access surgery and do not reflect the true costs of the service, preventing accurate cost-effectiveness analysis. The aim of this study is to assess the reporting of procedural costs of arteriovenous access creation in economic analyses of vascular access surgery, and to compare the reported costs of the two most performed procedures - arteriovenous fistula (AVF) and arteriovenous graft (AVG).

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  • Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder that leads to severe nosebleeds and related health issues, primarily affecting patients' quality of life due to iron-deficiency anemia from frequent epistaxis.
  • A study was conducted where 144 participants were given either pomalidomide or a placebo for 24 weeks to assess the drug's effectiveness in reducing nosebleed severity and improving quality of life, with results favoring the pomalidomide group.
  • The results showed that those taking pomalidomide experienced a greater decrease in bleeding scores and improved quality-of-life measures, although there were some additional side effects observed in the pomalidomide group.
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  • - The ACTIV-4c trial examined the effectiveness of apixaban, given for 30 days after hospital discharge from COVID-19, but was halted early due to low rates of death or thromboembolism.
  • - Researchers aimed to find high-risk patients for whom post-discharge blood clot prevention might be beneficial by analyzing various factors like age, ethnicity, and D-dimer levels.
  • - Results showed that the overall occurrence of death and thromboembolism was low, especially in patients under 60, and the study concluded that there was no clear high-risk group that would benefit from additional blood clot prevention measures.
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Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States.

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Plasma kallikrein (PKa) is an important activator of factor XII (FXII) of the contact pathway of coagulation. Several studies have shown that PKa also possesses procoagulant activity independent of FXII, likely through its ability to directly activate FIX. We evaluated the procoagulant activity of PKa using a mouse whole blood (WB) thrombin-generation (TG) assay.

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Background: Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability.

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Article Synopsis
  • * The review will look at how much it costs to create two types of vascular access (AVF and AVG) for kidney patients and whether current NHS cost guidelines are accurate.
  • * Researchers will follow specific rules to gather and analyze data from studies published between 2000 and 2023, checking only those that report costs for these surgeries.
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Background: Cephalic arch stenoses (CAS) occur in near 70% of elbow arteriovenous fistulas. Percutaneous transluminal angioplasty (PTA) remains first-line treatment despite documented stent-grafts (SG) efficacy. The study aim is to report long-term outcomes based on initial treatment of CAS.

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  • The study looked at how using special arteriovenous grafts (ecAVG) can help patients avoid unnecessary procedures and improve their health outcomes.
  • Researchers analyzed data from 295 patients over 8 years and found that the use of these grafts increased a lot while problems like infections and blood clots decreased.
  • The results showed that careful planning and teamwork among doctors and nurses can lead to better results for patients, making the risk of losing the graft much lower over time.
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Introduction: Decisions regarding the optimal vascular access for haemodialysis patients are becoming increasingly complex, and the provision of vascular access is open to variations in systems of care as well as surgical experience and practice. Two main surgical options are recognised: arteriovenous fistula and arteriovenous graft (AVG). All recommendations regarding AVG are based on a limited number of randomised controlled trials (RCTs).

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Background: Patients with suspected or newly diagnosed venous thromboembolism (VTE) are often referred to the emergency department (ED) for management, where anticoagulation is initiated. However, when the patient is judged to be suitable for outpatient management, counseling and follow-up specialty care are frequently suboptimal.

Objectives: To establish an advanced practice provider (APP)-led rapid follow-up clinic to improve transitions of care for patients with newly diagnosed deep vein thrombosis or low-risk pulmonary embolism and to provide continued specialty care and support, including management of complications and medication access issues.

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Article Synopsis
  • - The study aimed to evaluate whether anticoagulation with apixaban is more effective than a placebo in preventing death and thromboembolic complications for patients discharged after being hospitalized with COVID-19.
  • - Conducted across 127 U.S. hospitals from 2021 to 2022, the trial included adults who were hospitalized for more than 48 hours and had no contraindications to anticoagulation.
  • - Results showed no significant difference in the incidence of the main outcome between the apixaban group (2.13%) and the placebo group (2.31%), indicating that extended thromboprophylaxis post-discharge may not provide additional benefits.
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  • Excessive mucocutaneous bleeding (MCB) significantly affects the physical and mental health of individuals living with it, and there's a need for more research on various bleeding disorders.
  • The National Hemophilia Foundation and American Thrombosis and Hemostasis Network are developing a research plan by consulting stakeholders to determine priorities and create specific research questions.
  • Expert working groups identified 38 key research questions focused on MCB biology and different bleeding disorders, emphasizing the importance of collaboration and innovative treatments in future studies.
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Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT.

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C1 inhibitor (C1INH) is a multifunctional serine protease inhibitor that functions as a major negative regulator of several biological pathways, including the contact pathway of blood coagulation. In humans, congenital C1INH deficiency results in a rare episodic bradykinin-mediated swelling disorder called hereditary angioedema (HAE). Patients with C1INH deficiency-associated HAE (C1INH-HAE) have increased circulating markers of activation of coagulation.

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Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008-2021 (n = 74).

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Article Synopsis
  • Doctors studied how to make a type of surgery (ecAVG) better for patients needing dialysis.
  • They found that the size of the vein where a stent (a helpful tube) is placed matters more than the stent size itself.
  • Using a smaller stent that’s not tightly attached to the vein can actually help patients do better over time.
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Hereditary hemorrhagic telangiectasia (HHT) is characterized by arteriovenous malformations and telangiectasia, with primary clinical manifestations of epistaxis and gastrointestinal bleeding and resultant anemia. HHT negatively affects health-related quality of life (HR-QoL); however, existing tools to measure HR-QoL are not HHT specific. Our objective was to develop an HHT-specific HR-QoL (HHT-QoL) instrument and evaluate its performance in a cross-sectional survey of individuals with HHT.

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Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020.

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Diabetes mellitus (DM) is a common metabolic illness defined by hyperglycemia caused by insufficient production or absent of pancreatic insulin, with or without concomitant insulin action impairment. Hence, novel problem-solving approaches for assessing early metabolic diseases, notably insulin resistance, are urgently needed. Screening of natural compounds for drug discovery to combat diabetes is common in modern medical research and development.

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