Use of isavuconazole in mucormycosis: a systematic review.

Background: Mucormycosis is an opportunistic fungal infection which is associated with poor prognosis. Only a few antifungals are available in the arsenal against mucormycosis. The global guidelines for diagnosing and managing mucormycosis recommend high doses of liposomal amphotericin B (LAmB) as the first-line treatment.

Erratum to 'Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress' [Research and Practice in Thrombosis and Haemostasis Volume 8, Issue 4, May 2024, 102432].

[This corrects the article DOI: 10.1016/j.rpth.

Exploring the feasibility of utilizing universal primers in detecting mucormycosis pathogens: An in-silico analysis.

This study aimed to design and evaluate a universal primer for Polymerase Chain Reaction (PCR)- based detection of mucormycosis-causing fungi by targeting their Internal Transcribed Spacer (ITS) sequences. In-silico analysis was conducted to assess primer suitability. Using Clustal Omega and Primer-BLAST, ITS sequences of 32 fungi species causing mucormycosis were aligned and subjected to primer design.

Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field.

Plasma from patients with vaccine-induced immune thrombotic thrombocytopenia displays increased fibrinolytic potential and enhances tissue-type plasminogen activator but not urokinase-mediated plasminogen activation.

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown.

Objectives: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls.

Tranexamic acid for haemostasis and beyond: does dose matter?

Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960's to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation.

Tranexamic acid in a mouse model of cerebral amyloid angiopathy: setting the stage for a novel stroke treatment approach.

Background: Symptomatic intracerebral hemorrhage (sICH) commonly occurs in patients with cerebral amyloid angiopathy (CAA). Amyloid also initiates plasminogen activation and might promote sICH.

Objectives: As amyloid-driven plasmin formation can be blocked by tranexamic acid (TXA), we aimed to evaluate the biodistribution and long-term consequences of TXA on brain amyloid-beta (Aβ) levels, inflammation, and neurologic function in APP/PS1 mice.

Efficacy and safety of co-trimoxazole in eradication phase of melioidosis; systematic review.

Background: Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis.

Mucormycosis-causing fungi in humans: a meta-analysis establishing the phylogenetic relationships using internal transcribed spacer (ITS) sequences.

Mucormycosis is a severe angio-invasive fungal infection caused by mucormycetes, a group of fungi that are ubiquitous in the environment. The incidence of mucormycosis has been surging rapidly due to the global corona virus disease 2019 (COVID-19) pandemic. The complete picture of the causative fungi associated with mucormycosis and their phylogenetic relationships are not well defined.

Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery.

Methods: Patients undergoing lower limb surgery were enrolled into the "Tranexamic Acid in Lower Limb Arthroplasty" (TALLAS) pilot study.

Cerebral Amyloid Angiopathy and the Fibrinolytic System: Is Plasmin a Therapeutic Target?

Cerebral amyloid angiopathy is a devastating cause of intracerebral hemorrhage for which there is no specific secondary stroke prevention treatment. Here we review the current literature regarding cerebral amyloid angiopathy pathophysiology and treatment, as well as what is known of the fibrinolytic pathway and its interaction with amyloid. We postulate that tranexamic acid is a potential secondary stroke prevention treatment agent in sporadic cerebral amyloid angiopathy, although further research is required.

The Fibrinolytic System: Mysteries and Opportunities.

The deposition and removal of fibrin has been the primary role of coagulation and fibrinolysis, respectively. There is also little doubt that these 2 enzyme cascades influence each other given they share the same serine protease family ancestry and changes to 1 arm of the hemostatic pathway would influence the other. The fibrinolytic system in particular has also been known for its capacity to clear various non-fibrin proteins and to activate other enzyme systems, including complement and the contact pathway.

Restarting cataract surgery during the COVID-19 pandemic; a prospective study analysing 30 day outcomes after elective cataract surgery in the United Kingdom.

Background: Cataract is a significant cause of preventable blindness in the United Kingdom and worldwide. Prior to the COVID-19 pandemic, cataract surgery was the most commonly performed operation by the National Health Service in the United Kingdom. The aim of this study is to evaluate the safety of elective cataract surgery performed in the United Kingdom in a COVID-19 free hospital during the COVID-19 pandemic.

Fibrinolysis: A Primordial System Linked to the Immune Response.

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems.

Plasminogen: an enigmatic zymogen.

Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding.

Tranexamic acid rapidly inhibits fibrinolysis, yet transiently enhances plasmin generation in vivo.

Tranexamic acid (TXA) is a lysine analogue that inhibits plasmin generation and has been used for decades as an antifibrinolytic agent to reduce bleeding. Recent reports have indicated that TXA can paradoxically promote plasmin generation. Blood was obtained from 41 cardiac surgical patients randomly assigned to TXA or placebo before start of surgery (preOP), at the end of surgery (EOS), then again on postoperative day 1 (POD-1) as well as POD-3.

Tissue-Type Plasminogen Activator and Tenecteplase-Mediated Increase in Blood Brain Barrier Permeability Involves Cell Intrinsic Complement.

Tissue-type plasminogen activator (t-PA) has been the mainstay of therapeutic thrombolysis for patients with acute ischaemic stroke (AIS). However, t-PA can cause devastating intracerebral hemorrhage. t-PA can also influence the CNS in part by modulation of BBB permeability.

Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.

More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success. We hypothesize that individual patient plasmin potential, as measured by response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early.

Coexistence of mycobacterial infections - Mycobacterium tuberculosis and Mycobacterium leprae - in Sri Lanka: a case series.

Background: Leprosy is one of the oldest mycobacterial infections and tuberculosis is the most common mycobacterial infection with a higher degree of infectivity than leprosy. Although both diseases are prevalent in clusters in developing countries, simultaneous occurrence of them in an individual is a rare entity, even in an endemic setting.

Case Presentation: We describe six cases of tuberculosis and leprosy coinfection: a 57-year-old Sinhalese woman, a 47-year-old Tamil woman, a 72-year-old Tamil man, a 59-year-old Sinhalese man, a 54-year-old Sinhalese man, and a 50-year-old Sinhalese man.

Fibrinolysis and COVID-19: A plasmin paradox.

The COVID-19 pandemic has provided many challenges in the field of thrombosis and hemostasis. Among these is a novel form of coagulopathy that includes exceptionally high levels of D-dimer. D-dimer is a marker of poor prognosis, but does this also imply a causal relationship? These spectacularly raised D-dimer levels may actually signify the failing attempt of the fibrinolytic system to remove fibrin and necrotic tissue from the lung parenchyma, being consumed or overwhelmed in the process.

Disseminated Mycobacterium simiae infection in a patient with adult-onset immunodeficiency due to anti-interferon-gamma antibodies - a case report.

Background: Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature.

Case Presentation: A 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly.

Fibrinolysis and the Immune Response in Trauma.

It has long been known that the fibrinolytic system becomes activated following trauma. At first glance, this is not at all surprising and would appear to be in response to coagulation and the apparent need to remove blood clots and restore blood flow. However, in a bleeding patient, the opposite is what is actually needed.

Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis.

Background: Traumatic brain injury (TBI) is known to promote immunosuppression, making patients more susceptible to infection, yet potentially exerting protective effects by inhibiting central nervous system (CNS) reactivity. Plasmin, the effector protease of the fibrinolytic system, is now recognized for its involvement in modulating immune function.

Objective: To evaluate the effects of plasmin and tranexamic acid (TXA) on the immune response in wild-type and plasminogen-deficient (plg ) mice subjected to TBI.

A seven-year retrospective analysis of patch test data in a cohort of patients with contact dermatitis in Sri Lanka.

Background: Patch testing with a baseline series is a common tool employed when the sensitizing agent in contact dermatitis is unclear. However, for Asian countries, there are no locally validated baseline series to utilize in screening.

Methods: We completed a retrospective analysis of all patients that had undergone patch testing with the European Baseline series, Shoe Series or Comprehensive International Baseline series, over 7 years from 2012 to 2018 in a tertiary care reference dermatology clinic in Sri Lanka to evaluate the suitability of these investigations to identify causes for contact dermatitis in the local study population.